Conditions: Recurrent Kaposi Sarcoma Skin Kaposi Sarcoma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 36
Healthy volunteers: no

Brief summary:
This pilot phase II trial studies how well nelfinavir mesylate works in treating patients with kaposi sarcoma. Nelfinavir mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the efficacy of a therapeutic escalation strategy consisting of standard dose nelfinavir (nelfinavir mesylate), followed by high dose nelfinavir, for the treatment of Kaposi sarcoma (KS) tumor lesions. With 36 evaluable participants, the null hypothesis will be rejected if 11 or more participants respond.

SECONDARY OBJECTIVES:

I. To evaluate the safety of high dose nelfinavir among participants with KS. II. To assess the effect of nelfinavir on Kaposi sarcoma-associated herpesvirus (KSHV) lytic gene expression in tumor tissue.

III. To correlate nelfinavir and the primary active metabolite, M8, concentrations with tumor response, antiviral response, and adverse effects in participants with KS.

IV. To assess the effect of nelfinavir on KSHV copy number in saliva.

TERTIARY OBJECTIVES:

I. To assess the effect of nelfinavir on KSHV copy number in PBMC and plasma. II. To assess the effect of nelfinavir on herpes simplex virus (HSV), cytomegalovirus (CMV) and Epstein-Barr virus (EBV) copy number in saliva.

OUTLINE:

STANDARD DOSE NELFINAVIR MESYLATE: Patients receive standard dose nelfinavir mesylate orally (PO) twice daily (BID) for 4 weeks in the absence of progressive disease (PD). Patients with PD at 4 weeks proceed to high-dose nelfinavir mesylate. At week 8, if there is stable disease (SD) or partial response (PR), patients advance to high-dose nelfinavir mesylate. Patients discontinue standard dose nelfinavir mesylate 4 weeks after documentation of complete response (CR).

HIGH DOSE NELFINAVIR MESYLATE: Patients with PD continue to receive high-dose nelfinavir mesylate PO BID for 4 more weeks. If there is PD documented after 4 weeks at the high dose level, nelfinavir mesylate is discontinued. If there is SD or PR, patients continue receiving nelfinavir mesylate for 16 weeks. If there is CR, patients discontinue high-dose nelfinavir mesylate 4 weeks after documentation of CR.

After completion of study treatment, patients are followed up at 8 weeks.

Arms:
arm 1: DOSE NELFINAVIR MESYLATE: Patients receive standard dose nelfinavir mesylate PO BID for 4 weeks in the absence of PD. Patients with PD at 4 weeks proceed to high-dose nelfinavir. At week 8, if there is SD or PR, patients advance to high-dose nelfinavir mesylate. Patients discontinue standard dose nelfinavir mesylate 4 weeks after documentation of CR.

HIGH DOSE NELFINAVIR MESYLATE: Patients with PD continue to receive high-dose nelfinavir mesylate PO BID for 4 more weeks. If there is PD documented after 4 weeks at the high dose level, nelfinavir is discontinued. If there is SD or PR, patients continue receiving nelfinavir mesylate for 16 weeks. If there is CR, patients discontinue high-dose nelfinavir mesylate 4 weeks after documentation of CR.

Interventions: intervention 1: Laboratory Biomarker Analysis intervention 2: Nelfinavir Mesylate
Intervention descriptions: intervention 1: Correlative studies intervention 2: Given PO

Protocol document:
Prot_SAP_ICF_000.pdf: 
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SUMMARY OF CHANGES 
A Pilot Study of Nelfinavir for the Treatment of Kaposi Sarcoma 
Version 4.0 
 
NCI Protocol #: AMC-098 
Local Protocol #: AMC-098 
 
NCI Version Date: 08DEC2020 
Protocol Date: 08DEC2020 
 
I. 
Scientific and Substantive Changes: 
# 
Section 
Comments 
1.  
4.5 
5.1 
5.1.2 
The protocol was updated to clarify that participants who experience a 
cumulative dose delay of > 14 days throughout the course of the trial 
must discontinue study drug. 
2.  
7.2 
Drug dispensing procedures have been revised to comply with Pfizer 
policy. Pharmacists are no longer permitted to break bottles and must 
dispense nelfinavir in the original container, destroying any nelfinavir 
removed from the bottle prior to dispensing. Additionally, pharmacists 
must only supply enough nelfinavir to last the participant until the 
subsequent study visit. Instructions for documenting dispensed 
nelfinavir via DARF have also been included, and requirements for US 
sites to complete a separate DARF documenting drug accountability for 
each protocol using nelfinavir has been removed as sites are permitted 
document using a single DARF. 
 
In addition, locally sourced supplies of FDA-approved Viracept® 
(nelfinavir mesylate) 625 mg tablets may be sourced by the clinical site 
and reimbursed by the AMC with prior approval from the AMC 
ODMC, as permitted by the AMC Executive Committee. 
3.  
8.1.12.2 
Appendix X 
Prolonged storage in formalin may affect biopsy tissue specimen 
viability and result in the inability to perform immunohistochemistry 
(IHC) studies. To ensure specimen viability, the protocol has been 
updated to require that tissue for ICH studies be processed locally to a 
FFPE block and shipped at ambient temperature to the AMC 
Biorepository. Centers are instructed to refer to the MOP for processing 
requirements. If the previously submitted baseline tissue samples are 
inadequate to perform IHC studies, 6 additional slides from the 
diagnostic punch biopsy will be requested. 
4.  
8.4.1 
The window for post-treatment follow up has been revised to permit 
evaluations earlier than 8 weeks post treatment discontinuation, if in the 


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Comments 
opinion of the treating investigator the participant needs to begin 
alternative therapy sooner. All participants must complete the follow 
up evaluations prior to starting alternative therapy. 
5.  
9.0 
This section has been revised to allow CTEP-registered physician 
investigators and CTEP-registered advanced practice clinicians who are 
non-physician investigators (i.e., NP or PA) to perform toxicity 
assessment per local licensure requirements. Delegation of these tasks 
must be recorded on the institution’s AMC delegation of task log (DTL) 
or local equivalent. 
6.  
Appendix XI 
Sulfamethoxazole and trimethoprim (Bactrim) have been removed 
from Appendix XI as drugs that may potentially interact with nelfinavir, 
as there is limited scientific evidence suggesting potential interactions. 
Clinically, Bactrim and nelfinavir are often taken concurrently when 
nelfinavir is the primary ART regimen. 
 
II. 
Administrative and Editorial Changes: 
# 
Section 
Comments 
7.  
Global 
Version number and version date has been updated from v3.0 / 
13FEB2019 to v4.0 / 08DEC2020. 
8.  
Global 
Grammar and spelling have been updated throughout. 
9.  
Title Page 
CTEP IVR numbers have been added for the chairs/co-chairs. 
10. 
Protocol 
Roster 
The protocol roster has been updated to accurately reflect investigator 
qualifications, credentials, address/contact information, and titles. In 
addition, amipm@emmes.com has replaced amcpm@emmes.com as 
the contact email for AMC ODMC. 
11. 
Protocol 
Schema 
10.1 
Phrasing that the study will need to enroll 18 HIV positive and 18 HIV 
negative participants to achieve sufficient power when completing the 
primary analysis has been removed from Section 10.1. and the protocol 
schema has been revised to indicate approximately 18 participants HIV 
positive and 18 HIV negative participants will be enrolled. These 
updates were made for consistency throughout the protocol as the 
enrollment of 18 HIV positive and 18 HIV negative participants is the 
enrollment goal (see “Population” under the Protocol Synopsis).  
12. 
2.4.2 
Protocol references to the Michelle Rudek Lab have been replaced with 
the AMC core lab title, the AMC Pharmacology Core Lab at Johns 
Hopkins University (Lab PI: Michelle Rudek). 
13. 
3.1.2 
Eligibility requirements for documenting HIV-1 negative status have 


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Section 
Comments 
been clarified. A negative result on any of the nationally approved tests 
(including rapid tests) is sufficient to satisfy inclusion the criterion. 
14. 
3.5 
This section has been updated to reflect that enrollment is now open to 
international centers, provided that the site satisfies all regulatory and 
site activation requirements. 
15. 
List of 
Abbreviations 
8.1.10 
8.2.5 
8.3.1.3 
8.4.1.3 
Appendix I 
The individual chemistry tests required throughout the course of the 
study (based on a typical U.S. chemistry panel) and timepoints for 
collection were clarified. CBCs and chemistries performed for 
eligibility must be completed within 4 weeks prior to enrollment, while 
baseline/screening chemistries must be collected within 4 weeks prior 
to starting treatment. Select chemistries have been added to the List of 
Abbreviations. 
16. 
8.1.12.3 
8.2.8.3 
Blood collections for PK analysis have been removed from the 
baseline/screening evaluations, as the first timepoint of collection is 
included in the during treatment evaluations per Section 8.2.8.3 and 
Appendix II. 
17. 
8.2.8.3 
Appendix II 
Appendix IX 
Added clarification that blood collection for PKs may occur within 3 
days before dose administration (i.e., - 3 day window), and listed the 
cycle numbers corresponding to the study week. 
18. 
8.3.1.2 
8.4.1.2 
The requirement that KS tumor assessments must be completed at each 
study visit (every 2 weeks) and at the early treatment discontinuation 
and follow-up visits has been clarified. Because there is only one early 
treatment discontinuation visit and one follow-up visit, KS response 
assessment will only be completed once for each timepoint. 
19. 
12.4 
12.5 
CTEP registration procedures for the investigator, research associate, 
and for site participation have been added to align with the CTEP 
template and to require that the AMC DTL must be updated 
contemporaneously as personnel are added or removed and/or study 
roles and delegated tasks change. Changes must be approved by the CI, 
and documented by his/her initials and date, before they are 
implemented. 
20. 
Appendix II 
Specimen handling instructions for IHC studies has been replaced with 
a reference/link to Appendix X. 
21. 
Appendix VI 
The AMC Data and Safety Monitoring plan was updated from version 
6.0 to the current version (9.0). Key revisions include the addition of an 
introduction to address the variety of systems the AMC uses for 
individual trials, changes to the data entry systems used by some AMC 
trials (OPEN/Rave), participation with NCI CIRB for new AMC 
protocols, procedures for data reporting, administrative changes 


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(updates to document organization, external links, and group 
terminology), and to state that the IRB review plan is identified in the 
protocol, as the AMC is opening international studies subject to 
review/requirements per their respective regions. 
22. 
Appendix VII 
The study diary was reorganized for clarity. “Capsules” were updated 
to “tablets.” 
23. 
Appendix X 
This Appendix has been updated to indicate that RNAlater for gene 
expression profiling may be sourced locally or provided by the AMC. 


 
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AIDS MALIGNANCY CONSORTIUM 
 
AMC PROTOCOL #098 
A Pilot Study of Nelfinavir for the Treatment of Kaposi Sarcoma 
A Trial of the AIDS Malignancy Consortium (AMC) 
 
Sponsored by: 
National Cancer Institute 
Office of HIV and AIDS Malignancy (OHAM) 
 
NCT Registration Number: 
NCT03077451 
 
Pharmaceutical Support 
Provided by: 
Pfizer Inc. 
IND Status: Exempt 
 
Commercially Available 
Agents:  
Viracept® (nelfinavir mesylate) 
NSC #: 722664 
 
Protocol Chair: 
Soren Gantt, MD, PhD (IVR-47912) 
 
Protocol Co-Chairs: 
Rich Ambinder, MD (IVR-10686) 
Rachel Bender Ignacio, MD, MPH (IVR-609501) 
Warren Phipps, MD, MPH (IVR-615161) 
Version 4.0, 08DEC20202 
NCI Version Date 08DEC2020 
 


 
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AMC PROTOCOL SIGNATURE PAGE 
I, ____________________, Principal Investigator at site ________, agree to conduct and follow 
this protocol: AMC Protocol # 098 – A Pilot Study of Nelfinavir for the Treatment of Kaposi 
Sarcoma (Version 4.0, 08DEC2020), as written according to AMC, NCI, and FDA guidelines. I 
understand that no deviations from the protocol eligibility criteria or waivers for protocol 
deviations will be permitted. 
 
 
_________________________________ 
 
______________________ 
PI Signature 
Date (DDMMMYYYY) 


 
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TABLE OF CONTENTS 
SUMMARY OF CHANGES ......................................................................................................... i 
I. 
Scientific and Substantive Changes: ........................................................................... i 
II. 
Administrative and Editorial Changes: ...................................................................... ii 
AMC PROTOCOL SIGNATURE PAGE .................................................................................. 2 
TABLE OF CONTENTS ............................................................................................................. 3 
PROTOCOL ROSTER ................................................................................................................ 6 
PROTOCOL SYNOPSIS ............................................................................................................. 8 
PROTOCOL SCHEMA ............................................................................................................... 9 
LIST OF ABBREVIATIONS .................................................................................................... 10 
1.0 
OBJECTIVES ................................................................................................................. 12 
1.1 Primary Objective .................................................................................................... 12 
1.2 Secondary Objectives ............................................................................................... 12 
1.3 Exploratory Objectives ............................................................................................ 12 
2.0 
BACKGROUND ............................................................................................................. 13 
2.1 Study Disease ........................................................................................................... 13 
2.2 Study Agent ............................................................................................................. 14 
2.3 Study Design and Rationale ..................................................................................... 15 
2.4 Correlative Studies ................................................................................................... 17 
3.0 
PARTICIPANT SELECTION ...................................................................................... 19 
3.1 Eligibility Criteria .................................................................................................... 19 
3.2 Exclusion Criteria .................................................................................................... 21 
3.3 Number of Participants to be Enrolled ..................................................................... 23 
3.4 Participant Enrollment Procedures .......................................................................... 23 
3.5 Enrollment at International Sites ............................................................................. 24 
4.0 
TREATMENT PLAN ..................................................................................................... 25 
4.1 Agent Administration ............................................................................................... 25 
4.2 General Concomitant Medication and Supportive Care Guidelines ........................ 26 
4.3 Duration of Therapy ................................................................................................. 26 
4.4 Duration of Follow Up ............................................................................................. 26 
4.5 Criteria for Removal from Treatment ...................................................................... 26 
5.0 
DOSING DELAYS/DOSE MODIFICATIONS ........................................................... 28 
5.1 Dose Modifications for Nelfinavir ........................................................................... 28 
6.0 
ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS ...................... 32 


 
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6.1 Comprehensive Adverse Events and Potential Risks Lists...................................... 32 
6.2 Classification of AEs by Severity and Relationship to Study Drug Administration 32 
6.3 Expedited Adverse Event Reporting ........................................................................ 33 
6.4 Routine Adverse Event Reporting ........................................................................... 36 
6.5 Secondary Malignancy ............................................................................................. 36 
6.6 Second Malignancy .................................................................................................. 36 
7.0 
PHARMACEUTICAL INFORMATION ..................................................................... 37 
7.1 Nelfinavir (Viracept®, nelfinavir mesylate) ............................................................. 37 
7.2 Drug Orders, Transfers, Returns, and Accountability ............................................. 39 
8.0 
CLINICAL AND LABORATORY EVALUATIONS ................................................. 41 
8.1 Screening/Baseline Evaluations ............................................................................... 41 
8.2 Evaluations during Treatment .................................................................................. 42 
8.3 Early Treatment Discontinuation Evaluations ......................................................... 43 
8.4 Follow-up Evaluations ............................................................................................. 44 
8.5 Final Evaluations, Off Study .................................................................................... 44 
9.0 
MEASUREMENT OF EFFECT ................................................................................... 45 
9.1 Definition of Response ............................................................................................ 45 
10.0 
STATISTICAL CONSIDERATIONS .......................................................................... 48 
10.1 Study Design/Endpoints........................................................................................... 48 
10.2 Sample Size/Accrual Rate ........................................................................................ 50 
10.3 Reporting and Exclusions ........................................................................................ 50 
10.4 Stopping Rule for Feasibility ................................................................................... 51 
11.0 
ROLE OF DATA MANAGEMENT ............................................................................. 52 
11.1 CRF Instructions ...................................................................................................... 52 
11.2 Data Quality ............................................................................................................. 52 
11.3 Data Monitoring ....................................................................................................... 52 
12.0 
ETHICAL AND REGULATORY CONSIDERATIONS ........................................... 53 
12.1 IRB Approval and Informed Consent ...................................................................... 53 
12.2 Changes to the Protocol ........................................................................................... 53 
12.3 Women and Minorities ............................................................................................ 53 
12.4 Investigator and Research Associate Registration with CTEP ................................ 55 
12.5 Protocol Registration and Delegation of Tasks Log ................................................ 56 
13.0 
REFERENCES ................................................................................................................ 57 
APPENDIX I: SCHEDULE OF PROCEDURES .................................................................... 61 


 
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APPENDIX II: BIOMARKERS AND CORRELATIVE STUDIES ..................................... 64 
APPENDIX III: PERFORMANCE STATUS SCALES ......................................................... 65 
APPENDIX IV: AIDS AND CANCER SPECIMEN RESOURCE (ACSR) SPECIMEN 
PREPARATION AND SHIPPING INSTRUCTIONS ............................................................ 66 
APPENDIX V: ACSR INFORMED CONSENT ..................................................................... 69 
APPENDIX VI: AMC DATA AND SAFETY MONITORING PLAN ................................. 74 
APPENDIX VII: PARTICIPANT DRUG DIARY .................................................................. 79 
APPENDIX VIII: CENTRAL PATHOLOGY REVIEW ....................................................... 82 
APPENDIX IX: SPECIMEN PREPARATION AND SHIPPING INSTRUCTIONS FOR 
NELFINAVIR AND METABOLITE PHARMACOKINETIC STUDIES ........................... 83 
APPENDIX X: AMC BIOREPOSITORY SPECIMEN PREPARATION AND SHIPPING 
INSTRUCTIONS FOR CORRELATIVE STUDIES .............................................................. 85 
APPENDIX XI: DRUGS KNOWN TO BE METABOLIZED BY SELECTED CYP450 
ISOENZYMES ............................................................................................................................ 93 
APPENDIX XII: DRUGS KNOWN OR SUSPECTED TO INHIBIT KSHV REPLICATION
....................................................................................................................................................... 99 
APPENDIX XIII: PARTICIPANT INSTRUCTIONS FOR ORAL SWABS ..................... 100 
APPENDIX XIV: PARTICIPANT DRUG INFORMATION HANDOUT AND WALLET 
CARD ......................................................................................................................................... 103 


 
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PROTOCOL ROSTER 
AMC Protocol # 098 
A Pilot Study of Nelfinavir for the Treatment of Kaposi Sarcoma 
 
Protocol Chair: 
Soren Gantt, MD, PhD 
Centre de recherche du CHU Sainte-Justine 
3175 Côte Sainte-Catherine 
Montréal Qc H3T 1C5 
Canada 
Tel: (514) 345-4931 
Email:soren.gantt.hsj@ssss.gouv.qc.ca 
Protocol Statistician: 
Jeannette Lee, PhD 
Department of Biostatistics 
University of Arkansas for Medical Sciences 
4301 West Markham Street, #781, Ed III, 
Room 3212 
Little Rock, AR 72205 
Tel: (501) 526-6712 
Fax: (501) 526-6729 
Email: jylee@uams.edu 
Protocol Co-Chair: 
Rich Ambinder, MD 
Johns Hopkins University Oncology Center 
Bunting-Blaustein Cancer Research Bldg. 
1650 Orleans Street, Room 389 
Baltimore, MD 21231 
Tel: (410) 955-8839 
Fax: (410) 955-0960 
Email: ambinri@jhmi.edu 
AMC Data Management/Operations: 
AMC Operations and Data Management 
Center 
The Emmes Company, LLC 
401 N. Washington Street, Suite 700 
Rockville, MD 20850 
Tel: (301) 251-1161 
Fax: (240) 238-2842 
Email: amipm@emmes.com 
Protocol Co-Chair: 
Rachel Bender Ignacio, MD, MPH 
1100 Fairview Ave N Mailstop E2-112 
Fred Hutchinson Cancer Research Center 
Seattle, WA 98109 
Tel: (206) 667-4628 
Fax: (206) 667-6366 
Email: rbenderi@fredhutch.org 
 
AMC Biorepository Director: 
Sylvia Silver, DA 
George Washington University Medical 
Center 
2300 I Street, NW 
Ross Hall, Room 118 
Washington, DC 20037 
Tel: (202) 994-2945 
Fax: (202) 994-5056 
Email: ssilver@gwu.edu 
Protocol Co-Chair: 
Warren Phipps, MD, MPH 
Fred Hutchinson Cancer Research Center 
1100 Fairview Ave. N., 
M1-B140 
Seattle, WA 98109 
Tel: (206) 667-4600 
Email: wtphipps@fredhutch.org 
 
 
 


 
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AMC Kaposi Sarcoma Working Group 
Chair: 
Lee Ratner, MD, PhD 
Washington University School of Medicine 
Division of Oncology 
660 S. Euclid Avenue 
Campus Box 8069 
St. Louis, MO 63110 
Tel: (314) 362-8836 
Fax: (314) 747-2120 
Email: lratner@dom.wustl.edu 
 
AMC Core Laboratory Director: 
: 
Jeffrey Bethony, PhD 
George Washington University Medical 
Center 
2300 I Street NW 
Washington, DC 20037 
Tel: (202) 590-8342 
Fax: (202) 994-5056 
Email: jbethony@gwu.edu 
AMC Pharmacologist: 
Michelle A. Rudek, PharmD, PhD 
Analytical Pharmacology Core Laboratory 
Johns Hopkins Oncology Center 
Bunting-Blaustein Cancer Research Bldg. 
1650 Orleans Street, Room 1M52 
Baltimore, MD 21287 
Tel: (410) 614-6321 
Fax: (410) 502-0896 
Email: mrudek2@jhmi.edu 
Sub-Saharan Africa AMC Biorepository 
Director: 
Johann Schneider, MMed Anat Path 
Division of Anatomical Pathology 
National Health Laboratory Service 
10th Floor Green Avenue, Room 52 
Tygerberg Hospital 
Tygerberg 
7535 South Africa 
Tel: 27-21-938-4041 
Fax: 27-21-938-6559 
Email: jws2@sun.ac.za 
 
AMC Pathology Core Laboratory: 
Ethel Cesarman, MD, PhD 
Weill Medical College of Cornell University 
Department of Pathology 
1300 York Avenue, Room C410 
New York, NY 10065 
Tel: (212) 746-8838 
Fax: (212) 746-4483 
Email: ecesarm@med.cornell.edu 
Uganda Cancer Institute Local PI: 
Jackson Orem, MBChB, MMed, PhD 
Uganda Cancer Institute 
P.O. Box 3935 
Kampala, Uganda 
Tel: +256 414 540605/680467 
Mobile: +256 782 320543 
Fax: +256 414 540410 
Email: jacksonorem@yahoo.co.uk 
 


 
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PROTOCOL SYNOPSIS 
Title: 
A Pilot Study of Nelfinavir for the Treatment of Kaposi Sarcoma 
Phase of Study: 
Phase II  
Participating Institutions: 
This protocol will be open to all AMC domestic member sites and 
AMC sub-Saharan Africa sites. 
Accrual Target: 
36 participants  
Population: 
Participants with Kaposi sarcoma (KS). Enrollment will target 
but will not be limited to 18 participants with HIV infection and 
18 without HIV infection. 
Regimen: 
Nelfinavir 1250 mg twice daily for up to 8 weeks, followed by 
escalation to nelfinavir 3125 mg twice daily for up to 16 weeks 
(up to 24 weeks of treatment). Participants will be followed for 
up to 8 weeks following treatment discontinuation. 
Anticipated Trial 
Duration: 
Up to 3 years 
Primary Objective: 
To determine the efficacy of a therapeutic escalation strategy 
consisting of standard dose nelfinavir, followed by high dose 
nelfinavir, for the treatment of KS tumor lesions. 
Secondary Objectives: 
1. To evaluate the safety of high dose nelfinavir among 
participants with KS. 
2. To assess the effect of nelfinavir on Kaposi sarcoma-
associated herpesvirus (KSHV) lytic gene expression in 
tumor tissue. 
3. To correlate nelfinavir and the primary active metabolite, M8, 
concentrations with tumor response, antiviral response, and 
adverse effects in participants with KS. 
4. To assess the effect of nelfinavir on KSHV copy number in 
saliva. 
Exploratory Objectives: 
1. To assess the effect of nelfinavir on KSHV and Epstein-Barr 
virus (EBV) copy number in peripheral blood mononuclear 
cells (PBMC) and plasma. 
2. To assess the effect of nelfinavir on herpes simplex virus 
(HSV), cytomegalovirus (CMV), and EBV copy number in 
saliva. 


 
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PROTOCOL SCHEMA 
 
 
 
 
Standard dose nelfinavir, (1250 mg twice daily); high dose nelfinavir, (3125 mg twice daily); PD, 
progressive disease; CR, complete response; SD, stable disease; PR, partial response. 
Baseline viral measurements 
for 2 weeks 
Standard dose nelfinavir 
High dose nelfinavir 
Stop nelfinavir 4 weeks 
after CR 
Stop nelfinavir 
PD after 4 weeks 
or SD/PR at 
8 weeks 
CR at any time 
SD/PR: continue 
for up to16 
weeks 
CR at any time 
Stop nelfinavir 
4 weeks after CR 
Approximately 18 
HIV-positive persons 
Approximately 18 
HIV-negative persons 
PD after 
4 weeks 


 
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LIST OF ABBREVIATIONS 
ACSR ................................................................................... AIDS and Cancer Specimen Resource 
ACTG .................................................................................................... AIDS Clinical Trials Group 
AE ................................................................................................................................ adverse event 
AIDS .................................................................................. Acquired Immunodeficiency Syndrome 
ALT (SGPT) .................................................................................................... alanine transaminase 
AMC ................................................................................................ AIDS Malignancy Consortium 
ART.................................................................................................................. antiretroviral therapy 
AST (SGOT) ................................................................................................. aspartate transaminase 
AUC .................................................................................................................. area under the curve 
BID ................................................................................................................ bis in die (twice a day) 
BUN ................................................................................................................... blood urea nitrogen 
CBC................................................................................................................. complete blood count 
CDC ............................................................................. Centers for Disease Control and Prevention 
CDUS .................................................................................................. Clinical Data Update System 
CMV ....................................................................................................................... cytomegalovirus 
CO2 ............................................................................................................................ carbon dioxide 
CR ........................................................................................................................ complete response 
CRF ......................................................................................................................... case report form 
CTCAE ............................................................ Common Terminology Criteria for Adverse Events 
CTEP ....................................................................................... Cancer Therapy Evaluation Program 
CTEP-AERS ..................................................................... CTEP Adverse Event Reporting System 
DARF ......................................................................................... Drug Accountability Record Form 
DHHS ............................................................................ Department of Health and Human Services 
DLT ................................................................................................................. dose-limiting toxicity 
DNA ............................................................................................................... deoxyribonucleic acid 
DSMB ............................................................................................... Data Safety Monitoring Board 
EBV..................................................................................................................... Epstein-Barr Virus 
EIACD ................................................................................. enzyme inducing anti-convulsant drug 
EKG ..................................................................................................................... electrocardiogram 
ELISA .................................................................................... enzyme-linked immunosorbent assay 
ER ................................................................................................................. endoplasmic reticulum 
FIAU ................................................................................................................................. fialuridine 
FDA.................................................................................................. Food and Drug Administration 
GEE ............................................................................................... generalized estimating equations 
HD-NFV ............................................................................................................high dose nelfinavir 
HHV-8.............................................................................................................. human herpesvirus-8 
HIV ............................................................................................... Human Immunodeficiency Virus 
HSV.................................................................................................................. herpes simplex virus 


 
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IDB ....................................................................................................... Investigational Drug Branch 
IHC ................................................................................................................ immunohistochemistry 
IRB ........................................................................................................... institutional review board 
KS ............................................................................................................................ Kaposi sarcoma 
KSHV .................................................................................. Kaposi sarcoma-associated herpesvirus 
LANA ......................................................................................... latency-associated nuclear antigen 
MMP2 ........................................................................................................ matrix metalloprotease 2 
MOP ................................................................................................................ manual of procedures 
MTD ........................................................................................................... maximum tolerated dose 
NCI ............................................................................................................ National Cancer Institute 
NCT............................................................................................. National Clinical Trials [Registry] 
NFV.................................................................................................................................... nelfinavir 
NIH ...................................................................................................... National Institutes of Health 
NRTI .............................................................. nucleoside/nucleotide reverse transcriptase inhibitor 
NNRTI ...................................................................... non-nucleoside reverse transcriptase inhibitor 
ODMC............................................................................. Operations and Data Management Center 
OHAM ......................................................................................... Office of HIV AIDS Malignancy 
PBMC ....................................................................................... peripheral blood mononuclear cells 
PD… ...................................................................................................................progressive disease 
PI ........................................................................................................................... protease inhibitor 
PIO ........................................................................................................ Protocol Information Office 
PK ......................................................................................................................... pharmacokinetics 
PR ............................................................................................................................. partial response 
qPCR .................................................................................... quantitative polymerase chain reaction 
RNA ..................................................................................................................... ribose nucleic acid 
SAE ................................................................................................................. serious adverse event 
SD ................................................................................................................................ stable disease 
SD-NFV ...................................................................................................... standard dose nelfinavir 
SOC ......................................................................................................................system organ class 
SOP ..................................................................................................... standard operating procedure 
SUSAR ..................................................... serious and unexpected suspected adverse drug reaction 
ULN ................................................................................................................ upper limit of normal 


 
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1.0 
OBJECTIVES 
1.1 
Primary Objective 
To determine the efficacy of a therapeutic escalation strategy consisting of standard dose 
nelfinavir, followed by high dose nelfinavir, for the treatment of Kaposi sarcoma tumor 
lesions. 
1.2 
Secondary Objectives 
1.2.1 To evaluate the safety of high dose nelfinavir among participants with KS. 
1.2.2 To assess the effect of nelfinavir on KSHV lytic gene expression in tumor tissue. 
1.2.3 To correlate nelfinavir and the primary active metabolite, M8, concentrations with 
tumor response, antiviral response, and adverse effects in participants with KS. 
1.2.4 To assess the effect of nelfinavir on KSHV copy number in saliva. 
1.3 
Exploratory Objectives 
1.3.1 To assess the effect of nelfinavir on KSHV and EBV copy number in PBMC and 
plasma. 
1.3.2 To assess the effect of nelfinavir on HSV, CMV, and EBV copy number in saliva. 


 
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2.0 
BACKGROUND 
2.1 
Study Disease 
Kaposi sarcoma is a vascular inflammatory tumor of endothelial origin caused by Kaposi 
sarcoma-associated herpesvirus, also known as human herpesvirus 8 (HHV-8)1. HIV 
infection and immunosuppression dramatically increase the risk of KS among people 
infected with KSHV. KS is the most common AIDS-defining malignancy. Due to in part 
to the low prevalence of KSHV infection, KS is rare among HIV-uninfected individuals in 
the U.S. However, in parts of East Africa where KSHV is endemic, KS is common among 
people with and without HIV infection2. Like all herpesviruses, HHV-8 infection of cells 
results in one of two discrete viral programs, latency and lytic replication. 
During latent infection, few viral genes are expressed and the HHV-8 genome is 
maintained as an episome. KS tumor (“spindle”) cells are predominately (~99%) latently 
infected with KSHV. However, a portion of spindle cells undergo lytic replication and 
produce virions3-5. Most infected cell types in culture display a progressive loss of the 
HHV-8 episomal genome within 5-10 divisions in the absence of genetic selection or 
reinfection6, such that the KSHV genome is eventually lost from most spindle cell lines 
isolated from KS lesions7-9. This indicates that persistence of KSHV within KS tumors 
requires ongoing lytic replication and infection of new cells6. In addition, numerous lytic 
viral gene products detected in KS tumors appear central to KS pathogenesis. Proteins 
expressed by spindle cells during lytic replication directly or indirectly mediate several 
aspects of KS pathogenesis; including inflammation (vGPCR, vIL-6, K15), angiogenesis 
(vIL-6, vGPCR, K1, vCCL1, vCCL2), cell growth (vIL-6, vGPCR, K1), and inhibition of 
apoptosis (vCCL1, vCCL2, vBcl2, vIRF1, K1), among others10, 11. Of note, lytically 
infected cells are destroyed, and thus, their effects in KS lesions should be limited to either 
increasing the number of infected cells or paracrine effects of lytic viral gene products. 
KSHV DNA is detected more frequently and at higher copy numbers in blood of KS 
patients compared to controls with asymptomatic KSHV infection12-15. A large proportion 
of KSHV DNA in plasma is encapsidated in virions14, 16, indicating an association between 
KS and systemic viral replication and dissemination. KSHV viremia appears to be in the 
causal pathway for KS, rather than a consequence, since KSHV viremia predicts 
subsequent KS in cohorts of asymptomatic people with KSHV and Human 
Immunodeficiency Virus (HIV) co-infection17, 18. In addition, ganciclovir, which inhibits 
KSHV lytic replication, prevents incident KS (see below). Therefore, inhibiting KSHV 
replication may interfere with KS progression. 
A large number of drugs that block herpesvirus DNA synthesis have been reported to 
inhibit HHV-8 replication19-23. Of these agents, ganciclovir (or its oral pro-drug 
valganciclovir) is the only one proven to either suppress HHV-8 replication in vivo or 
prevent the development of KS in randomized trials. In a randomized, placebo-controlled, 
cross-over trial, valganciclovir was shown to reduce HHV-8 oral shedding frequency by 
46% and quantity by 0.44 log copies/mL24. In a randomized trial, Ganciclovir treatment of 
cytomegalovirus retinitis in HIV-infected patients statistically significantly reduced the 
incidence of KS by 75% when given orally and 93% when given intravenously compared 
to intraocular treatment alone25. Numerous observational studies have also suggested that 
ganciclovir and foscarnet, but not acyclovir, may prevent KS26-29. The efficacy of antivirals 


 
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for the treatment, as opposed to prevention, of KS is less clear. Case reports have suggested 
that cidofovir or foscarnet may have improved KS treatment outcomes30-32. However, data 
from small observational studies did not indicate better KS outcomes with inhibitors of 
HHV-8 DNA synthesis33,34. Furthermore, the largest trial of cidofovir to date, which 
included seven patients with KS, found no apparent effect on progression or HHV-8 
viremia35. 
2.2 
Study Agent 
2.2.1 Nelfinavir mesylate (Viracept®) 
Nelfinavir is an orally administered aspartyl-protease inhibitor (PI) approved for 
the treatment of HIV. More recently off-target effects have led investigators to 
repurpose nelfinavir as a potential anticancer agent36-38. Several early phase clinical 
trials have resulted. In a phase I dose escalation trial in lung cancer, nelfinavir was 
studied in combination with combination chemotherapy (cisplatin and 
etoposide)/radiation therapy39. Two dose levels were studied, 625 mg bis in die 
(BID [twice daily]) and 1250 mg BID. No dose limiting toxicities (DLTs) were 
seen at either dose level and there was no grade 3 or 4 diarrhea reported. 
In a National Cancer Institute (NCI) phase I trial in participants with refractory 
solid tumors, 3125 mg BID was found to be the maximum tolerated dose (MTD)40. 
The 3125 mg BID dosing leads to plasma levels of 18 µM. Some participants have 
continued this dose level for more than 18 months. In contrast to the early 
experiences with nelfinavir in the United States, in which secretory diarrhea was 
identified as a common adverse effect41, diarrhea was unusual in this study40. 
Additionally, there were no cumulative toxicities noted, and no participants 
developed greater than grade 2 changes in lipids or fasting glucose, despite 11 
participants receiving the MTD of 3125 mg BID for a median of 6.6 months. Two 
of three participants receiving 3750 mg BID of nelfinavir experienced grade 4 
neutropenia, but the drug was well tolerated at other doses. It should also be noted 
that in previous HIV treatment trials of nelfinavir in Sub-Saharan Africa, the 
frequency with which diarrhea was reported ranged from 2-11% and did not require 
discontinuation of treatment42-45. While non-linearity in the pharmacokinetics was 
noted at doses above 1875 mg, greater than 50% of the patients at 3125 mg had 
higher maximal (Cmax) and total area under the curve (AUC) exposure compared 
with the 1875 mg dose. 
In another phase I study of nelfinavir, for liposarcoma, there were no DLTs at the 
highest evaluated dose of 4250 mg BID46. In that study, episodes of diarrhea 
occurred in a minority of courses, all episodes were mild, and were not associated 
with higher nelfinavir doses. However, there was no measurable increase (and 
perhaps a slight decrease) in the peak plasma levels of nelfinavir or the primary 
active metabolite, M8, between 3000 mg BID and 4250 mg BID, suggesting that 
higher levels may not be achievable, perhaps due to autoinduction of metabolism46. 
Therefore, in this trial of nelfinavir for KS, we will cap the high dose at 3125 mg 
BID and obtain trough levels to account for the potentially large variability in 
nelfinavir exposure. 
 


 
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2.3 
Study Design and Rationale 
The off-target effects of nelfinavir are highly relevant for KS47. Several studies show that 
nelfinavir can inhibit PI3K/Akt signaling and induce endoplasmic reticulum (ER) stress 
with activation of the unfolded protein response38, 48-50. In addition, antiangiogenic effects 
of nelfinavir are well documented, including down regulating hypoxia-inducible factor 1 
alpha (HIF-1-α), VEGF and matrix metalloprotease 2 (MMP2) activity, and inhibition of 
STAT3 signaling and of γ-secretase activity50,51. Nelfinavir has activity against a broad 
range of cancer cell lines and in animal models36,37. These diverse tumors include 
liposarcoma52,53, multiple myeloma48, primary effusion lymphoma and Burkitt lymphoma. 
All of these activities suggest the possibility of a direct antitumor effect in KS. 
In addition, nelfinavir both reactivates lytic KSHV gene expression and inhibits production 
of infectious KSHV in vitro. Consistent with activation of the unfolded protein response, 
nelfinavir activates KSHV lytic gene expression54. Activation of viral lytic gene expression 
might directly result in tumor cell killing as viral replication activates DNA damage 
pathways and apoptosis or might lead to increased viral antigen expression and increased 
susceptibility to immune killing. Although viral lytic gene expression is induced in latently 
infected cells, nelfinavir potently blocks in vitro production of infectious KSHV, and other 
herpesviruses, at concentrations that are achieved in plasma of patients after oral 
administration55. Thus, we hypothesize that nelfinavir will decrease measurable viral loads. 
Protease inhibitor-based antiretroviral therapy (ART) has recently been shown to decrease 
shedding of KSHV, though this study was not able to demonstrate a superior effect of 
nelfinavir compared with other PIs56. In herpes simplex virus 1 (HSV-1), nelfinavir 
prevents envelopment and release of mature virus from infected cells54,57, suggesting that 
that nelfinavir may act similarly against KSHV. Although initial induction of KSHV lytic 
gene expression by nelfinavir might theoretically cause transient exacerbation of KS, 
which we will monitor for, we expect that the combination of antitumor and antiviral 
activities will result in KS responses. 
Proposals to evaluate the effects of nelfinavir on KSHV infection and KS in HIV-infected 
individuals have focused on the potential confounding by the antiretroviral activity of 
nelfinavir; even with adjustment for HIV viral load and CD4 counts, any effect of nelfinavir 
might still be due to enhanced control of HIV infection. By including participants with KS 
but without HIV, we have the ability to definitively examine the direct clinical antitumor 
and antiviral effects of nelfinavir, which may provide valuable clinical information 
regarding the treatment of KS in HIV-negative individuals, as well as those who are HIV-
infected. Additionally, because all prior studies in reducing incident KS or treating KS with 
PIs have focused on ART-naïve persons, it is difficult to compare studies of persons 
receiving modern highly-active ART regimens, that do or do not include PIs, directly for 
their effects on KS and KSHV, because it is known that PIs provide more rapid virologic 
and immunologic responses than triple nucleoside/nucleotide reverse transcriptase 
inhibitor (NRTI) regimens or non-nucleoside reverse transcriptase inhibitor (NNRTI) 
regimens (unclear vs. recently utilized integrase inhibitors). Therefore, in this study, we 
propose to add nelfinavir to stable complete ART regimens in HIV-infected persons and in 
HIV-negative KS participants, in order to remove the HIV virologic and immunologic 
confounding implied in PI use. This is distinct from modern trials, which evaluate cytotoxic 
chemotherapy plus ART-initiation in previously ART-naïve persons. Thus, we expect we 


 
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may see less robust responses in persons with stable disease (SD) despite ongoing ART 
usage58-60. Comparable trials of novel agents, such as valproic acid or VEGF inhibitors in 
persons already on stable ART at enrollment, showed much smaller effect sizes between 
20-30%61-64. 
The proposed trial is based on the hypothesis that nelfinavir might be repurposed as an 
anticancer agent, and that among all cancers that might be targeted, the effects of nelfinavir 
on Akt signaling, angiogenesis pathways, viral gene expression, and infectious virion 
production seem almost tailored to the treatment of KS. And, save for (likely undue) 
concerns about diarrhea, the side effect profile is gentler than for any of the approved 
treatments (paclitaxel, liposomal doxorubicin) or those presently being investigated by the 
AMC (bortezomib, lenalidomide). Therefore, we propose to evaluate a treatment strategy 
of nelfinavir in AIDS-associated and in HIV-negative KS participants to determine tumor 
response and virologic suppression. The strategy starts with standard dose (1250 mg BID) 
nelfinavir to determine whether KS patients may demonstrate a tumor response and to 
determine the antiviral activity of the FDA-approved regimen. Those participants with 
tumor progression or no response to standard dose nelfinavir will receive high dose (3125 
mg BID) nelfinavir therapy, which has been found to be well tolerated in clinical trials of 
cancer patients. In addition to tumor and virologic outcomes, these participants will be 
assessed for the possibility of bone marrow suppression and other toxicities that can occur 
with nelfinavir, especially in combination with a full ART regimen. 
Clinical tumor responses would pave the way for further evaluation of nelfinavir alone as 
an antitumor agent. Given the possibility of activation of viral lytic gene expression, 
evaluation of the combination of nelfinavir with an agent such as ganciclovir or fialuridine 
(FIAU) that would kill infected cells might be pursued. This study will evaluate the safety 
and efficacy of nelfinavir to treat KS. Furthermore, findings regarding the tumor and 
virologic response in participants may provide valuable insights into KS pathogenesis and 
the mechanism(s) of action of nelfinavir, which may translate into knowledge to guide 
therapy of KS worldwide. Finally, if nelfinavir was found to have an antiviral effect on 
KSHV in vivo, the drug may play a role in strategies to prevent the development of KS 
among persons deemed to be at high risk. 
High-Dose Safety Review 
As outlined in Section 3.5, the first three domestic participants on high-dose nelfinavir 
treatment were evaluated for safety on November 29, 2017. In accordance with the 
protocol, the Protocol Chair, AMC Medical Monitor, and Protocol Statistician participated 
in this review, along with the protocol co-chairs. All participants experienced grade 2 or 3 
diarrhea; however, several participants continued treatment during the AE and did not 
report diarrhea until the next visit, and the providers continued treatment with appropriate 
medical management in some cases without holding the dose for resolution to grade 1. No 
other grade 3 adverse events were reported among these participants. Available relevant 
safety data for the other three domestic participants on high-dose nelfinavir was also 
reviewed and did not reflect significant toxicity. The safety review team agreed that the 
safety data for AMC-098 does not reflect significant toxicities or toxicity that requires 
supportive care exceeding capabilities of the international sites, and that the protocol 
stopping rule for safety had not been exceeded. The protocol team’s recommendation to 


 
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proceed with enrollment at Sub-Saharan African AMC sites remains contingent upon site 
satisfaction of all regulatory and site activation requirements. 
2.4 
Correlative Studies 
Additional details and methods are provided in Appendix II, Appendix IX, and Appendix 
X. 
2.4.1 Assessment of the effect of nelfinavir on KSHV lytic gene expression in tumor 
tissue. 
As described in Section 2.1, KSHV lytic gene expression may contribute to tumor 
development and progression. We hypothesize that nelfinavir will decrease lytic 
gene expression in tumors. This will be ascertained by whole genome mRNA 
profiling at the AMC Genomics Core and immunohistochemistry (IHC) on a subset 
of viral proteins at the AMC Pathology Core Laboratory. 
2.4.2 Correlation of nelfinavir and the primary active metabolite, M8, concentrations 
with tumor response, antiviral response, and adverse effects in participants with 
KS. 
The pharmacokinetics (PK) of nelfinavir are non-linear and show considerable 
inter-patient variability. We hypothesize that higher drug levels will be associated 
with tumor response, as well as lower levels of viral lytic gene expression in tumors 
(Section 2.4.1) and KSHV copy number in saliva, PBMC, and plasma (Sections 
2.4.3 and 2.4.4). Because nelfinavir is metabolized by CYP3A and CYP2C19, 
genotyping will be performed to identify predictors of nelfinavir levels and 
response to treatment. Nelfinavir/M8 concentrations will be performed at the AMC 
Pharmacology Core Lab at Johns Hopkins University and genotyping will be 
performed at the AMC Genomics Core by targeted sequencing. 
2.4.3 Assessment of the effect of nelfinavir on KSHV copy number in saliva. 
KSHV lytic replication is common in the oropharynx15 and decreases with active 
antiviral treatment24. As such, KSHV copy number will be measured in saliva using 
quantitative polymerase chain reaction (qPCR) as a convenient estimate of antiviral 
activity. KSHV qPCR will be conducted at the AMC Genomics Core Laboratory. 
2.4.4. Exploratory: Assessment of the effect of nelfinavir on KSHV and EBV copy 
number in PBMC and plasma; and HSV, CMV, and EBV viral load in saliva. 
KSHV replication in blood may be a more relevant predictor of response to 
nelfinavir than oral replication. As such, qPCR may be used to measure KSHV in 
stored PBMC and plasma from participants. EBV viral load will also be evaluated 
in these samples. 
Additionally, HSV, CMV, and EBV viral load will be assessed in saliva at the AMC 
Virology Core. KSHV qPCR for plasma and PBMC viral load will be performed at 
the AMC Virology Core. 
PBMC/Plasma viremia: Because KSHV can reactivate sporadically, and viremia is 
not always persistent in persons with KS (present on median of 20% of days in 
endemic KS and on 67% of days in HIV-associated KS in Uganda1 the more 


 
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samples obtained, the more stability and precision in estimates. Therefore, we 
would like to obtain 2 samples pre-treatment and 8 samples on treatment. The 
timing of those samples is not important in a Poisson mixed effects model, so we 
are basing the timing on feasibility. For example, 2 samples can be achieved 
through weekly sampling during the 4 weeks pre-treatment. Eight samples on 
treatment can be obtained twice monthly in order to coordinate the blood draw 
schedule with clinical/tumor assessment visits and safety lab blood draws, which 
will also occur on this schedule (safety labs monthly but coordinated with bi-
weekly visits); this will reduce burden on participant and maximize study resources. 
Effect of the study drug on KSHV replication is an important outcome of this study. 


 
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3.0 
PARTICIPANT SELECTION 
A rostered AMC investigator (CTEP-registered physician investigator) must document that 
each protocol participant meets all stated eligibility criteria. Participating sites must have 
documentation that each eligibility requirement is satisfied prior to participant enrollment. 
In compliance with CTEP policy, no exceptions to eligibility criteria will be granted under 
any circumstance. 
NOTE: Institutions may use this section of the protocol as an eligibility checklist for source 
documentation if it has been reviewed, signed, and dated before registration/randomization 
by the study investigator. If used as source documentation, this checklist must be printed, 
the investigator must check each item to document their assessment that the participant 
meets each eligibility criterion, and the completed checklist must be maintained in the 
participant’s chart. 
Participant ID Number: 098 - ___ ___ ___ - ___ ___ ___ ___ ___ 
Patient’s Initials (F, M (optional), L): ___ ___ ___ 
3.1 
Eligibility Criteria 
__ 
3.1.1 Biopsy-proven KS involving skin (with or without visceral involvement) without 
need for urgent cytotoxic therapy. There should be no evidence of improvement in 
KS in the 4 weeks immediately prior to study enrollment and treatment. 
__ 
3.1.2 Known HIV-1 infection status, as documented by any nationally approved, licensed 
HIV rapid test performed in conjunction with screening (or enzyme-linked 
immunosorbent assay [ELISA] test kit) and confirmed by an approved test at each 
study site1. 
U.S. participants only: Alternatively, this documentation may include a record 
demonstrating that another physician has documented the participant's HIV status 
based on either: 
1. Approved diagnostic tests, or 
2. The referring physician's written record that HIV infection was documented, 
with supporting information on the participant's relevant medical history and/or 
current management of HIV infection. 
Participants enrolled outside the U.S. must have a confirmatory diagnostic test 
sequence as appropriate per national standards, detailed as above, performed 
regardless of prior documented HIV status. 
 
1 NOTE: The term “licensed” refers to a U.S. FDA-approved kit or for sites located in countries other than the United 
States, a kit that has been certified or licensed by an oversight body within that country and validated internally.  
 
WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that 
confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A 
reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a 
different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a 
plasma HIV-1 RNA viral load. 
 


 
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For HIV-negative participants, a negative result must be documented by any one of 
the nationally approved or licensed tests, including rapid tests, and must be 
performed no more than 4 weeks before enrolling to the treatment segment 
__ 
3.1.3 Participant may be either previously untreated for KS or refractory to or intolerant 
of any one or more prior KS therapies. 
__ 
3.1.4 Age ≥ 18 years. Because no dosing or adverse event data are currently available on 
the use of high dose nelfinavir in participants < 18 years of age, children are 
excluded from this study. 
__ 
3.1.5 ECOG performance status ≤ 2 (Karnofsky ≥ 50%, see Appendix III). 
__ 
3.1.6 Life expectancy of greater than 3 months as assessed by the investigator. 
__ 
3.1.7 Participants must have organ and marrow function within the following parameters 
(within 4 weeks before enrolling  for study treatment): 
• Leukocytes: ≥ 3,000/mm3 
• Absolute neutrophil count: ≥ 1,500/mm3 
• Platelets: ≥ 100,000/mm3 
• Total bilirubin: within normal limits at each study site local laboratory 
• AST (SGOT) / ALT (SGPT): ≤ 2.5 X institutional upper limit of normal (ULN) 
• Creatinine: 
o Creatinine levels ≤ upper limit of institutional normal; or 
o Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with serum 
creatinine levels above institutional normal. 
__ 
3.1.8 HIV seropositive participants must be on ART with the following criteria: 
• A complete ART regimen that adheres to the current DHHS Guidelines for the 
Use of Antiretroviral Agents in Adults and Adolescents Living with HIV 
(https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0) or any 
co-formulated combination that is FDA approved for the treatment of HIV. See 
Section 3.2.5 for details regarding eligible antiretroviral drugs. 
• The ART regimen must not include PIs (including nelfinavir); participants must 
not have received a PI-based regimen for at least 4 weeks prior to study 
enrollment. 
• Modification of ART regimen limited to eligible antiretroviral drugs while on 
study is allowable. 
• Participants must either have an undetectable HIV plasma RNA, or if plasma 
RNA detectable, it must be decreasing while on the same stable regimen for a 
minimum of 12 weeks prior to study enrollment. 
• No evidence of incomplete virologic response or virologic failure (two 
consecutive HIV RNA levels > 200 copies/mL after 24 weeks on a stable 
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study enrollment. 
__ 
3.1.9 The effects of high dose nelfinavir on the developing human fetus are unknown. 
For this reason, women of child-bearing potential must agree to use adequate 
contraception (barrier or other non-hormonal method of birth control, or 
abstinence) prior to study enrollment and for the duration of study participation. 
Hormonal contraception alone is contraindicated for pregnancy prevention in this 
study due to potential loss of efficacy from drug interactions with nelfinavir. Should 
a woman become pregnant or suspect she is pregnant while she is participating in 
this study, she should inform her treating physician immediately. 
__ 
3.1.10 Ability to understand and the willingness to sign a written informed consent 
document. 
3.2 
Exclusion Criteria 
Participants who do not fulfill the criteria as listed in Section 3.1 above, are ineligible. 
Additionally, the presence of any of the following conditions will exclude a participant 
from study enrollment: 
__ 
3.2.1 Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks 
for nitrosoureas or mitomycin-C) prior to study enrollment or those who have not 
recovered from adverse events due to agents administered more than 4 weeks prior 
to study enrollment. 
__ 
3.2.2 Participants who are receiving any other investigational agents. 
__ 
3.2.3 Participants with known brain metastases should be excluded from this clinical trial 
because of their poor prognosis and because they often develop progressive 
neurologic dysfunction that would confound the evaluation of neurologic and other 
adverse events. 
__ 
3.2.4 History of allergic reactions attributed to compounds of similar chemical or 
biologic composition to nelfinavir. 
__ 
3.2.5 Participants receiving any medications or substances that have antiviral activity 
against KSHV or that are strong inhibitors or inducers of CYP3A or 2C19 are 
ineligible. Nelfinavir (NFV) also inhibits CYP3A4 and therefore sensitive 
substrates should be avoided. Of the antiretroviral drugs, only delaviridine, 
nevirapine, cobicistat-boosted antiretrovirals (strong CYP3A4 inhibitor), 
maraviroc (sensitive CYP3A4 substrate), and protease inhibitors (strong CYP3A4 
inhibitor) are excluded. For women of child-bearing potential, hormonal 
contraception is permitted if the participant agrees to use barrier or non-hormonal 
methods of birth control or abstinence prior to enrollment and for the duration of 
the study, due to the effect of nelfinavir on contraceptive effectiveness. The 
following drugs are also prohibited: 
Strong Inhibitors of CYP3A4: 
• Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin 
• HIV: non-nucleoside reverse transcriptase inhibitors (delaviridine, nevirapine), 
protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir), 


 
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cobicistat-boosted antiretrovirals (e.g., elvitegravir). NOTE: Clinical trials 
have demonstrated that there are no clinically significant drug-drug interactions 
between nelfinavir and the following antiretrovirals: efavirenz (strong CYP3A4 
inhibitor), 
etravirine 
(strong 
CYP3A4 
inhibitor). 
Therefore, 
these 
antiretrovirals will not be excluded. 
• Antifungals: 
itraconzaole, 
ketoconazole, 
voriconazole, 
fluconazole, 
posaconazole 
• Antidepressants: nefazodone 
• Antidiuretic: conivaptan 
• GI: cimetidine, aprepitant 
• Hepatitis C: boceprevir, telaprevir 
• Miscellaneous: Seville oranges, grapefruit, or grapefruit juice and/or 
pummelos, star fruit, exotic citrus fruits, or grapefruit hybrids 
Strong Inducers of CYP3A4: 
• Glucocorticoids: cortisone (> 50 mg), hydrocortisone (> 40 mg), prednisone (> 
10 mg), methylprednisolone (> 8 mg), dexamethasone (> 1.5 mg) 
• Anticonvulsants: phenytoin, carbamazepine, primidone, phenobarbital and 
other enzyme inducing anti-convulsant drugs (EIACD) 
• Antibiotics: rifampin (rifampicin), rifabutin, rifapentine 
• Miscellaneous: St. John’s Wort, modafinil 
Strong Inhibitors of CYP2C19: 
• Antifungals: fluconazole 
Strong Inducers of CYP2C19: 
• Antibiotics: rifampin (rifampicin) 
Lists including medications and substances known or with the potential to interact 
with the CYP3A or 2C19, isoenzymes are provided in Appendix XI. 
Drugs with KSHV antiviral activity: 
• Participants receiving any medications or substances that may interfere with 
KSHV replication are ineligible. 
Because the lists of these agents are constantly changing, it is important to regularly 
consult a frequently-updated list such as 
http://medicine.iupui.edu/clinpharm/ddis. Medical reference texts such as the 
Physicians’ Desk Reference may also provide this information. Sites are 
encouraged to contact Michelle Rudek with any questions regarding eligible ART 
regimens. 
As part of the enrollment/informed consent procedures, the participant will be 
counseled on the risk of interactions with other agents, and what to do if new 


 
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medications need to be prescribed or if the participant is considering a new over-
the-counter medicine or herbal product. 
Lists including medications and substances known or with the potential to interfere 
with KSHV replication, are provided in Appendix XII. 
__ 
3.2.6 Uncontrolled intercurrent illness including, but not limited to, hepatitis C infection 
requiring treatment during the study, symptomatic congestive heart failure, 
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations 
that in the opinion of the investigator would limit compliance with study 
requirements. 
__ 
3.2.7 Pregnant women are excluded from this study because nelfinavir is a Pregnancy 
Category B agent that has not been studied at high doses in pregnant women. 
Because there is an unknown but potential risk for adverse events in nursing infants 
secondary to treatment of the mother with high dose nelfinavir, breastfeeding 
should be discontinued if the mother is treated with high dose nelfinavir. 
__ 
3.2.8 Chronic diarrhea as defined by loose or watery stools occurring more than 3 times 
daily at baseline lasting more than 4 weeks or not abating on condition-appropriate 
therapy prior to study enrollment. 
__ 
3.2.9 Participant is < 2 years free of another primary malignancy. Exceptions include 
basal cell skin cancer, Stage 0-I squamous cell cancer of the skin, cervical 
carcinoma in situ, anal carcinoma in situ. 
__ 
3.2.10 Use of systemic corticosteroid therapy (except for replacement doses of 
glucocorticoid and/or mineralocorticoid for adrenal insufficiency). Inhaled or 
intranasal corticosteroids for allergic or bronchospastic conditions are permitted. 
Physician Signature: ______________________________ Date: ___________________ 
(Optional unless this section is used as an eligibility checklist) 
3.3 
Number of Participants to be Enrolled 
3.3.1 Proposed sample size 
This study will enroll a minimum of 3 participants and a maximum of 36 
participants (planned enrollment of 18 participants with HIV infection and 18 
participants without HIV infection). 
3.3.2 Accrual rate 
Approximately 1-2 participants per month. 
3.4 
Participant Enrollment Procedures 
Sites must have this protocol approved by their Institutional Review Boards (IRB) and be 
registered for study participation with the AIDS Malignancy Consortium (AMC) 
Operations and Data Management Center (ODMC) before they may enroll participants. 
Enrollment and data collection will occur via Advantage eClinical. 
3.4.1 Registration for screening 
After an informed consent form has been signed by the participant and the protocol-


 
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specific eligibility checklist for Segment A has been completed, the participant 
must be registered for screening (AMC-098, Segment A, Screening Enrollment) 
on-line via Advantage eClinical. After successful registration into screening, the 
participant will receive an eleven-digit participant ID and will then enter the 
screening process (screening and pre-entry visits). A system generated 
confirmation email will be sent to the enroller upon successful completion of the 
participant enrollment into Segment A. If the on-line system is inaccessible, the site 
should notify the AMC ODMC (via email at amcpm@emmes.com or via phone at 
301-251-1161) for further instructions. 
3.4.2 Enrollment 
After the screening evaluations have been obtained and the participant is 
determined to be eligible, the participating site will enroll the participant into AMC-
098 Segment B (Treatment Enrollment) on-line via Advantage eClinical. 
Enrollment into Segment B should occur no more than 1 week prior to 
administration of the first dose of the protocol agent (enrollment 1 day prior to or 
on the day of treatment is strongly encouraged). 
Participants must be enrolled into AMC-098 Segment B (Treatment 
Enrollment) prior to receiving the first dose of the protocol agent. 
3.5 
Enrollment at International Sites 
Enrollment is open at all sub-Saharan Africa AMC international sites contingent upon site 
satisfaction of all regulatory and site activation requirements. 
  


 
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4.0 
TREATMENT PLAN 
4.1 
Agent Administration 
The protocol agent will be administered on an outpatient basis. A cycle is 2 weeks of 
continuous treatment (+/- 3 days according to timing of study visit/evaluations within 
window). Reported adverse events and potential risks for nelfinavir are described in 
Section 6.0. Appropriate dose modifications for nelfinavir are described in Section 5.0. No 
investigational or commercial agents or therapies other than those described below may be 
administered with the intent to treat the participant's malignancy. 
All participants will initiate protocol treatment with nelfinavir 1250 mg BID continuously 
for up to 8 weeks, and then, depending on response at the standard dose, advance to high 
dose nelfinavir at 3125 mg BID continuously (i.e., intrapatient dose escalation) for up to 
16 weeks (up to 24 weeks of treatment). 
NOTES: The participant will be requested to maintain a medication diary of each dose of 
medication (See Appendix VII). The medication diary will be returned to clinic staff at the 
end of each cycle (every two-week study visit). 
The site will be required to document study agent return by participant in source 
documents. Non-compliance with study agent administration should be noted at the time 
of diary collection and the participant should be instructed again regarding dosing 
instructions. 
Dose delays and modifications for participants experiencing toxicity are described in 
Section 5.0. Due to the known food-effects on the bioavailability of nelfinavir, clinical staff 
will provide nutritional counseling for agent administration to ensure that the participant is 
aware the drug must be consumed with a moderately-high fat meal, to increase absorption 
and decrease pharmacokinetic variability, and that acidic foods/fruit juices are avoided at 
time of administration. 
Treatment intensification will depend on the response at each treatment level: 
4.1.1 Standard dose nelfinavir (1250 mg BID) 
• Each participant must be observed for a minimum period of at least 4 weeks on 
standard dose nelfinavir before escalation to the high dose nelfinavir treatment 
level. 
• If after 4 weeks there is progressive disease (PD), the participant will advance 
to the high dose nelfinavir level. 
• If by 8 weeks there is stable disease (SD) or partial response (PR) at the standard 
dose, the participant will advance to the high dose level. 
• If there is complete response (CR) at any time at the standard dose level, 
nelfinavir will be discontinued 4 weeks after documentation of complete 
response. 
• Because dosing of study drug is continuous both during and between cycles, 
care should be taken to avoid study drug interruption. Therefore, if the study 
visit/study evaluations occur within the +/- 3 day visit window, the appropriate 


 
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amount of drug should be provided at that visit for the study interval (i.e., if the 
study visit occurs 3 days before the 14th day of the cycle, the sufficient drug 
should be provided to prevent to last 17 days, or until the date of next scheduled 
visit) 
4.1.2 High dose nelfinavir (3125 mg BID) 
• High dose nelfinavir treatment will be continued for at least 4 weeks. 
• If there is progressive disease (PD) documented after 4 weeks at the high dose 
level, nelfinavir will be discontinued. 
• If there is stable disease (SD) or partial response (PR) at the high dose level, 
high dose nelfinavir will be continued for up to 16 weeks. 
• If there is a complete response (CR), high dose treatment will be discontinued 
4 weeks after documentation of complete response. 
4.2 
General Concomitant Medication and Supportive Care Guidelines 
Because there is a potential for interaction of nelfinavir with other concomitantly 
administered drugs through the cytochrome P450 system, the case report form must capture 
the concurrent use of all other drugs, over-the-counter medications, or alternative therapies. 
A patient drug information and wallet card for potential drug-interactions will be provided 
to participants (See Appendix XIV). The site Principal Investigator should be alerted if the 
participant is taking any agent known to affect or with the potential to affect selected 
CYP450 isoenzymes. Questions regarding ART regimens may be directed to Michelle 
Rudek. Appendix XI presents guidelines for identifying medications/substances that could 
potentially interact with the study agent. 
Antiretroviral therapy is required for HIV-infected participants, with the stipulations 
detailed in Section 3.1.8. Participants may not have received a PI for at least 4 weeks prior 
to enrollment. Management of HIV will be left to the discretion of the investigator. 
Modification of antiretroviral therapy to eligible antiretroviral drugs is allowed after study 
entry and will be made at the discretion of the investigators. Any changes to antiretroviral 
therapy must be documented in the case report form (CRF). 
4.3 
Duration of Therapy 
In the absence of treatment delays due to adverse event(s), treatment may continue for a 
minimum of 8 weeks as per Section 4.1 or until one of the following criteria in Section 4.5 
applies. 
4.4 
Duration of Follow Up 
All participants will be followed for 8 weeks after removal from study or until death, 
whichever occurs first. Participants removed from study for unacceptable adverse event(s) 
(see Section 4.5) will be followed until resolution or stabilization of the adverse event(s). 
4.5 
Criteria for Removal from Treatment 
Participants will be removed from study treatment according to the criteria listed in Section 
5.0. The reason for study treatment removal and the date the participant was removed must 
be documented in the Case Report Form in Advantage eClinical. 


 
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• Disease progression after 4 weeks on high dose nelfinavir; 
• Rapid progression of disease that is deemed to be life-threatening; 
• Intercurrent illness that prevents further administration of treatment; 
• Unacceptable adverse event(s); 
• Participant decides to withdraw from the study; 
• General or specific changes in the participant's condition render the participant 
unacceptable for further treatment in the judgment of the investigator; 
• Participants who become pregnant or need to breast-feed; 
• The Investigator has the right to remove participants from the study for clinical reasons 
which he/she believes are life threatening to the participant even if such reasons do not 
fall into the toxicity classifications discussed in Section 5.0; 
• Participants requiring a cumulative delay of > 2 weeks (i.e., across cycles) or, 
participants requiring > two dose reduction (i.e., requiring reduction to < 1875 mg BID) 
throughout the duration of the study. 


 
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5.0 
DOSING DELAYS/DOSE MODIFICATIONS 
5.1 
Dose Modifications for Nelfinavir 
There will be no dosage modifications for participants receiving standard dose nelfinavir 
(1250 mg BID) as this dose is currently FDA approved for treatment of HIV infection and 
has been studied extensively in Phase I-IV studies, with clinical experience over the last 
two decades65-67. 
If at any time during administration of standard dose nelfinavir (1250 mg BID) the 
participant experiences an adverse event at a severity (grade) that requires dose 
interruptions per the tables below, study treatment will be terminated. 
Unless noted otherwise for a specific event, if at any time during administration of high 
dose nelfinavir (3125 mg BID) the participant experiences an adverse event grade that 
requires dose interruptions per the tables below, study drug will be held until the event 
resolves or improves to the specified grade, and then reduced by 625 mg BID (at 2500 mg 
BID) and continued as above unless the adverse event recurs, in which case the dose is 
reduced by another 625 mg to a minimum of 1875 mg BID if required. If the participant 
experiences an adverse event on high dose nelfinavir that does not resolve or improve to 
the specified grade after reducing the dose to 1875 mg BID, study treatment will be 
terminated. 
If any participant requires a cumulative treatment delay of > 2 weeks throughout the 
duration of the study (i.e. total across cycles), then the participant must discontinue study 
treatment. 
5.1.1 Table of Nelfinavir Dose Levels and Number of Tablets 
 
Dose Level 
Nelfinavir Dose 
Number of 625 mg Tablets 
1 (Standard Dose) 
1250 mg, BID 
2 tablets BID 
2 
1875 mg, BID 
3 tablets BID 
3 
2500 mg BID 
4 tablets BID 
4 (High Dose) 
3125 mg, BID 
5 tablets BID 
 
5.1.2 Tables of adverse events, and indications for dose modifications and management 
The AEs and corresponding severity definitions below are as classified in the NCI 
Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, as 
required in protocol Section 6.0. 


 
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Event Name 
Nausea 
Grade of Event 
Management/Next Dose for 
Standard Dose-Nelfinavir 
Management/Next Dose for 
High Dose-Nelfinavir 
≤ Grade 1 
No change in dose 
No change in dose 
Grade 2 
No change in dose 
No change in dose 
Grade 3 
Hold* until ≤ Grade 1. 
Resume at same dose level. 
Hold* until ≤ Grade 1. 
Resume at one dose level 
lower, if indicated.** 
Grade 4 
Off protocol therapy 
Off protocol therapy 
*Participants requiring a cumulative delay of > 2 weeks should go off protocol 
therapy. 
**Participants requiring > two dose reductions should go off protocol therapy. 
Recommended management: antiemetics. 
 
Event Name 
Vomiting 
Grade of Event 
Management/Next Dose for 
Standard Dose-Nelfinavir 
Management/Next Dose for 
High Dose-Nelfinavir 
≤ Grade 1 
No change in dose 
No change in dose 
Grade 2 
Hold until ≤ Grade 1. 
Resume at same dose level. 
Hold until ≤ Grade 1. 
Resume at same dose level. 
Grade 3 
Hold* until < Grade 2. 
Resume at same dose level. 
Hold* until < Grade 2. 
Resume at one dose level 
lower, if indicated.** 
Grade 4 
Off protocol therapy 
Off protocol therapy 
*Participants requiring a cumulative delay of > 2 weeks shall go off protocol 
therapy. 
**Participants requiring > two dose reductions shall go off protocol therapy. 
Recommended management: antiemetics. 
 


 
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Event Name 
Diarrhea 
Grade of Event 
Management/Next Dose 
for Standard Dose-
Nelfinavir 
Management/Next Dose for 
High Dose-Nelfinavir 
≤ Grade 1 
No change in dose 
No change in dose 
Grade 2 
considered 
tolerable or 
easily managed 
Add supportive care as 
indicated. No change in 
dose. 
Add supportive care as 
indicated. No change in dose. 
Grade 2 
considered 
intolerable to 
participant or 
deemed 
unacceptable in 
the investigator’s 
judgment 
Hold until ≤ Grade 1. 
Resume at same dose level. 
Hold until ≤ Grade 1. 
Resume at same dose level. 
Grade 3 
Hold* until ≤ Grade 2 if 
tolerable, or ≤ Grade 1 if 
considered intolerable at 
Grade 2. Resume at same 
dose level. 
Hold* until ≤ Grade 2 if 
tolerable, or ≤ Grade 1 if 
considered intolerable at 
Grade 2. Resume at one dose 
level lower, if indicated.** 
Grade 4 
Off protocol therapy 
Off protocol therapy 
*Participants requiring a cumulative delay of >2 weeks shall go off protocol 
therapy. 
**Participants requiring > two dose reductions shall go off protocol therapy. 
Recommended management: loperamide antidiarrheal therapy. 
Dosage schedule: 4 mg at first onset, followed by 2 mg with each loose motion 
until diarrhea-free for 12 hours (maximum dosage: 16 mg/24 
hours). 
Adjunct anti-diarrheal therapy is permitted and shall be recorded when used. 
 
Event Name 
Neutropenia 
Grade of Event 
Management/Next Dose for 
Standard Dose-Nelfinavir 
Management/Next Dose for 
High Dose-Nelfinavir 
≤ Grade 1 
No change in dose 
No change in dose 
Grade 2 
No change in dose 
No change in dose 


 
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Event Name 
Neutropenia 
Grade of Event 
Management/Next Dose for 
Standard Dose-Nelfinavir 
Management/Next Dose for 
High Dose-Nelfinavir 
Grade 3 
Hold* until < Grade 2. 
Resume at same dose level. 
Hold* until < Grade 2. 
Resume at one dose level 
lower, if indicated.** 
Grade 4 
Off protocol therapy 
Off protocol therapy 
*Participants requiring a cumulative delay of > 2 weeks shall go off protocol 
therapy. 
**Participants requiring > two dose reductions shall go off protocol therapy. 
 
Event Name 
Thrombocytopenia 
Grade of Event 
Management/Next Dose for 
Standard Dose-Nelfinavir 
Management/Next Dose for 
High Dose-Nelfinavir 
≤ Grade 1 
No change in dose 
No change in dose 
Grade 2 
Hold until ≤ Grade 1. 
Resume at same dose level. 
Hold until ≤ Grade 1. 
Resume at same dose level. 
Grade 3 
Hold* until ≤ Grade 1. 
Resume at same dose level. 
Hold* until ≤ Grade 1. 
Resume at one dose level 
lower, if indicated.** 
Grade 4 
Off protocol therapy 
Off protocol therapy 
*Participants requiring a cumulative delay of > 2 weeks shall go off protocol 
therapy. 
**Participants requiring > two dose reductions shall go off protocol therapy. 


 
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6.0 
ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. The 
following list of AEs (Section 6.1) and the characteristics of an observed AE (Section 6.2) 
will determine whether the event requires expedited reporting via the CTEP Adverse Event 
Reporting System (via CTEP-AERS) in addition to routine reporting. 
CTEP-registered physician investigators and CTEP-registered advanced practice clinicians 
who are non-physician investigators (i.e.,, NP or PA) may perform toxicity assessment per 
local licensure requirements. 
The CTEP Version 5.0 of the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) will be utilized for AE reporting. The CTEP Version 5.0 of the CTCAE is 
identified and located on the CTEP website at 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
All appropriate treatment areas should have access to a copy of the CTEP Version 5.0 of 
CTCAE. 
This study will be monitored by the Clinical Data Update System (CDUS). Cumulative 
CDUS data will be submitted quarterly to CTEP by electronic means. Reports are due 
January 31, April 30, July 31, and October 31. 
6.1 
Comprehensive Adverse Events and Potential Risks Lists 
6.1.1 Adverse event list for nelfinavir 
Agent not supplied by CTEP: Refer to Section 7.0 or the Viracept® package 
insert(s) for the comprehensive list of adverse events. 
Listed below are adverse events occurring in > 2% of participants receiving 
standard dose nelfinavir (Viracept®). 
• Diarrhea 
• Nausea 
• Flatulence 
• Rash 
With high dose nelfinavir, neutropenia has been observed. 
6.2 
Classification of AEs by Severity and Relationship to Study Drug Administration 
6.2.1 Adverse Event: Any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a 
medical treatment or procedure regardless of whether it is considered related to the 
medical treatment or procedure (attribution of unrelated, unlikely, possible, 
probable, or definite). 
6.2.2 Life-threatening Adverse Event: Any AE that places the participant or participant, 
in view of the Investigator, at immediate risk of death from the reaction. 
6.2.3 Serious Adverse Event (SAE): Any AE occurring at any dose that results in any of 
the following outcomes: Death, a life-threatening AE, inpatient hospitalization or 


 
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prolongation of existing hospitalization, a persistent or significant disability/ 
incapacity, or a congenital anomaly/birth defect. 
6.2.4 Please note for hospitalization – All hospitalizations (or prolongation of existing 
hospitalization) for medical events equivalent to CTCAE Grade 3, 4, 5 must be 
reported regardless of the requirements for Phase of study, expected or unexpected, 
and attribution. For example, do not report an admission for pharmacokinetic 
sampling, but do report an admission for a myocardial infarction.  
6.2.5 Toxicity: Toxicity is a term NOT clearly defined by regulatory organizations. 
Toxicity has been described as an AE that has an attribution of possibly, probably 
or definitely related to investigational treatment. To minimize confusion the NCI 
would recommend that the term toxicity NOT be utilized for AE reporting 
purposes. The CTCAE continues to use the term ‘toxicity’ because of familiarity. 
6.2.6 Unexpected Adverse Event: Any AE that is not listed in available sources including 
the package insert, the Investigator’s Brochure, or the protocol. 
6.2.7 CTEP Adverse Event Reporting System (CTEP-AERS): An electronic system for 
expedited submission of AE reports. 
6.2.8 Attribution: The determination of whether an AE is related to a medical treatment 
or procedure. Attribution categories: 
Definite – The AE is clearly related to the investigational agent. 
Probable – The AE is likely related to the investigational agent. 
Possible – The AE may be related to the investigational agent. 
Unlikely – The AE is doubtfully related to the investigational agent. 
Unrelated – The AE is clearly NOT related to the investigational agent. 
6.3 
Expedited Adverse Event Reporting 
6.3.1 Expedited AE reporting for this study must use CTEP-AERS (CTEP Adverse Event 
Reporting System), accessed via the CTEP home page (http://ctep.cancer.gov). The 
reporting procedures to be followed are presented in the “CTEP, NCI Guidelines: 
Adverse Event Reporting Requirements” which can be downloaded from the CTEP 
home page (http://ctep.cancer.gov). These requirements are briefly outlined in the 
table below (Section 6.3.3). 
A 24-hour notification is to be made to AMC ODMC by telephone at 301-251-
1161, only when Internet connectivity is disrupted. Once Internet connectivity is 
restored, a 24-hour notification phoned in must be entered electronically into 
CTEP-AERS by the original submitter at the site. 
6.3.2 CTEP-AERS is programmed for automatic electronic distribution of reports to the 
following individuals: Study Coordinator of the Lead Organization, Principal 
Investigator, and the local treating physician. CTEP-AERS provides a copy feature 
for other e-mail recipients.  
6.3.3 Expedited reporting guidelines 
Use the NCI protocol number and the protocol-specific participant ID assigned 
during trial registration on all reports. 


 
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Note: A death on study requires both routine and expedited reporting regardless of 
causality, unless as noted below. Attribution to treatment or other cause must be 
provided. 
Death due to progressive disease should be reported as Grade 5 “General 
disorders and administration site conditions – Disease Progression.” Evidence 
that the death was a manifestation of underlying disease (e.g., radiological changes 
suggesting tumor growth or progression: clinical deterioration associated with a 
disease process) should be submitted.  
Expedited Reporting Requirements for Adverse Events that Occur in a Non-IND/IDE trial 
within 30 Days of the Last Administration of a Commercial Agent 1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE: Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or 
not they are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
• 
A congenital anomaly/birth defect. 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization may be 
considered serious when, based upon medical judgment, they may jeopardize the participant or participant and may 
require medical or surgical intervention to prevent one of the outcomes listed in this definition. (FDA, 21 CFR 
312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via CTEP-
AERS within the timeframes detailed in the table below. 
Hospitalization 
Grade 1  
timeframes 
Grade 2  
Timeframes 
Grade 3  
Timeframes 
Grade 4 & 5  
Timeframes 
Resulting in Hospitalization 
≥ 24 hrs. 
10 Calendar Days 
24-Hour 5 
Calendar Days 
Not resulting in 
Hospitalization ≥ 24 hrs. 
Not required 
10 Calendar Days 
Expedited AE reporting timelines are defined as: 
● 
“24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-AERS within 24 hours of learning 
of the AE, followed by a complete expedited report within 5 calendar days of the initial 24-hour report. 
● 
“10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 calendar days of 
learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows: 
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
All Grade 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization 
Grade 3 adverse events 
2 For studies using PET or SPECT agents, the AE reporting period is limited to 10 radioactive half-lives, rounded 


 
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UP to the nearest whole day, after the agent/intervention was last administered. Footnote “1” above applies after 
this reporting period. 
Effective Date: May 5, 2011 
6.3.4 Additional protocol-specific expedited adverse event reporting exclusions 
For this protocol only, the AEs/grades listed below do not require expedited 
reporting via CTEP-AERS. However, they still must be reported through the 
routine reporting mechanism (Section 6.4): 
 
CTCAE SOC 
Adverse Event 
Grade 
Hospitalization/ Prolongation 
of Hospitalization 
Gastrointestinal Disorders 
Nausea 
≤ 2 
Prolongation of Hospitalization 
Gastrointestinal Disorders 
Diarrhea 
≤ 2 
Prolongation of Hospitalization 
Gastrointestinal Disorders 
Vomiting 
≤ 2 
Prolongation of Hospitalization 
*AEs considered with an attribution to NFV of possible or greater 
6.3.5 For Uganda Cancer Institute Only: SAE reporting to the Ugandan National Drug 
Authority 
Once the trial is opened in Uganda, this protocol will also comply with the National 
Drug Authority’s requirements for safety reporting. 
The requirement for the investigator to notify the sponsor of any serious adverse 
event that occurs in a participant during a clinical trial will occur via Adverse Event 
form in Advantage eClinical (see Section 6.4), which will include any suspected 
unexpected serious adverse reactions. 
The sponsor shall, within seven days of becoming aware, report to the Authority 
and the Uganda National Council of Science and Technology or an institution 
authorized to receive the report by the Uganda National Council of Science and 
Technology, any suspected unexpected serious adverse reactions. 
Where urgent safety measures are taken to protect the participants against any 
immediate hazard to the health or safety of trial participants due to participation in 
this investigation, the sponsor shall within three working days from the date the 
safety measures are taken, give written notice to the Authority of the measures 
taken and the circumstances that give rise to the measures. 
6.3.6 SAE reporting to Pfizer Inc. 
The following incidents will be reported to Pfizer Inc. within 24 hours of the AMC 
ODMC’s awareness, in accordance with the agent supply agreement: 
• All deaths 
• Non-fatal SAEs in reporting period assessed as related to nelfinavir and 
unexpected 
• Related SAEs that occur after the reporting period 


 
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• Exposure during pregnancy or lactation, occupational exposure, or lack of 
effect 
As the manufacturer of the agent, Pfizer will be responsible for reporting any 
serious and unexpected suspected adverse drug reactions (SUSAR) to the FDA in 
accordance with 21 CFR 314.80. 
6.4 
Routine Adverse Event Reporting 
All adverse events must be reported in routine study data submissions. AEs reported 
through CTEP-AERS must also be reported in routine study data submissions. All SAEs 
must be entered in an Adverse Event form within 24 hours of the investigator’s awareness. 
In assessing laboratory results, an abnormal laboratory value will be considered clinically 
significant if it is characterized by one or more of the following criteria: 
1. Is judged by the investigator to have a causal relationship to the investigational agent 
2. Requires clinical intervention or monitoring, such as: close observation, more frequent 
follow-up assessments, further diagnostic intervention, treatment/therapeutic 
intervention, or protocol therapy dose modification 
3. Is associated with clinical signs or symptoms, which may suggest a disease and/or 
organ toxicity, or may represent a new condition or worsening of a baseline condition 
4. Is associated with a serious adverse event, or is otherwise judged by the Investigator to 
be of significant clinical impact 
Laboratory results that are proven erroneous by repeat testing will not be considered 
clinically significant. 
In general, a laboratory abnormality that is not clinically significant will be consistent with 
CTCAE grade 1 (mild) or 2 (moderate) severity, as categorized by the relevant severity 
description in the Investigations System Organ Class (SOC) or Metabolism and Nutrition 
Disorders SOC. Investigators may not designate laboratory abnormalities that are 
consistent with grade 3 or greater severity as not clinically significant. 
All laboratory values deemed clinically significant will be subsequently reported as AEs 
unless the result is a sign of a clinical diagnosis that is reported as an AE. For example, 
clinically relevant laboratory results for electrolyte abnormalities would not require 
separate reporting as AEs if they are signs of a clinical diagnosis and reported AE for 
dehydration. 
6.5 
Secondary Malignancy 
Not relevant for nelfinavir. 
6.6 
Second Malignancy 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is NOT 
a metastasis from the initial malignancy). Second malignancies require ONLY routine 
adverse event reporting. 


 
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7.0 
PHARMACEUTICAL INFORMATION 
A list of the adverse events and potential risks associated with the investigational or 
commercial agents administered in this study can be found in Section 6.1. 
7.1 
Nelfinavir (Viracept®, nelfinavir mesylate) 
[NOTE: Please refer to the commercial package insert for more information.] 
7.1.1 Other Names: Viracept®; 159989-64-7; VRX496; UNII-HO3OGH5D7. 
The chemical name for nelfinavir mesylate is 
[3S-[2(2S*, 3S*), 3α, 4aβ, 8aβ]]-N-(1, 1-dimethylethyl)decahydro-2-[2-hydroxy-3-
[(3-hydroxy2-methylbenzoyl)amino]-4-(phenylthio)butyl]-3-isoquinoline 
carboxamide monomethanesulfonate (salt) and the molecular weight is 663.90 
(567.79 as the free base). 
 
7.1.2 Classification: human immunodeficiency virus (HIV-1) protease inhibitor. 
7.1.3 Mode of action 
Nelfinavir is an inhibitor of the HIV-1 protease. Inhibition of the viral protease 
prevents cleavage of the gag and gag-pol polyprotein resulting in the production 
of immature, non-infectious virus. Nelfinavir also has activity against a number of 
tumor types and herpesvirus replication in vitro (see Section 2.2.1). 
7.1.4 Ingredients 
Nelfinavir tablets are available for oral administration as a white oval tablet with a 
clear film coating in 625 mg strength (as nelfinavir free base). 
Each tablet contains the following common inactive ingredients: calcium silicate, 
crospovidone, magnesium stearate, hypromellose, and triacetin. In addition, the 625 
mg tablet contains colloidal silicon dioxide. 
7.1.5 Storage and stability 
Nelfinavir tablets and should be stored at 15° to 30°C (59° to 86°F) away from 
sources of heat and moisture. Keep container tightly closed. 


 
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7.1.6 Dose specifics and administration 
Nelfinavir should be taken with a meal. Participants unable to swallow the 625 mg 
tablets should dissolve the tablets in a small amount of water. Once dissolved, 
participants should mix the cloudy liquid well, and consume it immediately. The 
glass should be rinsed with water and the rinse swallowed to ensure the entire dose 
is consumed. 
7.1.7 Preparation: 625 mg tablets. 
7.1.8 Route of administration: Oral 
7.1.9 Incompatibilities: Not applicable (oral). 
7.1.10 Availability: VIRACEPT® (nelfinavir mesylate) 625 mg: White oval tablet with a 
clear film coating engraved with "V" on one side and "625" on the other. Bottles of 
120 (625 mg) tablets – NDC 63010-027-70 VIRACEPT® (nelfinavir mesylate). 
7.1.11  Side Effects: Most common adverse reactions (≥ 2%) of moderate or severe 
intensity in adults and adolescents (13 years and older) are diarrhea, nausea, rash, 
and flatulence. 
Adverse events occurring in less than 2% of participants receiving VIRACEPT® in 
all phase II and III clinical trials and considered at least possibly related or of 
unknown relationship to treatment and of at least moderate severity are listed 
below. 
Body as a Whole: abdominal pain, accidental injury, allergic reaction, asthenia, 
back pain, fever, headache, malaise, pain, and redistribution/accumulation of body 
fat. 
Digestive System: anorexia, dyspepsia, epigastric pain, gastrointestinal bleeding, 
hepatitis, mouth ulceration, pancreatitis, and vomiting. 
Hemic/Lymphatic System: anemia, leukopenia, and thrombocytopenia. 
Metabolic/Nutritional System: increases in alkaline phosphatase, amylase, creatine 
phosphokinase, lactic dehydrogenase, SGOT, SGPT, and gamma-glutamyl 
transpeptidase; hyperlipemia, hyperuricemia, hyperglycemia, hypoglycemia, 
dehydration, and liver function tests abnormal. 
Musculoskeletal System: arthralgia, arthritis, cramps, myalgia, myasthenia, and 
myopathy. 
Nervous System: anxiety, depression, dizziness, emotional lability, hyperkinesia, 
insomnia, migraine, paresthesia, seizures, sleep disorder, somnolence, and suicide 
ideation. 
Respiratory System: dyspnea, pharyngitis, rhinitis, and sinusitis. 
Skin/Appendages: dermatitis, folliculitis, fungal dermatitis, maculopapular rash, 
pruritus, sweating, and urticaria. 
Special Senses: acute iritis and eye disorder. 
Urogenital System: kidney calculus, sexual dysfunction, and urine abnormality. 


 
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The following adverse reactions have been identified during post-approval use of 
VIRACEPT®. Because these reactions are reported voluntarily from a population 
of uncertain size, it is not always possible to reliably estimate their frequency or 
establish a causal relationship to drug exposure. 
Body as a Whole: hypersensitivity reactions (including bronchospasm, moderate to 
severe rash, fever, and edema). 
Cardiovascular System: QTc prolongation, torsades de pointes. 
Digestive System: jaundice. 
Metabolic/Nutritional System: bilirubinemia, metabolic acidosis. 
7.1.12 Nursing Implications: Women receiving high dose nelfinavir should not breastfeed. 
7.1.13 References: PubChem: Open Chemistry Database; VIRACEPT® Highlights of 
Prescribing Information (ViiV Healthcare Company, updated 05/2013) 
7.2 
Drug Orders, Transfers, Returns, and Accountability 
Nelfinavir mesylate is being supplied by Pfizer, Inc. for this trial. Locally-sourced supplies 
of a FDA-approved Viracept (nelfinavir mesylate) 625 mg tablets may be sourced by the 
clinical site and reimbursed by the AMC with prior approval from the AMC Operations 
and Data Management Center. The principal investigator (or his/her authorized designee) 
at each study site will request study agent from the AMC’s vendor for study agent 
distribution. International sites must consult the Manual of Procedures for drug ordering 
instructions. Information and forms for ordering study agent will be maintained in the 
password-protected section of the AMC Operations website for protocol AMC-098 
(www.AIDSCancer.org). 
Medication should be kept in a secured locked area at the study site in accordance with 
applicable regulatory requirements. Participants should be instructed to keep medication in 
its original container and stored at room temperature (15-30°C), away from heat and 
moisture. The site is responsible for the destruction of study agent returned by study 
participants according to local procedures. 
The Investigator, or a responsible party designated by the Investigator, must maintain a 
careful record of the inventory and disposition of all drugs received using the NCI Drug 
Accountability Record Form (Oral DARF) (available on the CTEP home page 
(http://ctep.cancer.gov) or contacting the Pharmaceutical Management Branch by email at 
pmbafterhours@mail.nih.gov). The DARFs document the drug delivery date to the site, 
inventory at the site, use by each study participant, and disposal of the drug (if applicable). 
A site-specific accountability record, either manual or electronic, may be used if it includes 
all the information required on the NCI Investigational Drug Accountability Record and if 
the paper printout is identical to the NCI accountability record. Institutional pharmacists 
must only supply participants enough study drug to last until their subsequent study visit 
(i.e., no extra study drug should be given. The pharmacist must dispense nelfinavir in the 
original container. The nelfinavir removed from the bottle prior to dispensing should be 
destroyed according to local policy. Pharmacists must log the number of capsules being 
dispensed on the first line of the oral DARF. On the next line, record the number of capsules 
wasted and connect the two lines with a bracket (either ‘{‘ or ‘[’) outside of the table on 


 
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the left side.  
 
 


 
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8.0 
CLINICAL AND LABORATORY EVALUATIONS 
Schedules shown in the Study Calendar below are provided in Appendix I. 
8.1 
Screening/Baseline Evaluations 
Baseline evaluations (including scans and x-rays) are to be conducted within 4 weeks prior 
to study enrollment into Segment B (Treatment Enrollment), unless otherwise specified 
below. 
8.1.1 Recording of demographics, medical history, history of Centers for Disease Control 
and Prevention (CDC) HIV risk group and AIDS defining illnesses, physical 
examination (including vital signs, height, and weight), nutrition assessment, 
ECOG or KPS score, assessment of KS sign and symptoms, and medication review. 
8.1.2 Diagnostic KS biopsy if not previously done at any time (can be the same biopsy 
collected for immunohistochemistry correlative studies). Any biopsy report is 
sufficient for the domestic sites; participants at the international sites require 
diagnosis by the AMC-approved pathologist identified for that site. 
8.1.3 Tumor assessments with photographic record must be performed prior to initiating 
treatment. These may be performed on Day 0, but no earlier than 7 days before 
initiating study treatment. Tumor assessments and photographs should be 
performed as outlined in the Kaposi’s Sarcoma (KS) Tumor Assessment Manual of 
Procedures (MOP). 
8.1.4 Staging criteria (to be done within 4 weeks prior to study enrollment): KS staging 
will be based on the modified AIDS Clinical Trials Group (ACTG) Oncology 
Committee Staging Criteria as outlined in the KS Tumor Assessment MOP. 
8.1.5 HIV serology if negative or not previously done. 
8.1.6 HIV plasma viral load, and CD4 count and percentage if HIV-positive. 
8.1.7 Chest X-ray. 
8.1.8 Pregnancy testing by beta-HCG if female of childbearing age. Repeat pregnancy 
testing required immediately prior to starting standard dose nelfinavir (on Day 0) if 
previously performed within the 4 weeks before Day 0. 
8.1.9 Electrocardiogram (EKG). 
8.1.10 Complete blood count (CBC) with differential and chemistries must be performed 
within 4 weeks before starting treatment. Chemistries include calcium, sodium, 
potassium, carbon dioxide (CO2), chloride, AST (SGOT)/ALT( SGPT), BUN, 
creatinine, direct and total bilirubin, fasting glucose, and triglycerides. 
8.1.11 Optional donation to the AIDS and Cancer Specimen Resource (ACSR). (See 
Appendix V for ACSR Informed Consent Form and Appendix IV for ACSR 
Specimen Preparation and Shipping Instructions) (for U.S. participants only). 
8.1.12 Correlative Studies (see Section 2.4, Appendix II, Appendix IX, and Appendix X) 
8.1.12.1 Oral swabs for KSHV, HSV, EBV, and CMV qPCR collected on 14 
separate days pre-treatment (14 samples total) between weeks -4 and 0. 
Sample collection will be performed between study visits and will be self-


 
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collected by the participant and returned at the visit to the study clinician. 
See Appendix XIII for participant instructions for the oral swab 
collection. Training and any re-training provided to the participant must 
be documented in the participant’s study record. 
8.1.12.2 Baseline biopsies: two biopsy specimens will be obtained prior to 
initiating nelfinavir: one 3 mm KS biopsy for immunohistochemistry 
(collected in formalin) AND one 3 mm for viral gene expression arrays 
(collected in RNAlater). For IHC, the same biopsy may be used for those 
participants that require a diagnostic KS biopsy for study entry (see 
Section 8.1.2). If biopsy specimens for ICH studies are deemed unusable 
or are inadequate to perform IHC studies, 6 additional slides from the 
diagnostic biopsy may be collected for analysis. 
8.1.12.3 Blood (8.5 mL in a yellow top ACD tube) sample collected once per week 
during pre-treatment for a total of 2 samples for KSHV and EBV qPCR 
of PBMC and plasma. PBMC DNA from this sample will also be used for 
genotyping of CYP3A/CYP2C19 will be performed to assess 
nelfinavir/M8 metabolism/pharmacogenomics. 
The timing of these samples is based on feasibility. For example, 2 
samples can be achieved through weekly sampling in the 4 weeks pre-
treatment. 
8.1.13 Provide study drug, nutritional counseling, Participant Drug Information Handout 
and Wallet Card (Appendix XIV), Participant Instructions for Oral Swabs 
(Appendix XIII), and Participant Drug Diary (see Appendix VII). Nutritional 
counseling is required to ensure that participants are consuming nelfinavir with the 
appropriate foods. The site must query the participant regarding this information 
(open-ended questions are recommended) and capture the response in the source. 
The AMC-098 Documentation of Nutrition Assessment and Counseling source 
document provided on the AMC member’s only website or an equivalent document 
may be used for this purpose. 
8.2 
Evaluations during Treatment 
Efforts should be made to keep participants on the proper study visit schedule. Each study 
visit while on treatment may be conducted +/- 3 days from the evaluation schedule. 
8.2.1 Medical history, physical exam (including vital signs and weight), medication 
review (adherence review), nutrition assessment, and assessment of KS sign and 
symptoms. 
8.2.2 KS tumor response assessment with photographic documentation to be completed 
each visit, every 2 weeks as outlined in the KS Tumor Assessment MOP. Response 
of KS to treatment is described in Section 9.0. 
A chest X-ray should be performed to evaluate tumor response only for participants 
with pulmonary KS or new pulmonary symptoms. 
8.2.3 Pregnancy testing by beta-HCG if female of childbearing age immediately prior to 
starting high-dose nelfinavir. 


 
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8.2.4 HIV plasma viral load if HIV-positive every 8 weeks while on nelfinavir. 
8.2.5 Complete blood count with differential and chemistries described in Section 8.1.10 
every 4 weeks while on high dose nelfinavir. 
8.2.6 Fasting glucose and triglycerides every 8 weeks while on high dose nelfinavir. 
8.2.7 EKG 2 weeks after starting standard dose nelfinavir, and 2 weeks after starting high 
dose nelfinavir. 
8.2.8 Correlative Studies (see Section 2.4, Appendix II, Appendix IX, and Appendix X) 
8.2.8.1 Oral swabs for KSHV, HSV, EBV, and CMV, qPCR collected twice weekly 
for 7 weeks (14 samples) starting one week after initiation of high dose 
nelfinavir treatment. Sample collection between study visits will be self-
collected by the participant. See Appendix XIII for participant instructions 
for the oral swab collection. 
8.2.8.2 On-treatment biopsies 
• Two weeks after initiating standard dose nelfinavir, two 3 mm KS 
biopsies will be obtained: one for immunohistochemistry (collected in 
formalin) AND one for viral gene expression arrays (collected in 
RNAlater). 
• Two weeks after initiating high dose nelfinavir, two 3 mm KS biopsies 
will be obtained: one for immunohistochemistry (collected in formalin) 
AND one for viral gene expression arrays (collected in RNAlater). 
8.2.8.3 Blood (6 mL in a lavender top EDTA tube) for assessment of nelfinavir/M8 
concentrations (pharmacokinetics), prior to dosing at each study visit (every 
2 weeks) while on treatment, starting on Week 1/cycle 1 through the 
completion of Week 15/cycle 9 (a total of 9 samples will be collected) A -3 
day window is permitted. 
8.2.8.4 Blood (8.5 mL in a yellow top ACD tube) sample collected at each clinic 
visit (every 2 weeks) while on high dose nelfinavir for KSHV and EBV 
qPCR of PBMC and plasma. 
The timing of these samples is basing the timing on feasibility. The eight 
samples on treatment can be obtained twice monthly in order to coordinate 
the blood draw schedule with clinical/tumor assessment visits and safety lab 
blood draws, which will also occur on this schedule (safety labs monthly 
but coordinated with bi-weekly visits); this will reduce burden on 
participant and maximize study resources. 
8.2.9 Provide study drug, nutritional counseling, Participant Instructions for Oral Swabs 
(one week after initiation of high dose nelfinavir, Appendix XIII), and Participant 
Drug Diary (see Appendix VII). Sufficient drug to provide continuous dosing 
between cycles/study visits should be provided as long as visits lie within the visit 
window. 
8.3 
Early Treatment Discontinuation Evaluations 


 
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8.3.1 Participants who discontinue protocol treatment for adverse events as outlined in 
Section 5.0 should have the following evaluations and laboratory tests within 7 days 
after discontinuation of nelfinavir: 
8.3.1.1 Medical history, physical exam (including vital signs and weight), 
medication review (adherence review), nutrition assessment. 
8.3.1.2 KS tumor assessment with photographic documentation as outlined in the 
KS Tumor Assessment MOP. Response of KS to treatment is described in 
Section 9.0. 
A chest X-ray should be performed to evaluate tumor response only for 
participants with pulmonary KS or new pulmonary symptoms. 
8.3.1.3 Complete blood count with differential, and chemistries as described in 
Section 8.1.10. 
8.3.1.4 Fasting glucose and triglycerides. 
8.3.1.5 HIV plasma viral load and CD4 count if HIV-positive. 
8.4 
Follow-up Evaluations 
8.4.1 All participants will have the following evaluations and laboratory tests 8 weeks (± 
7 days) after discontinuation of nelfinavir. Follow-up evaluations must occur before 
beginning alternative therapy. If in the opinion of the treating investigator the 
participant needs to begin alternative therapy prior to follow up, then the follow up 
visit may occur earlier than 8 weeks (± 7 days) after discontinuation of nelfinavir. 
8.4.1.1 Medical history, physical exam (including vital signs and weight). 
8.4.1.2 KS tumor assessment with photographic documentation as outlined in the 
KS Tumor Assessment MOP. Response of KS to treatment is described in 
Section 9.0. 
A chest X-ray should be performed to evaluate tumor response only for 
participants with pulmonary KS or new pulmonary symptoms. 
8.4.1.3 Complete blood count with differential, and chemistries as described in 
Section 8.1.10. 
8.4.1.4 Fasting glucose and triglycerides. 
8.4.1.5 HIV plasma viral load and CD4 count if HIV-positive. 
8.5 
Final Evaluations, Off Study 
At the completion of all follow-up evaluations described in Section 8.4, the Off-Study 
Summary Form should be completed in Advantage eClinical. 
8.5.1 Participants completing study per-protocol. 
8.5.2 Participants who discontinue the study early. 


 
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9.0 
MEASUREMENT OF EFFECT 
For the purposes of this study, participants should be re-evaluated for response every 2 
weeks. See Appendix I for the KS Tumor Assessment schedule. 
CTEP-registered physician investigators and CTEP-registered advanced practice clinicians 
who are non-physician investigators (i.e., NP or PA) may perform toxicity and response 
assessment per local licensure requirements. 
Evaluable for Toxicity: All participants will be evaluable for toxicity from the time of their 
first treatment with nelfinavir. 
Evaluable for Objective Response: Only those participants who have measurable disease 
present at baseline and have received study drug will be considered evaluable for response. 
Response status will be classified as complete response (CR), partial response (PR), stable 
disease (SD), or progressive disease (PD). 
9.1 
Definition of Response 
Response and progression will be evaluated in this study using the AIDS Clinical Trials 
Groups (ACTG) response criteria for Kaposi sarcoma. 
9.1.1 Complete response: Complete response (CR) is defined as the absence of any 
detectable residual disease, including tumor-associated edema, persisting for at 
least 4 weeks. In participants with pigmented (brown or tan) macular skin lesions 
persist after apparent complete response, biopsy of at least one representative lesion 
is required in order to document the absence of malignant cells. In participants 
known to have had visceral disease, an assessment at restaging with appropriate 
endoscopic or radiographic procedures should be made. 
9.1.2 Partial response (PR) is defined as no new lesions (skin or oral), or new visceral 
sites of involvement (or the appearance or worsening of tumor-associated edema or 
effusions); AND 
• A 50% or greater decrease in the number of all previously existing lesions 
lasting for at least 4 weeks; OR 
• Complete flattening of at least 50% of all previously raised lesions (i.e., 50% of 
all previously nodular or plaque-like lesion become macules); OR 
• A 50% decrease in the sum of the products of the largest perpendicular 
diameters of the marker lesions. 
Note: Participants with residual tumor-associated edema or effusion who otherwise 
meet the criteria for complete response will be classified as having a partial 
response. 
9.1.3 Stable disease is defined as any response not meeting the criteria for CR, PR, or 
progressive disease. 
9.1.4 Progressive disease (PD) is defined as follows: 
For participants with ≤ 50 cutaneous lesions 
• 25% increase in the sum of perpendicular diameters of the indicator lesions, OR 


 
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• ≥ 25% increase in the total lesion count, or a minimum of 5 new lesions, 
whichever is greater, OR 
• ≥ 25% increase in the number of raised lesions (minimum of 5 new raised 
lesions if there are very few raised lesions, for example ≤ 8), whichever is 
greater. 
Note: There are body sites where disease is particularly difficult to evaluate, and a 
few new lesions may be counted in spite of the fact that a participant is not actually 
progressing. For example, lesions of the foot, particularly those which are flat, are 
difficult to evaluate because their intensity may be variable based on how much 
edema is present, how much the person walked the day before, how long their feet 
have been in a dependent position prior to the physical exam, etc. 
For participants with > 50 cutaneous lesions 
• ≥ 25% increase in the sum of the perpendicular diameters of the indicator 
lesions, OR 
• ≥ 25% increase in the total number of lesions in the prospectively defined 
anatomic sites containing representative numbers of lesions, OR 
• A total of 5 new lesions in anatomic sites which were previously documented 
as having no evidence of cutaneous disease on the whole body diagram, OR  
• ≥ 25% increase in the number of raised lesions (minimum of 5 raised lesions if 
there are very few raised lesions, for example < 8) whichever is greater. 
Photographic documentation of “gross” or significant progression, particularly 
in areas that were not being followed, will be of particular value. 
In order to classify a response as PR, the participant must have at least a PR in 
either the cutaneous or noncutaneous sites of disease, and no evidence of 
progression as defined in the above criteria. In order to classify a response as a CR, 
the participant must have a CR in both the cutaneous (if applicable) and 
noncutaneous (if applicable) sites of disease, and no evidence of progression as 
defined by the above criteria. 
9.1.5 Noncutaneous progression 
Progressive disease includes new visceral sites of involvement or progression of 
visceral disease or the development of new or increasing tumor-associated edema 
or effusion lasting at least 1 week, which interferes with the participant’s normal 
activities. Progressive visceral disease, for measurable and evaluable disease, 
should be analogous to non-KS response criteria. 
9.1.6 Recurrent disease  
Recurrent disease is defined as the appearance of tumor following documentation 
of a complete remission. 
9.1.7 Time to response 
Time to response is defined as time from the first dose of chemotherapy until 


 
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documentation of first response. 
9.1.8 Time to progression 
Time to progression is defined as time from initiation of chemotherapy to 
documentation of first progression. 
9.1.9 Response duration 
Response duration is defined as the time from first documentation of response to 
documentation of first progression. 


 
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10.0 
STATISTICAL CONSIDERATIONS 
10.1 
Study Design/Endpoints 
Currently approved cytotoxic chemotherapy regimens result in a roughly 40% partial or 
complete response (total response) rate in persons who are not ART-naïve (who initiate 
ART and chemotherapy concurrently). Our hypothesis is that the dose-escalation regimen 
will result in at least a 20% improvement in PR or CR above the historically defined rate 
of spontaneous KS regression, which is 20%. We chose to evaluate a 20% improvement in 
total response rate because we felt that this would be both a clinically significant 
improvement and at least equivalent to current chemotherapy. Because NFV has many 
fewer toxicities and requires less monitoring, oral administration, and less cost and 
potential for better access compared to chemotherapy, a finding of at least equivalence 
could be considered an improvement over the standard-of-care. Because the cost and 
feasibility of using an all-oral NFV regimen in resource-limited settings would provide a 
significant implementation and access benefit over cytotoxic chemotherapy, we feel 
strongly that NFV should be proven similarly efficacious to current chemotherapy, rather 
than superior to it. Therefore, we have chosen a design with 90% power at a one-sided 10% 
significance level to test the hypothesis that 40% of participants receiving NFV at standard 
followed by high-dosing regimens will be able to attain PR or CR. The null hypothesis is 
that we will fail to detect a response superior to the rate of spontaneous tumor regression 
(20%). Participants from both the international and domestic protocol will contribute to the 
single analysis plan, which is based on HIV status and not site of recruitment. 
Primary objective 
To determine the efficacy of a therapeutic escalation strategy consisting of standard dose 
nelfinavir, followed by high dose nelfinavir, for the treatment of Kaposi sarcoma (KS) 
tumor lesions. The binomial proportion and its exact 95% confidence interval will be used 
to estimate the response rate in the study. With 36 evaluable participants, the null 
hypothesis will be rejected if 11 or more participants respond. Response rates will be 
estimated using the binomial proportion and its exact 95% confidence interval separately 
for HIV positive and HIV negative participants. 
Secondary objectives 
• To evaluate the safety of high dose nelfinavir among participants with KS. 
• The frequency of adverse events and their severity will be tabulated to evaluate 
tolerance of high dose NFV in the treatment of KS in both HIV-negative and HIV-
positive participants. 
• To correlate nelfinavir and the primary active metabolite, M8, concentrations with 
tumor response, antiviral response, and adverse effects in participants with KS. Trough 
nelfinavir/M8 concentrations will be summarized using descriptive statistics and 95% 
confidence intervals. This outcome will also be displayed graphically as a trend in drug 
levels over time. The relationship between dose and drug exposure of nelfinavir/M8 
and the pharmacodynamic effects will be determined using Pearson’s correlation 
coefficient (r2) or appropriate non-parametric statistics for dichotomous and categorical 
variables (e.g., Mann–Whitney U-test or Kruskal-Wallis analysis of variance by ranks). 


 
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• To assess the effect of nelfinavir on KSHV lytic gene expression in tumor tissue. 
Descriptive statistics will be used for changes in the relative abundance of all latent and 
lytic viral mRNA relative to cellular mRNA by expression array, and changes in the 
percentage of cells staining for K8.1 (lytic) and LANA (latency-associated nuclear 
antigen) antigens by immunohistochemistry. Generalized estimating equations will be 
used to evaluate these changes over time. Normalizing transformations will be used as 
needed. 
• To assess the effect of nelfinavir on KSHV copy number in saliva. Prior studies 
demonstrate stability of estimates of herpesvirus shedding rate in mucosal swabs with 
14 or more samples. Therefore, pre-treatment oral samples and oral samples during 
treatment will be collected from each participant. The sampling frequency is irrelevant 
as long as the quantity is sufficient. With 36 participants, a decrease in the proportion 
of participants with detectable KSHV DNA from 50% at baseline to 1% on treatment 
can be detected at the one-sided 0.05 significance level with 0.99 power using 
McNemar's test. 
• 
K8.1 will be measured by immunohistochemistry. A study participant’s K8.1 
expression will be considered to have increased with treatment if the percentage of cells 
with K8.1 staining is at least 20% and has increased at least 50% from baseline 
measures. With 36 study participants, the null hypothesis that the proportion of study 
participants who demonstrate an increase is 1% and can be tested against the alternative 
that it is 20% or greater at the one-sided significance level of 0.10 with power of 0.92 
using the exact test for a single proportion (REF: Chernick MR, Liu CY: The saw-
toothed behavior of power versus sample size and software solutions: single binomial 
proportion using exact methods. The American Statistician 56: 149-155, 2002.) Thus, 
the proportion of study participants who demonstrate an increase in K8.1 expression 
will be estimated using the binomial proportion and its exact 95% confidence interval. 
Exploratory objectives 
• To assess the effect of nelfinavir on KSHV and EBV copy number in PBMC and 
plasma. 
• To assess the effect of nelfinavir on HSV, CMV, and EBV in saliva. 
• KSHV detection in plasma (viremia) and oral shedding will be calculated at baseline 
and on NFV treatment. An analysis will also be performed for shedding of HSV, CMV, 
and EBV. Kaplan-Meier curves will also be created to demonstrate percent of 
participants demonstrating the presence of each of the above viruses in blood and saliva 
as a function of time and stage of treatment. For each herpesvirus and source of samples 
(oral or plasma), the following analyses will be done: 
• McNemar’s chi-square test will be used to evaluate the detection of the herpesvirus 
prior to treatment and during treatment. 
• Generalized estimating equations (GEE) using a binomial distribution will be used to 
evaluate the detection of KSHV in plasma and oral specimens over time. Log10 
transformations will be applied to the viral load data, and the median log viral load will 
be estimated for each participant prior to treatment and at time points post treatment. 
Generalized estimating equations (GEE) will be used to assess change over time with 


 
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respect to these measures. 
10.2 
Sample Size/Accrual Rate 
The study is designed to test the null hypothesis that the response rate is less than or equal 
to 20% against the alternative that it is 40% or greater with 90% power at a one-sided 10% 
significance level which will require a sample size of 36 evaluable participants using the 
exact test for a single proportion3,4. 
The plan is to enroll 18 participants who are HIV-positive and 18 who are HIV-negative, 
at an estimated accrual rate of 1-2 participants/month. Participants from both the 
international and domestic sites will contribute to the single analysis plan, which is based 
on HIV status and not site of recruitment. 
Evaluable participants for all endpoints are defined as participants who meet all the 
eligibility criteria, enroll on the study, and receive at least one dose of treatment. 
Participants who enroll but are not treated will be replaced. 
10.3 
Reporting and Exclusions 
10.3.1 
Evaluation of toxicity – All participants will be evaluable for toxicity from the 
time of their first treatment with nelfinavir. 
10.3.2 
Evaluation of response – All participants included in the study must be assessed 
for response to treatment, even if there are major protocol treatment deviations or 
if they are ineligible. Each participant will be assigned one of the following 
categories: 1) complete response, 2) partial response, 3) stable disease, 4) 
progressive disease, 5) early death from malignant disease, 6) early death from 
toxicity, 7) early death because of other cause, or 9) unknown (not assessable, 
insufficient data). 
All of the participants who met the eligibility criteria (with the possible exception 
of those who received no study medication) should be included in the main 
analysis of the response rate. Participants in response categories 4-9 should be 
considered to have a treatment failure (disease progression). Thus, an incorrect 
treatment schedule or drug administration does not result in exclusion from the 
analysis of the response rate. Precise definitions for categories 4-9 will be 
protocol specific. 
All conclusions should be based on all eligible participants. Subanalyses may 
then be performed on the basis of a subset of participants, excluding those for 
whom major protocol deviations have been identified (e.g., early death due to 
other reasons, early discontinuation of treatment, major protocol violations, etc.). 
However, these subanalyses may not serve as the basis for drawing conclusions 
concerning treatment efficacy, and the reasons for excluding participants from 
the analysis should be clearly reported. The 95% confidence intervals should also 
be provided. 
 


 
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10.4 
Stopping Rule for Feasibility 
The stopping rule is based on an underlying proportion of participants with adverse events 
that require treatment termination of 0.05. Thus, the stopping rule is derived by determining 
the number of participants with adverse events that require treatment termination which 
would occur ≤ 5% of the time of the true underlying rate of treatment terminations due to 
adverse events was 0.05. The trial will be stopped if the number of participants who 
terminate treatment due to adverse events is greater than or equal to X out of N participants: 
X 
N 
2 
3-7 
3 
8-16 
4 
17-28 
5 
29-36 


 
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11.0 
ROLE OF DATA MANAGEMENT 
11.1 
CRF Instructions 
Access to the internet data entry system for this study, Advantage eClinical, and 
instructions for recording of study data on CRFs will be provided by the AMC ODMC at 
www.AIDSCancer.org. Participating institutions are responsible for submitting data and/or 
data forms via Advantage eClinical in accordance with the AMC Data Entry Guide and 
specific form instructions, within the timelines specified by the AMC’s Standards of 
Procedure for Site Performance Measures. 
11.2 
Data Quality 
It is the responsibility of the AMC ODMC to assure the quality of data for the study (See 
Appendix VI, AMC Data and Safety Monitoring Plan). This role extends from protocol 
development to generation of the final study database. 
11.3 
Data Monitoring 
This study will be monitored in compliance with AMC policies and by the Clinical Data 
Update System (CDUS) Version 3.0. Cumulative protocol- and participant-specific CDUS 
data will be submitted electronically to CTEP on a quarterly basis. Reports are due January 
31, April 30, July 31, and October 31. Instructions for submitting data using the CDUS can 
be found on the CTEP Web site (http://ctep.cancer.gov/reporting/cdus.html). The AMC 
ODMC is responsible for compiling and submitting CDUS data to CTEP for all participants 
and for providing the data to the Principal Investigator for review. 


 
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12.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
12.1 
IRB Approval and Informed Consent 
The principles of Institutional Review Board (IRB) approval and informed consent 
described in the Food and Drug Administration (FDA) regulations (21 CFR Part 50 and 
56) and Department of Health and Human Services (DHHS) regulations for the Protection 
of Human Subjects regulations (45 CFR Part 46) must be followed. IRB approval of the 
protocol and the informed consent form must be given in writing. 
The sponsor’s designee (AMC ODMC) must receive a copy of the letter of approval from 
the IRB, which specifically approves the protocol and informed consent, before participant 
enrollment. The IRB must also approve any significant changes to the protocol and 
documentation of this approval must be sent to the AMC ODMC. The IRB must review 
the research project at least once every 365 days during the duration of the project. 
Continuing approval of the project must also be given in writing and provided to the AMC 
ODMC. 
Records of all study review and approval documents must be kept on file by the 
Investigator and are participant to inspection during or after completion of the study. AEs 
must be reported to the IRB according to local procedures. The IRB should receive 
notification of completion of the study and final report within 3 months of study completion 
and termination. The Investigator will maintain an accurate and complete record of all 
submissions made to the IRB, including a list of all reports and documents submitted. 
Written informed consent will be obtained from the participant. The nature and significance 
of the risks associated with the study must be explained to the participant. The informed 
consent will describe the purpose of the study, the procedures to be followed, the risks and 
benefits of participation, all risks of the investigational agent(s) and/or study participation 
as listed in the model informed consent form, and all other elements of informed consent 
as required by regulation. A copy of the consent form will be given to the participant to 
keep. 
In addition, any institution(s) conducting research according to the guidelines of this 
protocol is required to adhere to local and national laws and regulations governing the 
confidentiality and disclosure of health information. 
12.2 
Changes to the Protocol 
Any change or addition to this protocol requires a written protocol amendment that must 
be approved by CTEP and the Investigator before implementation. All amendments require 
approval by the IRB/IEC of the treating institution. A copy of the written approval of the 
IRB/IEC and the national regulatory body (if applicable) must be sent to the ODMC. 
12.3 
Women and Minorities 
This study is being conducted by the NCI-sponsored AIDS Malignancy Consortium 
(AMC). As part of their contractual obligations, each participating site within the AMC 
and the AMC as a whole is required to assure that the participation of women and minority 
participants reflects the percentage representation of these populations in their geographic 
region and, for the AMC, the United States as a whole. As such, it is expected that the 
representation of participants on this trial will reflect the constitution of the respective 


 
AMC 098 (Version 4.0) 08DEC2020 
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populations. 
Accrual Targets 
DOMESTIC PLANNED ENROLLMENT REPORT 
Racial Categories 
Ethnic Categories 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
American Indian/ Alaska Native 
0 
0 
0 
0 
0 
Asian 
0 
0 
0 
0 
0 
Native Hawaiian or Other Pacific 
Islander 
0 
0 
0 
0 
0 
Black or African American 
3 
12 
0 
1 
16 
White 
1 
5 
1 
3 
10 
More Than One Race 
0 
0 
0 
0 
0 
Total 
4 
17 
1 
4 
26 
 
INTERNATIONAL PLANNED ENROLLMENT REPORT 
Racial Categories 
Ethnic Categories 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
American Indian/ Alaska Native 
0 
0 
0 
0 
0 
Asian 
0 
0 
0 
0 
0 
Native Hawaiian or Other Pacific 
Islander 
0 
0 
0 
0 
0 
Black or African American 
3 
7 
0 
0 
10 
White 
0 
0 
0 
0 
0 
More Than One Race 
0 
0 
0 
0 
0 
Total 
3 
7 
0 
0 
10 
 
 
 


 
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12.4 
Investigator and Research Associate Registration with CTEP 
Food and Drug Administration (FDA) regulations and National Cancer Institute (NCI) 
policy require all individuals contributing to NCI-sponsored trials to register and to renew 
their registration annually. To register, all individuals must obtain a Cancer Therapy 
Evaluation Program (CTEP) Identity and Access Management (IAM) account at 
https://ctepcore.nci.nih.gov/iam. In addition, persons with a registration type of 
Investigator (IVR), Non-Physician Investigator (NPIVR), or Associate Plus (AP) (i.e., 
clinical site staff requiring write access to the electronic data entry system for this protocol 
or acting as a primary site contact) must complete their annual registration using CTEP’s 
web-based 
Registration 
and 
Credential 
Repository 
(RCR) 
at 
https://ctepcore.nci.nih.gov/rcr.  
RCR utilizes five-person registration types. 
• IVR: MD, DO, or international equivalent, 
• NPIVR: advanced practice providers (e.g., NP or PA) or graduate level researchers 
(e.g., PhD), 
• AP: clinical site staff (e.g., RN or CRA) with data entry access to CTSU and/or AMC 
applications (e.g., Roster Update Management System [RUMS], OPEN, Rave; 
Advantage eClinical for this protocol), 
• Associate (A): other clinical site staff involved in the conduct of NCI-sponsored trials, 
and 
• Associate Basic (AB): individuals (e.g., pharmaceutical company employees) with 
limited access to NCI-supported systems. 
Table 12-B: CTEP investigator registration documentation requirements 
Documentation Required 
IVR 
NPIVR 
AP 
A 
FDA Form 1572 
 
 
 
 
Financial Disclosure Form 
 
 
 
 
NCI Biosketch (education, training, employment, 
license, and certification) 
 
 
 
 
HSP/GCP training 
 
 
 
 
Agent Shipment Form (if applicable) 
 
 
 
 
CV (optional) 
 
 
 
 
An active CTEP-IAM user account and appropriate RCR registration is required to access 
all CTEP and Cancer Trials Support Unit (CTSU) websites and applications. In addition, 
IVRs and NPIVRs must list all clinical practice sites and IRBs covering their practice sites 


 
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on the FDA Form 1572 in RCR to allow the following: 
• Added to a site roster 
• Act as the site-protocol PI on the IRB approval 
• Assigned the Clinical Investigator (CI) role on the Delegation of Tasks Log (DTL; the 
AMC DTL template will be used for this study; see Section 12.5). 
Additional 
information 
can 
be 
found 
on 
the 
CTEP 
website 
at 
https://ctep.cancer.gov/investigatorResources/default.htm. For questions, please contact 
the RCR Help Desk by email at RCRHelpDesk@nih.gov. 
12.5 
Protocol Registration and Delegation of Tasks Log 
Each site must complete a protocol-specific registration packet, including an AMC DTL 
using the provided AMC template or local equivalent. The Clinical Investigator (CI) is 
required to review and sign the AMC DTL prior to the site receiving an approved site 
registration status and enrolling participants to the study. The AMC DTL template is 
provided in the protocol registration packet for this protocol, located on the AMC 
Operations web site at www.AIDSCancer.org. Any individual at the enrolling site on a 
participating roster may initiate the site DTL. Instructions on completing the DTL are 
embedded in the AMC DTL template. 
The AMC DTL must be updated contemporaneously as personnel are added or removed 
and/or study roles and delegated tasks change. Changes must be approved by the CI, and 
documented by his/her initials and date, before they are implemented. 
 


 
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13.0 
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30. Fife K, et al. (1999) Cidofovir for the treatment of Kaposi's sarcoma in an HIV-negative 
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34. El Amari EB, et al. (2008) Predicting the evolution of Kaposi sarcoma, in the highly active 
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35. Little RF, et al. (2003) A pilot study of cidofovir in patients with Kaposi sarcoma. J Infect 
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36. Gills JJ, Lopiccolo J, & Dennis PA (2008) Nelfinavir, a new anti-cancer drug with pleiotropic 
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37. Gills JJ, et al. (2007) Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, 
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38. Bernstein WB & Dennis PA (2008) Repositioning HIV protease inhibitors as cancer 
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42. Pujades-Rodriguez M, O'Brien D, Humblet P, & Calmy A (2008) Second-line antiretroviral 
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43. Sanne I, Piliero P, Squires K, Thiry A, & Schnittman S (2003) Results of a phase 2 clinical 
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44. Idoko JA, et al. (2002) A multicentre study to determine the efficacy and tolerability of a 
combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the 
treatment of HIV infected Nigerian patients. West Afr J Med 21(2):83-86. 
45. Kilewo C, et al. (2009) Prevention of mother-to-child transmission of HIV-1 through 
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Tanzania: the Mitra Plus study. J Acquir Immune Defic Syndr 52(3):406-416. 
46. Pan J, et al. (2012) Phase I study of nelfinavir in liposarcoma. Cancer Chemother Pharmacol. 
47. Gantt S, Casper C, & Ambinder RF (2013) Insights into the Broad Cellular Effects of 
Nelfinavir and the HIV Protease Inhibitors Supporting their Role in Cancer Treatment 
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48. Bono C, et al. (2012) The human immunodeficiency virus-1 protease inhibitor nelfinavir 
impairs proteasome activity and inhibits the proliferation of multiple myeloma cells in 
vitro and in vivo. Haematologica 97(7):1101-1109. 
49. Chow WA, Jiang C, & Guan M (2009) Anti-HIV drugs for cancer therapeutics: back to the 
future? Lancet Oncol 10(1):61-71. 
50. Pore N, et al. (2006) Nelfinavir down-regulates hypoxia-inducible factor 1alpha and VEGF 
expression and increases tumor oxygenation: implications for radiotherapy. Cancer Res 
66(18):9252-9259. 
51. Lan X, et al. (2012) The effect of HIV protease inhibitors on amyloid-beta peptide 
degradation and synthesis in human cells and Alzheimer's disease animal model. J 
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52. Chow WA, Guo S, & Valdes-Albini F (2006) Nelfinavir induces liposarcoma apoptosis and 
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53. Guan M, et al. (2011) Nelfinavir induces liposarcoma apoptosis through inhibition of 
regulated intramembrane proteolysis of SREBP-1 and ATF6. Clin Cancer Res 
17(7):1796-1806. 
54. Kalu NN, et al. (2014) Nelfinavir inhibits maturation and export of herpes simplex virus 1. 
J Virol 88(10):5455-5461. 
55. Gantt S, et al. (2011) The HIV protease inhibitor nelfinavir inhibits Kaposi's sarcoma-
associated herpesvirus replication in vitro. Antimicrob Agents Chemother 55(6):2696-
2703. 
56. Gantt S, et al. (2014) Reduced human herpesvirus-8 oropharyngeal shedding associated with 
protease inhibitor-based antiretroviral therapy. J Clin Virol 60(2):127-132. 
57. Gantt S, et al. (2015) Nelfinavir impairs glycosylation of herpes simplex virus 1 envelope 
proteins and blocks virus maturation. Adv Virol 2015:687162. 
58. Mosam A, et al. (2012) A randomized controlled trial of highly active antiretroviral therapy 
versus highly active antiretroviral therapy and chemotherapy in therapy-naive patients 
with HIV-associated Kaposi sarcoma in South Africa. J Acquir Immune Defic Syndr 
60(2):150-157. 
59. Gbabe OF, Okwundu CI, Dedicoat M, & Freeman EE (2014) Treatment of severe or 
progressive Kaposi's sarcoma in HIV-infected adults. Cochrane Database Syst Rev 
9:CD003256. 
60. Cianfrocca M, et al. (2010) Randomized Trial of Paclitaxel Versus Pegylated Liposomal 
Doxorubicin for Advanced Human Immunodeficiency Virus-Associated Kaposi 
Sarcoma Evidence of Symptom Palliation from Chemotherapy. Cancer 116(16):3969-
3977. 
61. Uldrick TS, et al. (2013) Phase I and pharmacokinetic study of sorafenib in Kaposi sarcoma. 
Journal of Clinical Oncology 31(15). 
62. Uldrick TS, et al. (2012) Phase II Study of Bevacizumab in Patients With HIV-Associated 
Kaposi's Sarcoma Receiving Antiretroviral Therapy. Journal of Clinical Oncology 
30(13):1476-1483. 
63. Lechowicz M, et al. (2009) Molecular and Clinical Assessment in the Treatment of AIDS 
Kaposi Sarcoma with Valproic Acid. Clinical Infectious Diseases 49(12):1946-1949. 
64. Rudek MA, et al. (2014) A phase 1/pharmacokinetic study of sunitinib in combination with 
highly active antiretroviral therapy in human immunodeficiency virus-positive patients 
with cancer: AIDS Malignancy Consortium trial AMC 061. Cancer 120(8):1194-1202. 
65. Casado JL, et al. (2001) Efficacy, tolerance, and pharmacokinetics of the combination of 
stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or 
indinavir failure. AIDS Res Hum Retroviruses 17(2):93-98. 
66. Moyle GJ, et al. (1998) Safety, pharmacokinetics, and antiretroviral activity of the potent, 
specific human immunodeficiency virus protease inhibitor nelfinavir: Results of a phase 
I/II trial and extended follow-up in patients infected with human immunodeficiency 
virus. J Clin Pharmacol 38(8):736-743. 
67. Anonymous (1997) Anti-HIV effects of nelfinavir reported after ten months of combination 
therapy. AIDS Patient Care STDS 11(4):289-290. 
 


 
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APPENDIX I: SCHEDULE OF PROCEDURES 
The schedule of evaluations below applies to all participants on study. Baseline evaluations (including scans and x-rays) are to be 
conducted within 4 weeks prior to study enrollment into Segment B (Treatment Enrollment), unless specified below. 
Assessment Type 
Study 
Stage 
Baseline/ 
Screening 
Treatment 
Start 
SD-NFV1 
HD-NFV1 
Early Discontinuation 
and Follow-Up 
Study 
Visit 
Up to 4 Weeks 
Before NFV 
Unless Noted 
Treatment 
Day 0 
Every 2 Weeks 
Through Week 8 
Unless Noted 
Every 2 Weeks 
Through Week 24 
Unless Noted 
Within 7 Days After 
Stopping NFV for Early 
Disc. 
+8 Weeks (± 3 days) After 
Stopping NFV for 
Follow-Up 
Informed Consent (2 to 4 weeks before NFV) 
X 
 
 
 
 
Optional ACSR Donation 
X 
 
 
 
 
Demographics, Height, Diagnostic KS 
Biopsy2, ECOG/KPS score 
 
X 
 
 
 
 
Medical History (including documentation 
of HIV diagnosis if positive), Concurrent 
meds, Physical Exam, Vital Signs, Weight 
 
X 
 
X 
X 
X 
Confirmatory HIV Test if Previously HIV-
negative 
 
X 
 
 
 
 
Chest X-Ray 
 
X 
 
X7 
X7 
X7 
CBC w/ Differential 
Safety Labs/Chemistries: calcium, sodium, 
potassium, CO2, chloride, AST 
(SGOT)/ALT(, SGPT), BUN, creatinine, 
direct and total bilirubin, fasting glucose, 
and triglycerides. 
 
X 
 
 
X (every 4 wks.) 
X 
Fasting Glucose and Triglycerides 
 
X 
 
 
X (every 8 wks.) 
X 


 
AMC 098 (Version 4.0) 08DEC2020 
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Assessment Type 
Study 
Stage 
Baseline/ 
Screening 
Treatment 
Start 
SD-NFV1 
HD-NFV1 
Early Discontinuation 
and Follow-Up 
Study 
Visit 
Up to 4 Weeks 
Before NFV 
Unless Noted 
Treatment 
Day 0 
Every 2 Weeks 
Through Week 8 
Unless Noted 
Every 2 Weeks 
Through Week 24 
Unless Noted 
Within 7 Days After 
Stopping NFV for Early 
Disc. 
+8 Weeks (± 3 days) After 
Stopping NFV for 
Follow-Up 
Adherence Review Nutrition Assess. KS 
Sign/Symp. Assessment 
 
X 
 
X 
X 
X3 
KS Staging 
 
X 
 
 
 
 
Standardized Assessment of Tumor 
Response with Photographs 
 
 
X8 
X 
X 
X 
If HIV-positive: CD4 Count, and % 
 
X 
 
 
 
X 
If HIV-positive: HIV Plasma Viral Load 
 
X 
 
X (every 8 wks.) 
X (every 8 wks.) 
X 
beta-HCG if of Childbearing Potential 
 
X 
X5 
 
X5 
 
EKG 
 
X 
 
X6 
X6 
 
Provide and Review Drug Diary, Provide 
Study Drug, and Nutritional Counseling 
 
 
X 
X4 
X4 
 
Provide Participant Instructions for Oral 
swabs 
 
X 
 
 
X4 (once after 
starting HD-NFV) 
 
1. Study weeks and timing of standard dose nelfinavir (SD-NFV) and high dose nelfinavir (HD-NFV) may vary based on response; see Section 4.1. Scheduled 
study visits will be every 2 weeks +/- 3 days. Sufficient drug to provide continuous dosing between cycles/study visits should be provided as long as visits lie 
within the visit window. 
2. Can be the same biopsy collected for immunohistochemistry correlative studies. May be performed any time prior to study enrollment. 
3. Medication adherence review and nutrition assessment not required at Early Discontinuation or Follow-up visit. 
4. Providing drug diary, study drug, participant instructions for oral swabs, and nutritional counseling not required if participant is discontinued. 
5. Pregnancy testing for females of childbearing potential immediately prior to starting SD-NFV (day 0) and again immediately prior to starting HD-NFV. 
6. EKG only required once 2 weeks after starting SD-NVF and once 2 weeks after starting HD-NFV. 


 
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7. A chest X-Ray should be performed to evaluate tumor response only for participants with pulmonary KS or new pulmonary symptoms. 
8. Tumor assessment with photographs may be performed on Day 0, but no earlier than 7 days before initiating study treatment. 


 
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APPENDIX II: BIOMARKERS AND CORRELATIVE STUDIES 
Sample 
Collected in 
Baseline/Screening 
Weeks 
-4 to 0 
Treatment start/ 
Day 0 
SD-NFV1 
HD-NFV1 
Special Handling 
Where to 
Send 
3mm skin biopsies for 
immunohistochemistry 
expression of LANA 
and 3 lytic gene 
products; KSHV gene 
expression arrays 
1 biopsy in 
formalin (for 
IHC); 1 biopsy in 
RNAlater (for 
gene expression) 
Weeks -4 to 0, once 
-- 
2 weeks after 
starting SD-NFV 
2 weeks after starting 
HD-NFV 
See 
Appendix X 
See 
Appendix X 
Whole blood for 
separation into plasma 
and PBMCs for KSHV 
and EBV qPCR 
One 8.5 ml ACD 
(yellow top) tube 
2 total blood 
samples during 
weeks 
-4 to 0 
-- 
-- 
Each visit 
(every 2 weeks) after 
starting HD-NFV 
(8 samples total) 
See 
Appendix X 
See 
Appendix X 
Oral swabs for KSHV, 
EBV, CMV, and HSV  
Study-specific 
swabs/tubes 
14 total daily 
swabs, collected 
during weeks -4 to 
0 
-- 
-- 
2 swabs per week 
while on HD-NFV 
for a total of 14 
swabs 
Stored at room 
temperature. Ship in 
batches bi-weekly 
(Sun-Wed); 
See 
Appendix X 
Genotyping 
To be performed 
using DNA from 
PBMC 
Once 
-- 
-- 
-- 
See 
Appendix X 
See 
Appendix X 
Peripheral blood for 
PK 
~6 ml of whole 
blood processed as 
plasma (one 6 ml 
potassium EDTA 
lavender top tube) 
-- 
Immediately (- 3 days) pre-dose at each visit (every 2 weeks) 
starting on Week 1/cycle 1 through the completion of Week 
15/cycle 9 (9 total samples) 
Stored on ice, 
plasma separated 
within 30 minutes 
and frozen at ~ -70. 
Ship in batches 
(Mon-Wed) 
See 
Appendix 
IX 
1. 
Study weeks and timing of SD-NFV and HD-NFV may vary based on response; see Section 4.1. Scheduled study visits will be every 2 weeks. 
 
 


 
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APPENDIX III: PERFORMANCE STATUS SCALES 
Karnofsky Performance Scale 
ECOG Performance Status Scale 
Percent 
Description 
Grade 
Description 
100 
Normal, no complaints, no 
evidence of disease. 
0 
Normal activity. Fully active, able 
to carry on all pre-disease 
performance without restriction. 
90 
Able to carry on normal activity; 
minor signs or symptoms of 
disease. 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
1 
Symptoms, but ambulatory. 
Restricted in physically strenuous 
activity, but ambulatory and able to 
carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
70 
Cares for self, unable to carry on 
normal activity or to do active 
work. 
60 
Requires occasional assistance but 
is able to care for most of his/her 
needs. 
2 
In bed < 50% of the time. 
Ambulatory and capable of all self-
care, but unable to carry out any 
work activities. Up and about more 
than 50% of waking hours. 
50 
Requires considerable assistance 
and frequent medical care. 
40 
Disabled, requires special care 
and assistance. 
3 
In bed > 50% of the time. Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
30 
Severely disabled, hospitalization 
indicated. Death not imminent. 
20 
Very sick, hospitalization 
indicated. Death not imminent. 
4 
100% bedridden. Completely 
disabled. Cannot carry on any self-
care. Totally confined to bed or 
chair. 
10 
Moribund, fatal processes 
progressing rapidly. 
0 
Dead. 
5 
Dead. 
 


 
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APPENDIX IV: AIDS AND CANCER SPECIMEN RESOURCE (ACSR) SPECIMEN 
PREPARATION AND SHIPPING INSTRUCTIONS 
A. 
GENERAL 
To ship blood specimens, use a diagnostic shipper approved for a volume of at least 30 cc. 
The use of the SAF-T-PAK STP 210 diagnostic cardboard shipper is recommended. These 
shippers may be ordered at the SAF-T-PAK website: www.saftpak.com. The following 
instructions below are for use with the recommended STP-210 shipper. If using another 
federally approved diagnostic shipper, please follow instructions provided for that specific 
shipper. 
NOTE: Specimens MUST BE SHIPPED Mondays through Thursdays an OVERNIGHT 
PRIORITY shipment. Specimens are NOT ACCEPTED ON SATURDAYS OR 
SUNDAYS in the ACSR. 
B. 
SPECIMEN PREPARATION, PACKAGING, AND SHIPMENT 
Blood specimens 
Draw two 8.5 cc (mL) yellow top [acid citrate dextrose (ACD)] tubes from study 
participant. With a black, water resistant, sharpie pen, label each specimen with the 
following information: 
• AMC Protocol # 098 
• AMC Participant ID# 
• Date and time of collection 
• Specimen type, i.e., WB=Whole Blood, P=Plasma, S=Serum, or Tissue 
• Specimen purpose: Donation 
Specimen shipment 
• Seal the tops of the two 8.5 cc yellow tops with Parafilm. 
• Place the two sealed tubes into bubble wrap (provided in STP-210 kit). 
• Tape around the bubble wrap so that the roll stays together and the tubes cannot fall 
out or break. 
• Place absorbent material sheet around the bubble wrapped tubes and slip into a 
biohazard poly-bag and “self-seal.” 
• Place poly-bag containing tubes into the white TYVEK bag and seal. 
• Place the TYVEK bag into the STP-210 diagnostic cardboard shipper. Seal the 
cardboard shipper with clear packing/shipping tape. 
• Affix the FED-EX air bill on blank side of the shipper making sure that it is marked 
“FED-EX PRIORITY OVERNIGHT.” 
• Mark “OTHER” in the air bill under “Packaging.” Please use the FedEx # available on 
the AMC member’s only website. 


 
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• Under air bill section “Special Handling” indicate “YES-SHIPPERS DECLARATION 
NOT REQUIRED.” 
• Place “From/To” information onto areas provided on the shipper. 
Blood specimens should be shipped by overnight express at room temperature to: 
Sylvia Silver, DA 
AMC Biorepository 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: 202-994-2945 
Fax: 202-994-5056 
Email: ssilver@gwu.edu 
• Make certain that shipper is already either pre-labeled with ‘UN#3373’ stamp or make 
a paper label with ‘UN#3373” and affix it to the shipper. 
• Make certain that the net volume of the specimen being shipped is written in the space 
provided on the shipper or make a separate label with the volume in ml and affix to the 
shipper. 
• Affix air bill to shipper so that the ‘UN’ and ‘VOLUME’ labels are visible. 
• RETAIN THE TOP COPY OF THE AIRWAY BILL FOR YOUR RECORDS. 
• Place the box in the FedEx pickup area at your site or call to request a package pickup. 
Please Note: The shippers will be mailed back to each AMC site. 
INSTRUCTIONS FOR BLOOD SPECIMENS COLLECTED ON FRIDAY OR 
SATURDAY 
Preparation of plasma and mononuclear cells 
Refer to the ACSR’s Standard Operating Procedure (SOP) on Separation of Plasma and 
Mononuclear Cells on the AMC Operations web site for instructions on preparing plasma 
and PBMC aliquots. It is preferable that separation occurs as soon as possible. If necessary, 
whole blood in ACD (yellow top tubes) can be held at room temperature for no more than 
24 hours. 
Freeze the cell suspension in 0.5 mL aliquots in sterile NUNC vials by placing the NUNC 
tubes in a room temperature, alcohol saturated, control rate freezer container and store in 
the -80°C freezer overnight. Transfer the cell suspension into the liquid nitrogen 
temperature freezer for long-term storage the next working day. 
***PLEASE DOUBLE CHECK PACKAGING OF SHIPPER AND DO NOT 
DEVIATE FROM REQUESTED LABELING. Shipping frozen aliquots requires the 
use of packaging acceptable for dry ice and Class 9 label with weight of dry ice written 
on package. 


 
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Preparation of tissue samples 
Tissue specimens to be fresh frozen should be placed in OCT and then on dry ice 
immediately. The specimens may stay on dry ice until being transferred to a -80ºC freezer. 
Tissue specimens for donation may be batched for shipping after storage in -80ºC freezer. 
*NOTE: Specimens can only be accepted Monday through Friday. Therefore, specimens 
can only be shipped Sunday-Thursday for delivery the next day. Shipping frozen tissue 
requires the use of packaging acceptable for dry ice and Class 9 label with weight of dry 
ice written on package. 
TISSUE specimens should be shipped by overnight express to: 
Sylvia Silver, DA 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: 202-994-2945 
Fax: (202) 994-5056 
C. 
RECORD OF SPECIMENS 
This study will track specimens via GlobalTraceSM, a component of the AMC Advantage 
eClinical system. The GlobalTrace shipment manifest must accompany all specimen 
shipments. 


 
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APPENDIX V: ACSR INFORMED CONSENT 
Study Title for Study 
Participants: 
Collecting Blood and Tissue Sample Donations for 
Research for HIV/AIDS-Related Cancers 
Official Study Title: 
Biospecimen Collection and Donation to the AIDS  
and Cancer Specimen Resource (ACSR) 
What is the usual approach to donate blood and/or tissue to the ACSR? 
You are being asked to donate blood and/or tissue for future research. You are being asked to 
donate your blood and/or tissue samples to the ACSR because you have HIV infection and are 
being considered for participation in an AIDS Malignancy Consortium (AMC) clinical trial. The 
AMC works with the ACSR to collect donated samples from persons with HIV infection for 
research studies. People who do not take part in an AMC clinical trial can also donate samples to 
the ACSR. 
What are my other choices if I do not take part in this study? 
It is your choice to donate or not donate your blood and/or tissue samples. You may still take part 
in the AMC clinical study if you choose not to donate blood or biopsy samples to the ACSR.  
You may also choose to donate: 
• Blood but not tissue, or 
• Tissue but not blood. 
What is the AIDS and Cancer Specimen Resource (ACSR)? 
The ACSR is a biorepository (biobank) that collects human biological specimens (samples) from 
persons who have HIV or cancers related to HIV/AIDS. The ACSR stores the samples and some 
of the donor’s medical information for use by researchers in future research studies. The National 
Cancer Institute (NCI) has set up the ACSR to assist researchers locate samples needed for their 
studies. 
The ACSR has an independent research panel that approves researchers’ requests to use the 
ACSR’s stored samples for research studies. The ACSR only gives samples and medical 
information to researchers after their projects have been approved. Researchers may use the 
samples to study cancers and other diseases associated with HIV disease. This information may 
help us learn more about the causes of HIV-related diseases and cancers and to develop better 
ways to screen, diagnose, and treat them. 
Why is this study being done? 
The purpose of this study is to collect samples for the ACSR for future research studies. 
Researchers may study samples from the ACSR in combination with hundreds or thousands of 
other samples to explore how biologic or genetic factors may be related to HIV-related diseases 
and cancer. The information might help doctors in the future to identify who will or will not benefit 
from treatment. The samples may be used to learn more about how HIV-related diseases and 
cancers develop. The samples may also lead to new tests or discoveries. Finally, researchers may 
use the samples to study the genetic material from your cancer tissue and compare it to the material 
from your normal tissue (blood) to try to find the differences that exist. These studies could make 
it possible to identify many of the changes that are associated with diseases such as cancers. It may 


 
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also help us tailor treatments to a patient's unique genetic make-up and/or to the genetic markers 
of the tumors. 
What extra tests and procedures will I have if I take part in this study? 
1) If you agree to donate blood, the medical team will draw about 2 tablespoons of blood to give 
to the ACSR. This takes about 10 minutes. 
2) If you agree to donate tissue, your leftover tissue biopsy material will be donated to and stored 
by the ACSR. 
3) Some of your clinical information will be released to the ACSR and entered into their database. 
The information given to the ACSR will not include your name or any information that could 
personally identify you. 
We will only give the ACSR tissue that is left over after making decisions about your treatment or 
diagnosis. The study doctor will not take any extra biopsies just for the ACSR. 
We cannot tell you right now what future research these samples would be used for. Instead, we 
are asking that you give approval to give your samples for future testing without contacting you 
again. The results of whatever research is done on your samples will not be told to you or your 
doctor. The results of the tests will not be placed in your study records. 
How long will ACSR keep my samples? 
Your blood and/or tissue sample will be stored until it is used for research. The samples may be 
stored indefinitely. 
What possible risks can I expect from taking part in this study? 
• Blood Draw: The risks of drawing blood include temporary discomfort from the needle stick, 
bruising, and, rarely, infection. 
• Confidentiality: The ACSR will receive study samples with code numbers. There will be no 
personal identifiers on the samples. Then the samples will be re-labeled with a barcode and 
stored for future testing. While the ACSR and researchers who study ACSR samples will have 
no information that could identify you, there is a risk that someone could use information from 
genetic studies to trace your samples back to you. The researchers believe the chance that 
someone will identify you is very small, but the risk may change in the future as people come 
up with new ways of tracing information. In some cases, this information could be used to 
make it harder for you to get or keep a job. There are laws against misuse of genetic 
information, but they may not give full protection. The researchers believe the chance these 
things will happen is very small but cannot promise that they will not occur. 
Let your study doctor know of any questions you have about these possible risks. You can ask the 
study doctor questions about side effects at any time. 
What possible benefits can I expect from taking part in this study? 
This study is unlikely to help you. This study may help us learn things that may help people in the 
future. 
The information may help to identify those who are at increased risk and those who may benefit 
from targeted treatment and screening. In turn, these studies could help find ways to prevent or 
improve treatments for HIV-related diseases and AIDS-related cancers. 


 
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Can I stop taking part in this study? 
Yes, you may withdraw your samples from the ACSR at any time. You may contact your AMC 
study coordinator if you would like to withdraw your samples. The coordinator can ask in writing 
that your sample be removed from research use and that any identifiable sample and information 
still in their possession be destroyed. However, if any research has already been done using some 
of your samples, the data will be kept and analyzed as part of those studies. 
What are my rights in this study? 
Taking part in this study is your choice. No matter what decision you make, and even if your 
decision changes, there will be no penalty to you. You will not lose medical care or any legal 
rights. 
For questions about your rights while in this study, call the ________________________ (insert 
name of center) Institutional Review Board at __________________ (insert telephone number). 
(Note to Local Investigator: Contact information for patient representatives or other individuals 
at a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can also be listed here.) 
What are the costs of taking part in this study? 
There will be no cost to you for donating your samples to the ACSR. You will not be paid for 
taking part in this study. 
What happens if I am injured or hurt because I took part in this study? 
If you are injured or hurt as a result of taking part in this study and need medical treatment, please 
tell your study doctor. The AMC will not offer to pay for medical treatment for injury. Your 
insurance company may not be willing to pay for study-related injury. If you have no insurance, 
you would be responsible for any costs. 
If you feel this injury was a result of medical error, you keep all your legal rights to seek payment 
for injury even though you are in a study. 
Who will see my medical information? 
Your privacy is very important to us and the researchers will make every effort to protect it. Your 
information may be given out if required by law. For example, certain states require doctors to 
report to health boards if they find a disease like tuberculosis. However, the researchers will do 
their best to make sure that any information that is released will not identify you. Some of your 
health information, and/or information about your specimen, from this study will be kept in a 
central database for research. Your name or contact information will not be put in the database. 
There are organizations that may inspect your records. These organizations are required to make 
sure your information is kept private, unless required by law to provide information. Some of these 
organizations are: 
• The AIDS Malignancy Consortium (AMC) 
• The Institutional Review Board, IRB, is a group of people who review the research with the 
goal of protecting the people who take part in the study. 
• The Office for Human Research Protections and the National Cancer Institute in the U.S. 


 
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To protect your privacy, the AMC does not keep identifying information that links study 
participants to specific samples. As a result, the AMC and ACSR will not be able to link the results 
from studies that use your samples back to you. Thus, information, including genetic information, 
that researchers may obtain in studies that use your samples may not be directly linked to you and 
will not be placed in your medical record. However, some clinical and basic information obtained 
confidentially from the AMC will be attached with these data. It is possible that findings may one 
day help, for example, people of the same race or sex as you. It also is possible that genetic factors 
might come to be associated with people who have HIV and cancer through these kinds of studies. 
Where can I get more information? 
You may visit the NCI Web site at http://cancer.gov/ for more information about studies or 
general information about cancer. You may also call the NCI Cancer Information Service to get 
the same information at 1-800-4-CANCER (1-800-422-6237). 
Who can answer my questions about this study? 
You can talk to the study doctor about any questions or concerns you have about this study or to 
report side effects or injuries. Contact the study doctor __________________ (insert name of study 
doctor[s]) at __________________ (insert telephone number). 
Please circle your answer to show whether or not you would like to take part in each option: 
1) I agree to donate my blood to the ACSR for future research that may be used to learn about, 
prevent, diagnose, or treat HIV-related diseases and cancer. 
YES 
NO 
2) I agree to donate my blood to the ACSR for future research that may include genetic testing to 
learn about, prevent, diagnose, or treat HIV-related diseases and cancer. 
YES 
NO 
3) I agree to donate some of my tissue biopsy material that is not required for my treatment or 
diagnosis to the ACSR for future research that may be used to learn about, prevent, diagnose, 
or treat HIV-related diseases and cancer. 
YES 
NO 
4) I agree to donate some of my tissue biopsy material to the ACSR for future research that may 
include genetic testing to learn about, prevent, diagnose, or treat HIV-related diseases and 
cancer. 
YES 
NO 


 
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My Signature Agreeing to Take Part in The Study 
I have read this consent form or had it read to me. I have discussed it with the study doctor and my 
questions have been answered. I will be given a signed copy of this form. I agree to take part in 
the optional study.  
 
Participant’s signature________________________________ 
 
Date of signature_____________________________________ 
 
Signature of person(s) conducting the informed consent discussion________________________ 
 
Date of signature_____________________________________ 


 
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APPENDIX VI: AMC DATA AND SAFETY MONITORING PLAN 
(Version 9.0  October 6, 2020) 
 
Introduction 
The AIDS Malignancy Consortium (AMC) Data and Safety Monitoring Plan (DSMP) outlines the 
measures employed by the group to monitor the safety of participants and ensure the data validity 
and integrity for all clinical trials it conducts. This includes methods to: 1) monitor the progress of 
trials and the safety of participants; 2) comply with regulatory requirements for adverse event (AE) 
reporting; 3) processes for trial termination or temporary suspension and major modifications; and 
4) plans for ensuring data accuracy and protocol compliance. As the AMC conducts protocols of 
varying research phase, region of conduct (which may include trials conducted in the U.S., 
international sites, or both), IND sponsor (AMC investigator, CTEP, or industry-sponsored) and 
clinical data entry system use, this plan addresses broad processes applying to the range of trial 
designs and requirements. Refer to the individual AMC protocol to identify the applicable study 
characteristics for the relevant requirements described in this plan. 
Monitoring the Progress of Trials and the Safety of Participants 
Routine and expedited AE reporting 
All AMC protocols that collect safety data adhere to the National Cancer Institute (NCI), Cancer 
Therapy Evaluation Program (CTEP) Guidelines: Adverse Event Reporting Requirements 
(https://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm), as applicable to the clinical 
protocol. AEs are to be recorded in the source documents, assessed by a clinical investigator for 
the AE reporting criteria, and promptly reported in the clinical data entry system as required by 
each protocol. For AMC trials conducted under a CTEP IND and AMC trials conducted within the 
U.S., all AEs that meet the NCI’s expedited reporting requirements are reported to the NCI via the 
CTEP Adverse Event Reporting System (CTEP-AERS) web application, either directly or through 
integration with Medidata Rave where this system is employed for AMC protocols. Use of this 
system ensures notification to the protocol chair and Investigational Drug Branch (IDB) at CTEP, 
as required for trials conducted under a CTEP IND, and a uniform expedited reporting and safety 
review process for AMC domestic trials. The system may also be programmed to include sponsor 
notification as required for trials with industry support. Alternate process for expedited AE 
reporting to the AMC protocol chairs and AMC Operations and Data Management Center 
(ODMC) within the clinical data entry system (AdvantageEDC or Advantage eClinical only) may 
be defined in the protocol for select trials (international studies and The ANCHOR Study). 
All serious adverse events (SAEs) received by the AMC ODMC will be reviewed by the AMC 
medical monitor at the AMC ODMC for consideration of individual participant safety, safe trial 
conduct, data reporting quality for AE term selection, and appropriate application of the regulatory 
criteria for seriousness, expectedness, and relatedness to the investigational therapy. If alternate 
procedures are followed for SAE review, the process for adequate medical monitoring will be 
defined in the AMC protocol and the Transfer of Regulatory Obligations (TORO) with the sponsor. 
AMC medical monitor review includes review of the CTEP-AERS report before CTEP submission 
for IDB review (if applicable), or review of the SAE report in the data entry system for trials not 
using CTEP-AERS for expedited reporting. The IND sponsor or its designee will issue the 
determination as to whether the AE requires IND safety reporting to FDA as a serious and 


 
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unexpected suspected adverse drug reaction (SUSAR). For protocols not conducted under an IND, 
in the event of disagreement between the reporting physician and the AMC medical monitor 
regarding the relationship of the AE to the investigational agent(s) (i.e., determination of whether 
the attribution is unrelated or unlikely, or possible, probable, or definite), the AMC medical 
monitor will provide the final determination of the relationship. IND safety reporting to FDA is 
performed by CTEP for trials conducted under a CTEP IND; IND safety reporting is performed 
by the sponsor or sponsor’s designee (AMC ODMC or other party defined in the study agreement 
or TORO) for IND studies sponsored by AMC investigators or industry sponsors. 
Expedited reporting to the Institutional Review Board (IRB) 
The requirements for IRB review will be identified in the protocol section on ethical and regulatory 
obligations. All AMC trials initiated before September 1, 2020 and all international sites for all 
AMC studies are subject to local IRB review; only U.S. sites are subject to the NCI requirement 
to use a single IRB for protocols initiated on or after September 1, 2020. For trials subject to local 
IRB review, the site principal investigator is responsible for ensuring that expedited AE reports 
for its trial participants and any unanticipated problems that affect the local institution only are 
submitted to the local IRB of the reporting institution, per the local IRB’s requirements for such 
reporting. For studies reviewed by the single IRB, the protocol chair will render a determination 
as to whether a SAE or other problem constitutes a trial-wide unanticipated problem that requires 
reporting to that IRB, in accordance with its standards of procedure.  
To comply with investigator notification requirements for IND studies under 21 CFR 312.32 and 
312.55, IND safety reports from all trials the AMC conducts and reports from external sponsors 
investigating the same agents are made available to all investigators upon receipt from the sponsor 
or its designee, either via the password-protected section of the AMC Operations web site (AMC 
trials subject to local IRB review only) or the CTSU website (U.S. trials subject to single IRB 
review/CTEP IND agents). The site clinical investigator responsible for the applicable AMC 
protocol(s) is responsible for reviewing any IND safety reports received and documenting 
submission to the IRB of record (if required by local policy) within the timeline defined by the 
Clinical Trials Monitoring Branch (CTMB) audit guidelines. 
Procedures for monitoring trial progress and pharmacovigilance 
For trials using AdvantageEDC or Advantage eClinical for clinical data entry, the AMC ODMC 
provides on demand tabular listings of all reported AEs and SAEs on a participant level to the 
protocol chair and co-chair(s) for review via the password-protected section of the AMC 
Operations web site, www.AIDScancer.org. For trials using OPEN and Medidata Rave for clinical 
data collection, data listing will be made available using that system. Summary reports of AEs by 
frequency and relationship to the investigational agent(s) are provided to all AMC investigators 
and their staff It is the responsibility of each site to provide trial-specific AE listings to their 
respective IRB, if required by its policies. For blinded studies, the AE and SAE listings are 
reviewed and tabulated without treatment assignment. 
Accrual summaries for each AMC trial are updated nightly on the password-protected section of 
the AMC web site. The progress of each AMC trial is reviewed regularly by the protocol chair and 
also by the appropriate Scientific Working Group (SWG) during scheduled conference calls 
(monthly SWG calls and as required, protocol-specific monitoring conference calls). Summary 
accrual, summary AE, and individual SAE reports are provided to SWG leadership and protocol 
chairs to monitor participant safety during these monthly calls. 


 
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The AMC medical monitor reviews listings of all reported AEs on a quarterly basis for assuring 
compliance with the protocol requirements for AE reporting and the identification of any safety 
concerns (individual AE or increased frequency/severity of expected AEs) for the agents under 
investigation. Findings from these reviews are communicated to the protocol chairs and all AMC 
investigators, and posted to the AMC Operations web site. 
Data and Safety Monitoring Board(DSMB) review 
The AMC has formed an independent Data and Safety Monitoring Board (DSMB) for AMC trials 
and for the ANCHOR Study. As required by NCI policy, the AMC requires DSMB review for all 
phase III randomized trials. All other clinical trials that the AMC initiates will be reviewed by the 
AMC ODMC and AMC Statistical Center during protocol development to issue a recommendation 
as to whether the study requires DSMB oversight, which will require the approval of the AMC 
Executive Committee. This determination will be based on the phase of the study, experimental 
design, risk posed by the investigational approach, extent of data available on the safety of an 
investigational agent, risk posed by the natural course of the health condition under research, and 
the categories of vulnerable populations involved. The involvement of a DSMB in reviewing an 
AMC protocol will be identified in each clinical protocol as approved by CTEP and, as applicable, 
required by the IRB of record. 
Regarding the composition of the AMC DSMB, voting members usually include physicians, 
statisticians, an ethicist, and a patient advocate. All voting members have no other affiliation to 
the AMC and are appointed by the AMC Executive Committee with the approval of the OHAM 
Director. Nonvoting members are the AMC group statistician, the protocol statistician, an AMC 
ODMC staff member, two representatives (normally a clinician or statistician) from CTEP, and 
the grant program directors from the NCI Office of HIV and AIDS Malignancy (OHAM). 
The DSMB reviews all applicable AMC studies in accordance with the National Cancer Institute’s 
Policy for Data and Safety Monitoring. Confidential reports of all trials under review are prepared 
by the AMC group statistician with support from the AMC ODMC. A written report containing 
the current status of each trial monitored, and when appropriate, any toxicity and outcome data, 
are sent to DSMB members by the AMC ODMC within the timelines specified by the DSMB 
charter. This report addresses specific toxicity issues and any other concerns about the conduct of 
the trial, as defined by the protocol plan for DSMB review. The report may contain information 
for the DSMB to render determinations for participant safety, early trial termination, results 
reporting, or continuing accrual or follow-up. 
The results of each DSMB meeting are summarized in a formal report sent by the DSMB chair to 
the AMC group chair and AMC ODMC. The DSMB report contains recommendations on whether 
to close each study reviewed, whether to report the results, and whether to continue accrual or 
follow-up. A primary recommendation (e.g., continue with no change; recommended or required 
modification; stop) must be included in the document. The group chair or designee is then 
responsible for notifying the protocol chair and relevant SWG chair before the recommendations 
of the DSMB are carried out. In the unlikely event that the protocol chair does not concur with the 
DSMB, then the OHAM program directors and the NCI division director or designee must be 
informed of the reason for the disagreement. The protocol chair, relevant SWG chair, group chair, 
DSMB chair, and NCI division director or designee will be responsible for reaching a mutually 
acceptable decision about the study. CTEP approval of a protocol amendment will be required 
prior to any implementation of a change to the study. 


 
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Following a DSMB meeting, the DSMB’s recommendations are provided to all AMC investigators 
and staff. It is each site principal investigator’s responsibility for conveying this information to its 
local IRB as relevant for its protocol participation. For trials reviewed by a single IRB, the AMC 
ODMC will support notification to the IRB as required per its procedures. 
Cohort trial reviews not subject to DSMB review 
For phase I dose escalation trials, dose escalation (or dose de-escalation) is based on the rules in 
the protocol and the protocol chair, AMC medical monitor, and protocol statistician determine 
whether these criteria have been met based on a review of all safety data for the protocol-defined 
evaluation period. If applicable for phase II trials, stopping the trial for toxicity or efficacy, or 
suspending enrollment pending observation of responses in a multi-stage phase II trial, is based on 
meeting criteria stated in the protocol, and the protocol chair, AMC medical monitor, and protocol 
statistician determine whether these criteria have been met. 
Plans for Assuring Compliance with Requirements Regarding AE Reporting 
The protocol chair, AMC group chair, and the AMC ODMC share responsibility in assuring that 
participating investigators comply with applicable regulatory and protocol requirements for AE 
reporting. The AMC site principal investigator certifies compliance with NCI and FDA 
requirements for trial conduct by signing the site subaward agreement for the grant and the AMC 
Adherence Statement for site membership; clinical investigators also certify compliance in 
completing the protocol signature page for each protocol active at the site, and Form FDA-1572 
for CTEP investigator registration, and also for AMC IND studies sponsored by AMC 
investigators or industry sponsors. Protocol compliance with AE identification, assessment and 
reporting requirements is assessed by the AMC ODMC using several methods: 1) programmed 
system checks and messages to instruct the site to complete routine and/or expedited reporting 
when certain criteria are reported in the clinical data entry system; 2) programmed data reports 
provided to the protocol chairs that identify reports requiring expedited AE reporting; 3) remote 
review of data entry or data reports to ensure compliance with protocol and NCI AE reporting 
requirements; 4) AMC medical monitor review described in the section above; and, 5) routine site 
audits by reviewing the site’s source documentation. 
The clinical data entry systems used for AMC studies include the Oncology Patient Enrollment 
Network, OPEN for enrollment, and Medidata Rave for clinical data entry for enrolled 
participants; trials activated before September 1, 2020 or that involve only AMC international sites 
may be reported in AdvantageEDC/Advantage eClinical, a web-based data entry and enrollment 
system. These data entry systems are programmed to notify the site investigator, protocol chair, 
AMC medical monitor, and AMC ODMC via email in the event that a site reports an AE that 
meets expedited reporting criteria to NCI and/or FDA. Additional reporting conditions may be 
programmed depending on the sponsor reporting requirements of a given protocol (e.g., adverse 
events of special interest [AESI]). If the site does not follow with an expedited report, the AMC 
ODMC contacts sites to request compliance with reporting requirements. Additionally, the 
protocol chair, AMC ODMC, and the AMC medical monitor review reported AEs on a routine 
basis to identify AEs reported by sites that require expedited reporting. The protocol chair, AMC 
SWG chairs, AMC group chair, and IND sponsors have general oversight for assuring that routine 
and expedited adverse reporting requirements are met by the responsible parties. 
For studies monitored by CTEP using the Data Mapping Utility (DMU), cumulative protocol- and 
patient-specific data will be submitted weekly to CTEP electronically via the DMU. For trials 


 
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monitored by the NCI’s Clinical Data Update System (CDUS), AE information is transmitted 
electronically to NCI on a quarterly basis. For trials monitored by NCI’s Clinical Trials Monitoring 
Service (CTMS), AE information is transmitted electronically to NCI every two weeks. 
Plans for Assuring that any Action Resulting in a Temporary or Permanent Suspension of 
an NCI-Funded Clinical Trial is Reported to the NCI Grant Program Director Responsible 
for the Grant 
In the event that temporary or permanent suspension of a trial, or major modification to the 
protocol is under consideration, the protocol chair will convene the AMC ODMC, AMC Statistical 
Center, and SWG chair by conference call to discuss the options. Suspension actions will also be 
reviewed by the AMC Executive Committee for program oversight and direct communication of 
the action with the OHAM program directors. For phase III trials, closure decisions are typically 
rendered by the AMC DSMB; if the trial in question is under AMC DSMB oversight but rendered 
by the AMC investigators, the AMC DSMB will be notified of the suspension and the reason. For 
phase I and II trials, the protocol chair also has the option of asking the DSMB to review the study. 
The AMC ODMC will inform the CTEP Protocol Information Office (PIO), with copy to OHAM 
Directors, when studies are temporarily or permanently closed. In the event of major trial 
modification, CTEP must approve all protocol amendments prior to distributing to the AMC sites. 
Plans for Assuring Data Accuracy and Protocol Compliance 
All study data for AMC clinical trials are entered directly by AMC clinical site staff into the 
applicable clinical data entry system for the trial. During data entry, the system performs validation 
checks on many fields and performs consistency checks between select fields. Range checks are 
placed on each field to eliminate entry of out-of-range values. Edit check programs are run on the 
database on a set schedule to identify and resolve inconsistencies between forms or data collected 
at different points in time. Submitted data entry forms are reviewed for compliance with the 
protocol and data entry instructions according to the AMC ODMC’s standards for data quality 
processes. AMC ODMC staff routinely interacts with site staff to resolve any data submission 
problems. 
In accordance with NCI guidelines, the AMC ODMC conducts audits at the AMC sites to evaluate 
compliance with regulatory issues, and to review data for specific cases by checking source 
documents. These reports are sent to the site principal investigator and to the NCI. In the event 
that major violations are identified, sites are asked to provide a written corrective and preventative 
action plan to correct deficiencies. If needed, a repeat site audit is conducted. In the event that a 
site does not correct deficiencies in a pre-determined time frame, the AMC Executive Committee 
has the option to implement remedial action(s) for the site. Possible actions include, but are not 
limited to, suspending enrollment of new patients to AMC trials until deficiencies are corrected; 
recommending a decrease in funding to the site; and requiring specific training for site 
investigators or staff members. 


 
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APPENDIX VII: PARTICIPANT DRUG DIARY 
YOU MUST KEEP THIS DIARY AND BRING IT TO EVERY APPOINTMENT 
 
Instructions for participants: 
Please record the date and time that your nelfinavir dose was taken. Be sure to record the doses 
when you take them and avoid writing entries for several days at once.  
In the “Comments” section write any problems you are having with the medicines or if you missed 
a dose and why or if you only took part of the medicine. 
When you are finished, bring this diary with you when you next see the Doctor or Study Staff. 
Your nelfinavir tablets should be taken with a meal, twice daily (once in the morning and once in 
the evening).  
Nelfinavir should be taken with a moderately high fat meal, for example that includes oil, butter, 
eggs, or meat.  
If you cannot swallow the tablet whole, you may dissolve the tablet in a small amount of water. 
Drink all of the mixture after the table dissolves. Then refill your glass with water and drink all of 
the water right away. Do not mix with acidic foods or juice (apple juice, applesauce, or orange 
juice) because it will make it taste bad. Someone in the clinic will talk to you about the diet 
requirements. 
Missed nelfinavir doses, regardless of reason, SHOULD be made up if it is within 6 hours of the 
missed dose. Do not make up the missed dose if within an hour from the next dose. If you vomit, 
do not take more pills to make up the dose. 
 


 
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AMC-098 Drug Diary 
 
Participant ID #: 098- ___ ___ ___ - ___ ___ ___ ___ ___ 
Day  
Date 
DD/MMM/YYYY 
Time 
Nelfinavir Taken 
(circle AM/PM) 
# of 
Tablets 
Taken 
Time 
Nelfinavir Taken 
(circle AM/PM) 
# of 
Tablets 
Taken 
Comments 
Week #: _________ 
Take ________ tablets twice a day (morning and evening) with a moderately high fat meal. 
1 
___/______/_____ 
___:___ AM PM 
________ 
___:___ AM PM 
________ 
 
2 
___/______/_____ 
___:___ AM PM 
________ 
___:___ AM PM 
________ 
 
3 
___/______/_____ 
___:___ AM PM 
________ 
___:___ AM PM 
________ 
 
4 
___/______/_____ 
___:___ AM PM 
________ 
___:___ AM PM 
________ 
 
5 
___/______/_____ 
___:___ AM PM 
________ 
___:___ AM PM 
________ 
 
6 
___/______/_____ 
___:___ AM PM 
________ 
___:___ AM PM 
________ 
 
7 
___/______/_____ 
___:___ AM PM 
________ 
___:___ AM PM 
________ 
 
Week #: ________ 
Take ________ tablets twice a day (morning and evening) with a moderately high fat meal. 
1 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
2 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
3 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
4 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
5 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
6 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
7 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
8 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
9 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
10 
___/______/_____ 
___:___ AM PM 
_______ 
___:___ AM PM 
________ 
 
Please return the unused tablets to your doctor with your diary at your next appointment. 
FOR STUDY TEAM USE ONLY 


 
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AMC-098 Drug Diary  
 
Participant ID #: 098- ___ ___ ___ - ___ ___ ___ ___ ___ 
 
Number of tablets dispensed 
 
Date returned 
 
Number of tablets returned 
 
Number of days in this cycle (14 days +/- 3 days) 
 
Number of tablets that should have been taken 
 
Number of tablets reported taken 
 
Discrepancy Notes:  
 
 
 
 
 
 
 
 
Staff Signature: ____________________________________ Date: _____________ (DDMMMYYYY) 
NOTE: Non-compliance with study agent administration and/or diary completion should be noted at the 
time of diary collection and the participant should be instructed again regarding dosing instructions. 


 
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APPENDIX VIII: CENTRAL PATHOLOGY REVIEW 
Required Tissues 
Participants must have measurable cutaneous Kaposi sarcoma (KS) that has been pathologically 
confirmed by the local pathologist. Participants must have one of the following for the purposes 
of central pathology review: 
• Diagnostic tissue block or H&E plus five blank FFPE sections for LANA staining , or 
• High quality images of the LANA staining for electronic submission for pathology review and 
H&E is available on site 
Handling of Tissues 
Domestic tissues should be submitted to the following address: 
Sylvia Silver, DA 
George Washington University Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: 202-994-2945 
Fax: 202-994-5056 
International tissues should be submitted to the following address: 
Johann Schneider, MMed Anat Path 
Division of Anatomical Pathology 
National Health Laboratory Service 
10th Floor Green Avenue, Room 52 
Tygerberg Hospital 
Tygerberg 
7535 South Africa 
Phone: 27-21-938-4041 
Fax: 27-21-938-6559 
Email: jws2@sun.ac.za 
Record of Specimens: This study will track specimens via GlobalTraceSM, a component of the 
AMC Advantage eClinical system. The GlobalTraceSM shipment manifest must accompany all 
specimen shipments. 
Pathology Review 
Ethel Cesarman, MD 
Weill Medical College of Cornell University 
Department of Pathology 


 
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APPENDIX IX: SPECIMEN PREPARATION AND SHIPPING INSTRUCTIONS FOR 
NELFINAVIR AND METABOLITE PHARMACOKINETIC STUDIES 
Blood for nelfinavir and metabolite PK assessments will be collected immediately prior to  dose 
administration (- 3 day window) at week 1/cycle 1 through completion of week 15/cycle 9. A 
maximum of nine (9) specimens will be collected. .A window of - 3 days is allowed. The actual 
sample collection times should be recorded on a pharmacokinetic worksheet that also documents 
the time of nelfinavir administration (previous and current dose; along with the use of a 
participant dosing diary (See Appendix VII). 
In addition, when feasible, samples will be requested from the participant at the time of disease 
progression and in the event of DLT or other persistent and severe toxicity. For these optional 
samples, a blood sample should be drawn as close as possible to the time of the event with 
documentation of the last nelfinavir dose administered. 
Collection, Processing and Storage (only 1 tube is necessary for the PK assessment for 
nelfinavir) 
1) Each sample will comprise ~ 6 mL of venous blood drawn into a 6-mL lavender top tube with 
K2-EDTA as the anticoagulant. Immediately after collection, the tube should be gently inverted 
8 to 10 times to mix the anticoagulant with the blood sample. The tube should be stored upright 
on ice until centrifugation; centrifugation and sample processing should be performed within 
30 minutes of sample collection. 
2) The plasma fraction should be separated by placing the collection tube into a refrigerated 
centrifuge (4 to 8°C) in a horizontal rotor (with a swing-out head) for a minimum of 10 minutes 
at 1500 to 1800 relative centrifugal force (RCF). 
3) The plasma fraction will be withdrawn by pipette and divided into 3 polypropylene freezing 
tubes (with each tube receiving approximately equal aliquots and at least 0.5 mL volume). 
4) All sample collection and freezing tubes will be clearly labeled in a fashion that identifies the 
participant, the study period, and the collection date and time. Labels will be fixed to freezing 
tubes in a manner that will prevent the label from becoming detached after freezing. 
5) After processing, samples should be placed into a freezer at approximately –70°C. 
With a black, water resistant, fine-tipped sharpie pen, label each specimen label with the following 
information: 
• 
Protocol #: AMC-098 
• 
11-digit Participant ID # 
• 
Specimen type: “Plasma” 
• 
Specimen purpose: “Pharmacokinetic Analysis” (for the 3 aliquots) 
• 
Date/Time collected: 
*The nominal time point of the blood draw should be written on the specimen label (e.g., day, and 
pre-dose, 1 hour, 2 hours, etc.) In GlobalTraceSM, enter the time collected and be sure to indicate 
the nominal time point in the comments section when adding specimens. 


 
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If there were samples not obtained at the required time points, please inform the Analytical 
Pharmacology Core (APC) Laboratory prior to shipping. 
Shipment 
Samples will be kept at the study site and shipped periodically during the study to the APC 
Laboratory. Unless otherwise stated, samples will be shipped to the APC Laboratory under the 
direction of Michelle A. Rudek, Pharm.D., Ph.D. 
Specimens should be stored through the duration of the PK study (through Week 15) and shipped 
as a batch by participant (more than one participant/shipment is acceptable if the site has > 1 
participant on-study). 
A participant's samples should be shipped to the APC lab within 1 month of the last sample's 
collection date. (i.e., if the Week 15 sample is collected on 1/1/2016, all of that participant's samples 
should be at the APC lab by 2/1/2016). If a second set of participant samples can be batched by 
waiting up to 2 weeks (i.e., 1.5 months). 
Please ship 2 aliquots to the APC laboratory. Once receipt is confirmed, the third/back-up 
aliquot may be shipped (after 2 successful shipments, all 3 aliquots can be shipped at once). 
Overnight shipments should occur on Monday through Wednesday (Tuesday is the preferred day) 
except when the following day is a holiday. A fax or call should be place to the Analytical 
Pharmacology Core Laboratory prior to shipment providing the shipment tracking information. 
Samples should be shipped on dry ice to: 
Analytical Pharmacology Core Laboratory* 
Attn: AMC Nelfinavir Study Samples 
1650 Orleans St. CRB1 Rm 184 
Baltimore, MD 21231-1000 
Phone: 410-502-7192 or 410-955-1129 
Fax: 410-502-0895 
Email: onc-pharmacology@lists.johnshopkins.edu 
Record of Specimens 
This study will track specimens via GlobalTraceSM, a component of the AMC Advantage eClinical 
system. The GlobalTraceSM shipment manifest must accompany all specimen shipments. 


 
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APPENDIX X: AMC BIOREPOSITORY SPECIMEN PREPARATION AND SHIPPING 
INSTRUCTIONS FOR CORRELATIVE STUDIES 
Regimen: Required study specimens are included in Appendix II. All specimens will be banked at 
the domestic or international AMC biorepository, which will serve as a tissue source site for 
processing samples for all AMC sites, for testing at AMC core labs and outside labs. Test will be 
conducted at the end of enrollment for each phase or within one year of acquisition of sample. 
Assays procedures are described in the AMC manual of operation(s) and available from the 
network core laboratories. Assays details may change as technology progresses. 
Assays as proposed in exploratory objectives (Section 2.4): 
• Plasma for herpesvirus (KSHV) and EBV viral load (AMC Virology Core) 
• PBMC for herpesvirus (KSHV) latent virus (AMC Virology Core) 
• PBMC for drug metabolism profile (Genotyping) (AMC Genomics Core) 
• Tissue (skin of KS) biopsies: RNAlater for gene expression profiling (AMC Genomics Core) 
• Tissue (skin of KS) biopsies: formalin for IHC (AMC Pathology Core) 
• Saliva swabs for multiple herpesvirus (KSHV, HSV, EBV, HCMV) (AMC Genomics Core) 
• Nelfinavir PK (AMC Pharmacology Core) (See Appendix IX) 
GENERAL 
A. 
To ship blood specimens, use a diagnostic shipper approved for a volume of at least 30 cc. 
The use of the SAF-T-PAK STP 210 diagnostic cardboard shipper is recommended. These 
shippers may be ordered at the SAF-T-PAK website: www.saftpak.com. The following 
instructions below are for use with the recommended STP-210 shipper. If using another 
federally approved diagnostic shipper, please follow instructions provided for that specific 
shipper. 
NOTE: Specimens MUST BE SHIPPED Sunday through Thursday as an OVERNIGHT 
PRIORITY shipment. Specimens are NOT ACCEPTED ON SATURDAYS OR 
SUNDAYS in the AMC biorepository. 
B. 
INSTRUCTIONS FOR PERIPHERAL BLOOD SPECIMENS FOR PLASMA AND 
PBMCS (FOR RESEARCH) COLLECTED ON SUNDAY – THURSDAY 
From study participant, draw: 
One 8.5 cc (mL) yellow top [acid citrate dextrose (ACD)] tube at two time points: prior to 
initiation of study drug (enrollment visit and prior to first dose, timing not important); and 
at each biweekly study visit while on high dose nelfinavir treatment. 
With a black, water resistant, sharpie pen, label each specimen with the following 
information: 
• AMC Protocol # 098 
• AMC Participant ID# 
• Date and time of collection 


 
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• Specimen type, i.e., WB = Whole Blood 
• Specimen purpose: Research 
Specimen Shipment 
• 
Seal the tops of the tube(s) with Parafilm. 
• 
Place the sealed tube(s) into bubble wrap (provided in STP-210 kit). 
• 
Tape around the bubble wrap so that the roll stays together and the tubes cannot fall 
out or break. 
• 
Place absorbent material sheet around the bubble wrapped tubes and slip into a 
biohazard poly-bag and “self-seal.” 
• 
Place poly-bag containing tubes into the white TYVEK bag and seal. 
• 
Place the TYVEK bag into the STP-210 diagnostic cardboard shipper. Seal the 
cardboard shipper with clear packing/shipping tape. 
• 
Affix the FEDEX air bill on blank side of the shipper making sure that it is marked 
“FEDEX PRIORITY OVERNIGHT.” 
• 
Mark “OTHER” in the air bill under “Packaging.” Please use the FedEx # available on 
the AMC member’s only website. 
• 
Under air bill section “Special Handling” indicate “YES-SHIPPERS DECLARATION 
NOT REQUIRED.” 
• 
Place “From/To” information onto areas provided on the shipper. 
DOMESTIC BLOOD SPECIMENS should be shipped by overnight express at room 
temperature to: 
Sylvia Silver, DA 
AMC Biorepository 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: 202-994-2945 
Fax: 202-994-5056 
Email: ssilver@gwu.edu 
• 
Make certain that shipper is already either pre-labeled with ‘UN#3373’ stamp or make 
a paper label with ‘UN#3373” and affix it to the shipper. 
• 
Make certain that the net volume of the specimen being shipped is written in the space 
provided on the shipper or make a separate label with the volume in mL and affix to 
the shipper. 
• 
Affix air bill to shipper so that the ‘UN’ and ‘VOLUME’ labels are visible. 
• 
RETAIN THE TOP COPY OF THE AIRWAY BILL FOR YOUR RECORDS. 
• 
Place the box in the FedEx pickup area at your site or call to request a package pickup. 


 
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Please Note: The shippers will be mailed back to each AMC site. 
Specimens should be sent by 24-hour shipment at room temperature. If collecting on a 
Friday through Saturday where 24-hour shipment is not possible, please see Section C 
below for instructions regarding separation of Plasma and PBMCs from blood. In this case 
separation will need to occur on site and within 2 hours of blood collection. 
C. 
INSTRUCTIONS FOR SEPARATION OF BLOOD FOR PLASMA AND PBMCS 
(FOR RESEARCH) COLLECTED ON FRIDAY - SATURDAY 
In the event that blood samples are drawn on Friday through Saturday, the samples must 
be processed into plasma and peripheral blood mononuclear cells (PBMC) immediately to 
maintain their viability for analysis. 
From study participant, draw: 
One 8.5 cc (mL) yellow top [acid citrate dextrose (ACD)] tube for PBMCs and plasma (see 
below for PBMC and plasma separation directions) at two time points: prior to study drug 
initiation (enrollment and prior to first drug dose acceptable, exact timing not important); 
and at each biweekly study visit while on nelfinavir treatment. 
With a black, water resistant, sharpie pen, label each specimen with the following 
information: 
• AMC Protocol # 098 
• AMC Participant ID# 
• Date and time of collection 
• Specimen type, i.e., WB = Whole Blood 
• Specimen purpose: Research 
Preparation of plasma and peripheral blood mononuclear cells (PBMCs) 
Blood is to be processed on site within 6 hours of collection. 
Materials 
• Lymphocyte Separation Medium (LSM Solution, Ficoll-Hypaque - sterile) 
• 15 mL conical centrifuge tubes (sterile) 
• PBS (sterile) 
• 1 mL, 5 mL and 10 mL serologic pipettes (sterile) 
• 1.5 mL NUNC tubes 
• Alcohol-saturated, control rate freezer container 
• DMSO freezing media 
• Lonza BioWhittaker TM Cryoprotective Medium (catalog BW12-132A) 
• 50% Heat Inactivated Fetal Bovine Serum 
Plasma separation and freezing procedures 


 
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1. The 10 mL tubes of whole blood in acid citrate dextrose should be rotated gently two 
or three times before being centrifuged. Do not transfer before centrifugation. 
2. Separate the cells by centrifugation at 500 g for 10 minutes. 
3. Remove 0.5 mL aliquots of plasma and put into separate 1.5 mL NUNC tubes and 
transfer to liquid nitrogen storage. 
PBMC separation and freezing procedures 
1. The cells and plasma remaining from the previous step are transferred into a 15 mL 
conical tube or 50 mL centrifuge tube depending on volume. 
2. Sterile PBS should be added to the suspended whole blood cells in an equal volume 
and pipetted up and down to mix (1:1). 
3. The whole blood-PBS mixture should be carefully overlaid onto 4-5 mL of room 
temperature LSM or Ficoll-Hypaque solution in a sterile 15 ml conical centrifuge tube. 
A sharp interface should exist between the LSM and the whole blood mixture. (If the 
layer of LSM gets mixed with the blood-PBS, the tube should be gently rotated to mix 
the blood, PBS, and LSM, and transfer to a 50 mL sterile conical tube. An equal volume 
of PBS is added, and the cells are separated at 600 g for 15 minutes. After removal of 
LSM-PBS supernatant, return to Step 2). 
4. Centrifuge the 15 mL conical tube for 30 minutes at 900 g at room temperature. The 
mononuclear leukocytes (principally lymphocytes and monocytes) will band at 
plasma/LSM interface. 
5. The fluffy white layer just below the plasma layer should be aspirated off and 
transferred to an appropriately labeled 15 mL sterile conical centrifuge tube. Be careful 
to remove only the interface and a minimum amount of the LSM or Ficoll-Hypaque. 
6. Add three volumes of PBS to the cell suspension and or enough to fill conical and mix 
by pipetting up and down. 
7. Centrifuge at 500 g for 10 minutes. 
8. Aspirate off and discard supernatant, taking care not to disturb pellet. 
9. Resuspend in 12 mL of PBS. Take 10 µl of suspension for cell counting (dilute 
accordingly whether using a hemocytometer or automated cell counter). Centrifuge 
again for 10 minutes at 500g to wash cells. 
10. Using a 1 ml pipette, the *DMSO freezing mixture should be added dropwise to the 
cell pellet suspension. Gently finger-tap between drops to resuspend cells. If the cell 
pellet is small, only 0.5 mL of freezing media is added (and only one aliquot of cells is 
frozen). If the cell pellet is large, up to 2 mL of freezing media can be added in a drop 
wise fashion. (Cell densities of 1-10 million PBMC/ml are best for cryopreservation. 
If a hemocytometer is available, the optimal concentration is 5 x 106 PBMC/mL). 
*Important: Do not put the DMSO containing media on the cell button all at once. 
Freeze the cell suspension in 0.5 mL aliquots in sterile NUNC vials by placing the NUNC 
tubes in a room temperature, alcohol saturated, control rate freezer container and store in 


 
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the -80°C freezer overnight. Transfer the cell suspension into the liquid nitrogen 
temperature freezer for long-term storage the next working day. 
GENERAL 
Plasma and PBMC specimens may be shipped in batches monthly. To ship blood 
specimens, use a diagnostic shipper approved for a volume of at least 30 cc. The use of the 
SAF-T-PAK STP 210 diagnostic cardboard shipper is recommended. These shippers may 
be ordered at the SAF-T-PAK website www.saftpak.com. The following instructions 
below are for use with the recommended STP-210 shipper. If using another federally 
approved diagnostic shipper, please follow instructions provided for that specific shipper. 
NOTE: Specimens MUST BE SHIPPED Sundays through Thursday as an OVERNIGHT 
PRIORITY shipment. Specimens are NOT ACCEPTED ON SATURDAYS OR 
SUNDAYS. 
SPECIMEN PREPARATION, PACKAGING, AND SHIPMENT 
Blood specimens 
With a black, water resistant, sharpie pen, label each specimen with the following 
information:  
• AMC Protocol #098 
• AMC Participant ID# 
• Date and time of collection 
• Specimen type: i.e., P = Plasma; PBMCs= Peripheral Blood Mononuclear Cells 
• Specimen purpose: Research 
Specimen shipment 
• 
Seal the tops of the tube(s) with Parafilm. 
• 
Place the sealed tube(s) into bubble wrap (provided in STP-210 kit). 
• 
Tape around the bubble wrap so that the roll stays together and the tubes cannot fall 
out or break. 
• 
Place absorbent material sheet around the bubble wrapped tubes and slip into a 
biohazard poly-bag and “self-seal.” 
• 
Place poly-bag containing tubes into the white TYVEK bag and seal. 
• 
Place the TYVEK bag into the STP-210 diagnostic cardboard shipper. Seal the 
cardboard shipper with clear packing/shipping tape. 
• 
Affix the FEDEX airbill on blank side of the shipper making sure that it is marked 
“FEDEX PRIORITY OVERNIGHT.” 
• 
Mark “OTHER” in the airbill under “Packaging.” Please use the FedEx # available on 
the AMC member’s only website. 
• 
Under airbill section “Special Handling” indicate “YES-SHIPPERS DECLARATION 
NOT REQUIRED.” 


 
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• 
Place “From/To” information onto areas provided on the shipper. 
***PLEASE DOUBLE CHECK PACKAGING OF SHIPPER AND DO NOT DEVIATE 
FROM REQUESTED LABELING. Shipping frozen aliquots requires the use of packaging 
acceptable for dry ice and Class 9 label with weight of dry ice written on package. 
Mail to: 
Sylvia Silver, DA 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Tel: 202-994-2945 
Fax: 202-994-5056 
D. 
PREPARATION OF TISSUE SAMPLES 
From KS study participant, obtain: 
Skin biopsy; formalin-fixed 
Three will be obtained: 1). One at baseline; 2). Another at 2 weeks after beginning standard 
dose NFV; and 3). A third at 2 weeks after beginning high dose NFV. Tissue specimens 
(punch biopsies) must be placed into no more than 5 mL buffered formalin and processed 
locally to FFPE. Please refer to the MOP for processing instructions. 
Skin biopsy; RNAlater 
Three will be obtained: 1). One at baseline; 2). Another at 2 weeks after beginning standard 
dose NFV; and 3). A third at 2 weeks after beginning high dose NFV. Tissue specimens 
(punch biopsies) should be placed into 1 mL RNA later (locally sourced or provided to 
each site by the AMC Biorepository in batches of 20). 
*NOTE: Specimens can only be accepted Monday through Friday. Therefore, specimens 
can only be shipped Sunday-Thursday for delivery the next day. Samples in RNAlater 
are to be shipped on cold packs and FFPE block is to be shipped in ambient temperature. 
TISSUE specimens from U.S. sites should be shipped to: 
Sylvia Silver, DA 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: 202-994-2945 
Fax: 202-994-5056 


 
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TISSUE specimens from international sites should be shipped to: 
Johann Schneider, MMed Anat Path 
Division of Anatomical Pathology 
National Health Laboratory Service 
10th Floor Green Avenue, Room 52 
Tygerberg Hospital 
Tygerberg 
7535 South Africa 
Phone: 27-21-938-4041 
Fax: 27-21-938-6559 
Email: jws2@sun.ac.za 
E. 
ORAL SWAB SAMPLES 
Oral swabs will be self-collected by participants daily for 14 days prior to starting study 
drug (14 baseline swabs) and twice weekly beginning on high dose nelfinavir (14 on-
treatment swabs) for quantification of KSHV, EBV, CMV and HSV by qPCR. Swabs and 
tubes containing buffer will be provided to the sites. 
Swabs: Puritan Swabs, Fisher Scientific Polyester; Plastic shaft; 6 x 1/10 in.; 10 pack 
sterile; 1000/CS Catalog #25-806 1PD. 
Buffer: 5X recipe as follows (500 mL): 
• KCL, ACS Reagent  
Sigma  #P3911-500G  
18.65g 
• Tris-HCl, 1M, pH8 
Sigma #T3038 
 
25 mL 
• EDTA, 0.5M, PH8 
Sigma #3690  
 
125 mL 
• Igepal CA_630 
Sigma #l3021-500mL 
25mL 
With a black, water resistant, sharpie pen, label each tube with the following information: 
• AMC Protocol # 098 
• AMC Participant ID# 
• Date and time of collection 
• Specimen type: Oral swabs 
Participants will be instructed how to collect swabs in the following manner (See Appendix 
XIII): 
• Rub the tip of the swabs over the inside of the both cheeks (buccal mucosa), along the 
upper and lower gum-lines inside and outside of the teeth, around the hard palate and 
across the soft palate; end with the posterior wall as tolerated by the participant. 
• Place the swab into opened buffer tube labeled with the participant’s identification 
number. 
• Break off the long cardboard handle so that the lid can be put on tightly.  
• Complete the swab collection portion of the visit CRF. 


 
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• Place the buffer tubes from one participant in one plastic bag. 
Swabs should be stored and shipped at room temperature. 
SWAB specimens from U.S. sites should be shipped to: 
Sylvia Silver, DA 
George Washington Medical Center 
Ross Hall, Room 118 
2300 I Street, NW 
Washington, DC 20037 
Phone: 202-994-2945 
Fax: 202-994-5056 
SWAB specimens from international sites should be shipped to: 
Johann Schneider, MMed Anat Path 
Division of Anatomical Pathology 
National Health Laboratory Service 
10th Floor Green Avenue, Room 52 
Tygerberg Hospital 
Tygerberg 
7535 South Africa 
Phone: 27-21-938-4041 
Fax: 27-21-938-6559 
Email: jws2@sun.ac.za 
F. 
RECORD OF SPECIMENS 
This study will track specimens via GlobalTraceSM, a component of the AMC Advantage 
eClinical system. The GlobalTraceSM shipment manifest must accompany all specimen 
shipments. 
 


 
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APPENDIX XI: DRUGS KNOWN TO BE METABOLIZED BY SELECTED CYP450 ISOENZYMES 
When drugs classified as “substrates” are co-administered with nelfinavir there is the potential for higher concentrations of the 
“substrate.” When nelfinavir is co-administered with compounds classified as “inhibitors,” increased plasma concentrations of nelfinavir 
is the potential outcome. The co-administration of “inducers” would potentially lower plasma nelfinavir concentrations. See Section 
3.2.5 for exact recommendations relating to administration of agents that interact with the CYP450 system. 
Comprehensive List of Drugs That May Have Potential Interactions 
CYP3A4 Substrates 
Albuterol 
Alfentanil 
Alprazolam 
Amlodipine 
Amprenavir 
Aprepitant 
Aripiprazole 
Atazanavir 
Atorvastatin 
Benzphetamine 
Bisoprolol 
Bortezomib 
Bosentan 
Bromazepam 
Bromocriptine 
Buprenorphine 
Buspirone 
Docetaxel 
Doxepin 
Doxorubicin 
Doxycycline 
Efavirenz 
Eletriptan 
Enalapril 
Eplerenone 
Ergoloid mesylates 
Ergonovine 
Ergotamine 
Erythromycin 
Escitalopram 
Estradiol 
Estrogens, conj., synthetic 
Estrogens, conj., equine 
Estrogens, conj., esterified 
Ketoconazole 
Lansoprazole 
Letrozole 
Levomethadyl acetate hydrochloride 
Levonorgestrel 
Lidocaine 
Losartan 
Lovastatin 
Medroxyprogesterone 
Mefloquine 
Mestranol 
Methadone 
Methylergonovine 
Methysergide 
Miconazole 
Midazolam 
Miglustat 
Quetiapine 
Quinidine 
Rabeprazole 
Repaglinide 
Rifabutin 
Rifampin 
Ritonavir 
Saquinavir 
Sertraline 
Sibutramine 
Sildenafil 
Simvastatin 
Sirolimus 
Sufentanil 
Tacrolimus 
Tamoxifen 
Tamsulosin 


 
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CYP3A4 Substrates 
Busulfan 
Carbamazapine 
Cerivastatin 
Chlordiazepoxide 
Chloroquine 
Chlorpheniramine 
Cisapride 
Citalopram 
Clarithromycin 
Clobazam 
Clonazepam 
Clorazepate 
Cocaine 
Colchicine 
Cyclophosphamide 
Cyclosporine 
Dantrolene 
Dapsone 
Delavirdine 
Diazepam 
Digitoxin 
Dihydroergotamine 
Estrone 
Estropipate 
Ethinyl estradiol 
Ethosuximide 
Etoposide 
Felbamate 
Felodipine 
Fentanyl 
Flurazepam 
Flutamide 
Fosamprenavir 
Fulvestrant 
Gefitinib 
Halofantrine 
Haloperidol 
Ifosfamide 
Imatinib 
Indinavir 
Irinotecan 
Isosorbide dinitrate 
Isosorbide mononitrate 
Isradipine 
Mirtazapine 
Modafinil 
Montelukast 
Moricizine 
Nateglinide 
Nefazodone 
Nelfinavir 
Nevirapine 
Nicardipine 
Nifedipine 
Nimodipine 
Nisoldipine 
Nitrendipine 
Norethindrone 
Norgestrel 
Ondansetron 
Paclitaxel 
Pergolide 
Phencyclidine 
Pimozide 
Pioglitazone 
Primaquine 
Telithromycin 
Teniposide 
Terbinafine 
Tetracycline 
Theophylline 
Tiagabine 
Ticlopidine 
Tolterodine 
Toremifene 
Trazodone 
Triazolam 
Trimipramine 
Troleandomycin 
Vardenafil 
Venlafaxine 
Verapamil 
Vinblastine 
Vincristine 
Vinorelbine 
Zolpidem 
Zonisamide 
Zopiclone 


 
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CYP3A4 Substrates 
Diltiazem 
Disopyramide 
Itraconazole 
Ketamine 
Progesterone 
 
CYP3A4 Inhibitors 
Acetominophen 
Acetazolamide 
Amioderone 
Amlodipine 
Amprenavir 
Anastrozole 
Aprepitant 
Atazanavir 
Atorvastatin 
Azelastine 
Azithromycin 
Betamethasone 
Boceprevir 
Bortezomib 
Bromocriptine 
Caffiene 
Cerivastatin 
Chloramphenicol 
Diclofenac 
Dihydroergotamine Diltiazem 
Disulfiram 
Docetaxel 
Doxorubicin 
Doxycycline 
Drospirenone 
Efavirenz 
Enoxacin 
Entacapone 
Ergotamine 
Erythromycin 
Ethinyl estradiol 
Etoposide 
Felodipine 
Fentanyl 
Fluconazole 
Fluoxetine 
Lopinavir 
Losartan 
Lovastatin 
Mefloquine 
Mestranol 
Methadone 
Methimazole 
Methoxsalen 
Methylprednisolone 
Metronidazole 
Miconazole 
Midazolam 
Mifepristone 
Mirtazapine 
Mitoxantrone 
Modafinil 
Nefazodone 
Nelfinavir 
Prednisolone 
Primaquine  
Progesterone 
Propofol 
Propoxyphene 
Quinidine 
Quinine 
Quinupristin 
Rabeprazole 
Risperidone 
Ritonavir 
Saquinavir 
Selegiline 
Sertraline 
Sildenafil 
Sirolimus 
Sulconazole 
Tacrolimus 


 
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CYP3A4 Inhibitors 
Chlorzoxazone 
Cimetadine 
Ciprofloxacin 
Cisapride 
Clarithromycin 
Clemastine 
Clofazimine 
Clotrimazole 
Clozapine 
Cobicistat 
Cocaine 
Conivaptan 
Cyclophosphamide 
Cyclosporine 
Danazol 
Danoprevir 
Darunavir 
Dasabuvir 
Delavirdine 
Desipramine 
Dexmedetomidine 
Diazepam 
Fluvastatin 
Fluvoxamine 
Fosamprenavir 
Glyburide 
Grapefruit juice 
Haloperidol 
Hydralazine 
Ifosfamide 
Imatinib 
Indinavir 
Irbesartan 
Isoniazid 
Isradapine 
Itraconazole 
Ketoconazole 
Lansoprazole 
Lidocaine 
Lomustine 
Nevirapine 
Nicardipine 
Nifedipine 
Nisoldipine 
Nitrendipine 
Nizatidine 
Norfloxacin 
Olanzapine 
Ombitasvir 
Omeprazole 
Orphenadrine 
Oxybutynin 
Paritaprevir 
Paroxetine 
Pentamidine 
Pergolide 
Phencyclidine 
Pilocarpine 
Pimozide 
Posaconazole 
Pravastatin 
Tamoxifen  
Telaprevir 
Telithromycin 
Teniposide 
Testosterone 
Tetracycline 
Ticlopidine 
Tranylcypromine 
Trazodone 
Troleandomycin 
Valproic acid 
Venlafaxine 
Verapimil 
Vinblastine 
Vincristine 
Vinorelbine 
Voriconazole 
Zafirlukast 
Ziprasidone 


 
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CYP3A4 Inducers 
Aminoglutethimide 
Carbamazapine 
Cortisone (high dose) 
Dexamethasone (high dose) 
Efavirenz 
Fosphenytoin 
Hydrocortisone (high dose) 
Methylprednisolone (high dose) 
Modafinil 
Nevirapine 
Oxcarbazepine 
Pentobarbital 
Phenobarbital  
Phenytoin 
Prednisone (high dose) 
Primidone 
Rifabutin 
Rifampin 
Rifapentine 
St. John’s wort 
 
CYP2C19 Substrates 
Amitriptyline 
Celecoxib 
Diclofenac1 
Fluoxetine 
Fluvastatin 
Glibenclamide 
Glimepiride 
Glipizide 
Glyburide 
Ibuprofen 
Irbesartan 
Lornoxicam 
Losartan 
Meloxicam 
S-naproxen→Norpiroxicam 
Nateglinide 
Phenytoin-4-OH2 
Rosiglitazone 
Suprofen 
Tamoxifen 
Tolbutamide1 
Torsemide 
Valproic acid 
S-warfarin1 
Zafirlukast 
 
CYP2C19 Inhibitors 
Amiodarone 
Efavirenz 
Fenofibrate 
Fluconazole 
Fluvastatin 
Fluvoxamine2 
Isoniazid 
Lovastatin 
Metronidazole 
Paroxetine 
Phenylbutazone 
Probenicid  
Sertraline 
Sulfaphenazole1 
Teniposide 
Voriconazole 
Zafirlukast 


 
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CYP2C19 Inducers 
Carbamazepine 
Enzalutamide 
Nevirapine 
Phenobarbital 
Rifampin 
Secobarbital 
St. John's Wort 
 
Adapted from Cytochrome P-450 Enzymes and Drug metabolism. In: Lacy CF, Armstrong LL, Goldman MP, Lance LL eds. Drug 
Information Handbook 12TH ed. Hudson, OH; LexiComp Inc. 2004: 1619-1631. 
(1). Malhorta et al. (2000). Clin Pharmacol Ther. 69:14-23 
(2). Mathijssen et al. (2002). J Natl Cancer Inst. 94:1247-1249 
(3). Frye et al. (2004). Clin Pharmacol Ther. 76:323-329 
 
Additional information for drug interactions with cytochrome P450 isoenzymes can be found at http://medicine.iupui.edu/flockhart/. 
 


 
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APPENDIX XII: DRUGS KNOWN OR SUSPECTED TO INHIBIT KSHV 
REPLICATION 
 
Direct Acting Antivirals 
acyclovir 
adefovir 
cidofovir 
foscarnet 
ganciclovir 
valacyclovir 
valganciclovir 
 
HIV Protease Inhibitors 
atazanivir 
darunivir 
fosempranavir 
lopinavir 
ritonavir 
tipranavir 
 


 
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APPENDIX XIII: PARTICIPANT INSTRUCTIONS FOR ORAL SWABS 
YOU MUST KEEP THIS DIARY AND BRING IT TO YOUR APPOINTMENT 
Study Participant ID #: _______________ 
You will collect one oral swab on 14 separate days before you start nelfinavir (14 swabs total). 
If you begin taking a higher dose of nelfinavir, you will collect more oral swabs after one week of 
taking the higher dose. You will collect two oral swabs every week for seven weeks (14 swabs 
total). 
How to collect the oral swabs 
1) Collect the oral swabs in the morning before brushing your teeth or eating. 
If you not able to collect the swab in the morning, wait one hour after eating, drinking, or 
brushing your teeth to collect the oral swabs. 
2) Rub the tip of the swab over each of these areas in your mouth as shown below: 
A. The inside of the both cheeks 
B. Along the upper and lower gum-lines inside and outside of the teeth 
C. Around the hard palate and across the soft palate 
D. End with the posterior wall (if you are able) 
 
 
 
B. 
Upper and 
Lower Gums, 
Inside and 
Outside Teeth 
D. 
Posterior 
wall 


 
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Study Participant ID #: _______________ 
 
3) Place the swab into an opened tube. 
4) Break off the long cardboard handle so that the lid can be put on 
tightly. 
5) Place the tubes into the plastic bag and keep the swabs at room 
temperature to bring to your next study visit. 
Please record in the diary below the date that oral swab was done. 
Be sure to record the swabs when you do them and avoid writing entries for several days at once. 
When you are finished, bring this diary with you to your next study visit. In the “Comments” 
section write any problems you are having collecting the swabs or if you missed a swab. 
 
Oral Swab Collection Before Starting Nelfinavir 
Day of Collection 
Date 
MM/DD/YYYY 
Time 
Swab Collected 
(circle AM/PM) 
Comments 
1 
___/___/______ 
___:___ AM PM 
 
2 
___/___/______ 
___:___ AM PM 
 
3 
___/___/______ 
___:___ AM PM 
 
4 
___/___/______ 
___:___ AM PM 
 
5 
___/___/______ 
___:___ AM PM 
 
6 
___/___/______ 
___:___ AM PM 
 
7 
___/___/______ 
___:___ AM PM 
 
8 
___/___/______ 
___:___ AM PM 
 
9 
___/___/______ 
___:___ AM PM 
 
10 
___/___/______ 
___:___ AM PM 
 
11 
___/___/______ 
___:___ AM PM 
 
12 
___/___/______ 
___:___ AM PM 
 
13 
___/___/______ 
___:___ AM PM 
 
14 
___/___/______ 
___:___ AM PM 
 
Please return the swabs to your doctor with your diary at your next study visit. 


 
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Study Participant ID #: _______________ 
 
Please record in the diary below the date that oral swab was done. Be sure to record the swabs 
when you do them and avoid writing entries for several days at once. When you are finished, bring 
this diary with you to your next study visit. In the “Comments” section write any problems you 
are having collecting the swabs or if you missed a swab. 
 
Oral Swab Collection on High Dose Nelfinavir 
Weeks 
Swabs 
Date 
MM/DD/YYYY 
Time 
Swab Collected 
(circle AM/PM) 
Comments 
Week 1 
No Swabs 
Week 2 
Swab 1 
___/___/______ 
___:___ AM PM 
 
Swab 2 
___/___/______ 
___:___ AM PM 
 
Week 3 
Swab 1 
___/___/______ 
___:___ AM PM 
 
Swab 2 
___/___/______ 
___:___ AM PM 
 
Week 4 
Swab 1 
___/___/______ 
___:___ AM PM 
 
Swab 2 
___/___/______ 
___:___ AM PM 
 
Week 5 
Swab 1 
___/___/______ 
___:___ AM PM 
 
Swab 2 
___/___/______ 
___:___ AM PM 
 
Week 6 
Swab 1 
___/___/______ 
___:___ AM PM 
 
Swab 2 
___/___/______ 
___:___ AM PM 
 
Week 7 
Swab 1 
___/___/______ 
___:___ AM PM 
 
Swab 2 
___/___/______ 
___:___ AM PM 
 
Week 8 
Swab 1 
___/___/______ 
___:___ AM PM 
 
Swab 2 
___/___/______ 
___:___ AM PM 
 
Please return the swabs to your doctor with your diary at your next study visit. 


 
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APPENDIX XIV: PARTICIPANT DRUG INFORMATION HANDOUT AND WALLET 
CARD 
Information for Participants, Their Caregivers and Non-Study Healthcare Team on Possible 
Interactions with Other Drugs and Herbal Supplements 
The participant ___________________ is enrolled on a clinical trial using the experimental study 
drug, nelfinavir. This clinical trial is sponsored by the National Cancer Institute. This form is 
addressed to the patient, but includes important information for others who care for this patient. 
These are the things that you as a healthcare provider need to know: 
Nelfinavir interacts with certain specific enzymes in your liver* and may affect the heart’s 
electrical activity (QTc prolongation)**. 
* The enzyme(s) in question is/are CYP3A and CYP2C19. Nelfinavir is broken down by 
this enzyme and may be affected by other drugs that inhibit or induce this enzyme. 
** The heart’s electrical activity may be affected by nelfinavir. The study doctor may be 
concerned about QTc prolongation and any other medicine that is associated with greater 
risk for having QTc prolongation. 
To the participant: Take this paper with you to your medical appointments and keep the 
attached information card in your wallet. 
Nelfinavir may interact with other drugs which can cause side effects. For this reason, it is very 
important to tell your study doctors of any medicines you are taking before you enroll onto this 
clinical trial. It is also very important to tell your doctors if you stop taking any regular medicines, 
or if you start taking a new medicine while you take part in this study. When you talk about your 
current medications with your doctors, include medicine you buy without a prescription (over-the-
counter remedy), or any herbal supplements such as St. John’s Wort. It is helpful to bring your 
medication bottles or an updated medication list with you. 
Many health care providers can write prescriptions. You must tell all of your health care providers 
(doctors, physician assistants, nurse practitioners, pharmacists) you are taking part in a clinical 
trial. 
These are the things that you and they need to know: 
Nelfinavir must be used very carefully with other medicines that use certain liver enzymes or that 
may affect your heart’s electrical activity. Before you enroll onto the clinical trial, your study 
doctor will work with your regular health care providers to review any medicines and herbal 
supplements that are considered strong inducers/inhibitors or substrates of CYP3A or CYP2C19, 
or any medicine associated with greater risk for having QTc prolongation. 
• Please be very careful! Over-the-counter drugs (including herbal supplements) may contain 
ingredients that could interact with your study drug. Speak to your doctors or pharmacist to 
determine if there could be any side effects. 
• Your regular health care provider should check a frequently updated medical reference or call 
your study doctor before prescribing any new medicine or discontinuing any medicine. 
• Your study doctor’s name is ________________________ and he or she can be contacted at 
_____________________________________. 


 
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STUDY DRUG INFORMATION WALLET CARD 
You are enrolled on a clinical trial using the experimental study drug 
nelfinavir. This clinical trial is sponsored by the NCI. Nelfinavir 
may interact with drugs that are processed by your liver, or affects 
the electrical activity of your heart. Because of this, it is very 
important to: 
 Tell your doctors if you stop taking any medicines or if you 
start taking any new medicines. 
 Tell all of your health care providers (doctors, physician 
assistants, nurse practitioners, or pharmacists) that you are taking 
part in a clinical trial. 
 Check with your doctor or pharmacist whenever you need to 
use an over-the-counter medicine or herbal supplement. 
Nelfinavir interacts with a specific liver enzymes called 
CYP3A and CYP2C19, heart’s electrical activity (QTc 
prolongation), and must be used very carefully with other 
medicines that interact with Nelfinavir. 
 Before you enroll onto the clinical trial, your study doctor 
will work with your regular health care providers to review 
any medicines and herbal supplements that are considered 
“strong inducers/inhibitors or substrates of CYP3A and 
CYP2C19, or affect the heart’s electrical activity.” 
 Before prescribing new medicines, your regular health care 
providers should go to a frequently-updated medical 
reference for a list of drugs to avoid, or contact your study 
doctor. 
 Your study doctor’s name is _____________________ and 
can be contacted at _________________________________. 


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SUMMARY OF CHANGES 
A Pilot Study of Nelfinavir for the Treatment of Kaposi Sarcoma 
Version 4.0 
 
NCI Protocol #: AMC-098 
Local Protocol #: AMC-098 
 
NCI Version Date: 08DEC2020 
Protocol Date: 08DEC2020 
 
I. 
Scientific and Substantive Changes 
# 
Section 
Comments 
1. 
WHAT EXTRA 
TESTS AND 
PROCEDURES 
WILL I HAVE IF 
I TAKE PART IN 
THIS STUDY? 
Added statements communicating that if previously submitted 
baseline tissue samples are inadequate to perform IHC studies, 
additional slides from the diagnostic punch biopsy may be requested 
to perform such studies. See protocol summary of changes item 3 
regarding this change. 
II. 
Administrative and Editorial Changes: 
# 
Section 
Comments 
2. 
Global 
Version number and version date were updated from v3.0 dated 
13FEB2019 to v4.0 dated 08DEC2020 
3. 
HOW LONG 
WILL I BE IN 
THIS STUDY? 
Participants will be followed for 8 weeks after discontinuing 
nelfinavir unless in the opinion of the treating physician, the 
participant should start an alternative therapy sooner for treatment of 
KS. Instructions were added requiring follow-up evaluations to be 
completed before participants start a new therapy to treat KS. 
4. 
WHERE CAN I 
GET MORE 
INFORMATION? 
Dr. Gantt’s (Protocol Chair) address and contact information have 
been updated. 


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AMC-098 MODEL INFORMED CONSENT FORM 
Study Title for Study Participants: A Study of Nelfinavir for Treating Kaposi Sarcoma 
Official Study Title for Internet Search on http://www.ClinicalTrials.gov: A Pilot Study of 
Nelfinavir for the Treatment of Kaposi Sarcoma 
A Clinical Trial of the AIDS Malignancy Consortium (AMC) 
WHAT IS THE USUAL APPROACH TO MY CANCER? 
People with Kaposi sarcoma who are not in this study are usually treated with intravenous 
chemotherapy (cancer fighting drugs given through a needle in a vein), cryotherapy (freezing of 
the cancer), radiation, or other treatments depending on how severe the disease is. Sometimes 
combinations or sequences of these treatments are used, and your doctor can explain which may 
be best for you. These treatments can reduce symptoms and may stop the tumor from growing for 
several months or more. 
WHAT ARE MY OTHER CHOICES IF I DO NOT TAKE PART IN THIS STUDY? 
If you decide not to take part in this study, you have other choices. For example: 
• you may choose to have the usual approach described above 
• you may choose to take part in a different study, if one is available, or 
• you may choose not to be treated for cancer 
WHY IS THIS STUDY BEING DONE? 
You are being asked to participate in this study because you are an adult with Kaposi sarcoma that 
has not been improving. The purpose of this study is to test the good and bad effects of the medicine 
called nelfinavir. Nelfinavir could shrink or cure your cancer, but it could also cause side effects. 
Nelfinavir is FDA approved to treat HIV, but it has not yet been tested or FDA approved to treat 
people who already have Kaposi sarcoma. Nelfinavir has also been shown to kill the Kaposi 
sarcoma-associated herpes virus (KSHV) that causes Kaposi sarcoma, and has been found to be 
safe when used at higher doses to treat people with other cancers. 
We will test whether regular or higher doses of nelfinavir help shrink your Kaposi sarcoma or 
cause any side effects. Another purpose of this study is for researchers to learn how well nelfinavir 
blocks the KSHV virus in people taking the study medicine. There will be about 36 people taking 
part in this study. 
WHAT ARE THE STUDY GROUPS? 
All people in the study will get the same study treatment with nelfinavir in the form of pills. Some 
of the people in the study will have HIV and some will not have HIV. If you join the study, you 
will first get the regular approved dose of nelfinavir (1250 mg by mouth twice daily). If the regular 
dose of nelfinavir does not cause your Kaposi sarcoma to shrink enough then you will be given a 
higher dose of nelfinavir (3125 mg by mouth twice daily). If nelfinavir causes bad side effects, the 
dose might be lowered or stopped. 
Nelfinavir should be taken with a moderately high fat meal, for example that includes oil, butter, 
eggs, or meat. If you cannot swallow the tablet whole, you may dissolve the tablet in a small 
amount of water. Drink all of the mixture after the tablet dissolves. Then refill your glass with 


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water and drink all of the water right away. Do not mix with acidic food or juice (apple juice, 
applesauce, or orange juice) because it will make it taste bad. Someone in the clinic will talk with 
you about the diet requirements. If you vomit after taking nelfinavir, do not take more pills to make 
up the dose. 
HOW LONG WILL I BE IN THIS STUDY? 
You will be given the regular dose of nelfinavir for up to 8 weeks. After that, you may be given 
the higher dose of nelfinavir for up to an additional 16 weeks. You may be on nelfinavir for less 
time if you are not having good effects from it or if your cancer gets bigger, or if your cancer goes 
away. After you finish the medicine, your doctor will continue to watch you for bad effects and 
follow your Kaposi sarcoma for up to 8 more weeks. You may be followed for less than 8 weeks 
if your doctor thinks you should start a new therapy sooner. If you start a new therapy to treat your 
KS you will no longer be followed as part of this study. You will be in this study for up to 32 
weeks, during which time you will track your doses of nelfinavir in a drug diary. 
WHAT EXTRA TESTS AND PROCEDURES WILL I HAVE IF I TAKE PART IN THIS 
STUDY? 
Most of the tests that you will have done are part of the usual way people with Kaposi sarcoma are 
treated. However, there are some extra tests and exams that you will need to do if you join in this 
study. 
Before the study: 
• You will need to take a HIV test unless you have had one recently or your usual doctor knows 
for sure that you do have or do not have HIV. 
• If your Kaposi sarcoma was diagnosed without a biopsy (small piece of the Kaposi sarcoma 
removed by surgery) we will ask your doctor to take a biopsy to make sure that you have 
Kaposi sarcoma. 
• We will ask questions related to the risk of getting HIV, including drug use and sexual 
behavior. 
• You will have an electrocardiogram (EKG) within 4 weeks of starting the study 
• You will have a chest X-ray within 4 weeks of starting the study 
• If you are a female who may become pregnant, you will have a pregnancy test 
During the study: 
• You will come to the study clinic every 2 weeks. 
• You will have a nutrition assessment in addition to routine physical examinations. 
• You will have an EKG two weeks after starting standard dose nelfinavir and two weeks after 
starting high dose nelfinavir. 
• You may receive chest X-rays while on treatment if the doctor thinks you need them. 
• If you are a female who may become pregnant you will have a pregnancy test prior to starting 
standard dose nelfinavir and again prior to starting high dose nelfinavir 
• Two Kaposi sarcoma biopsies will be taken before you start nelfinavir, during the regular dose 


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treatment, and during the higher dose treatment. You will have a total of 6 biopsies. These 
samples are required in order for you to take part in this study because the research on the 
sample is an important part of the study. We will use the biopsies to see how nelfinavir works 
on Kaposi sarcoma and the KSHV virus that causes Kaposi sarcoma. The biopsy for the study 
is done in a similar way to biopsies done for cancer diagnosis. Local anesthesia will be used 
for your comfort. If the tissue from the biopsy is not adequate, the study doctors may need to 
use some additional the tissue left over from your biopsy when you were diagnosed with cancer 
to perform these tests. 
• The biopsies will be very small (only a few millimeters across). Adverse effects from these 
biopsies are very uncommon and include mild pain, bruising, bleeding and low risk of 
infection. 
• We will ask you to collect saliva with a swab in your mouth daily for 14 days before you start 
the nelfinavir treatment. During treatment we will ask you to collect saliva with a swab twice 
a week for 7 weeks, during weeks 10-16 of the study. We will use these swabs to see how the 
nelfinavir works against the KSHV virus that causes Kaposi sarcoma. This virus is found in 
the saliva of many people with Kaposi sarcoma. Collecting these swabs is painless. 
• Before you start nelfinavir, we will draw blood samples (about 2 tablespoons total) at separate 
screening visits for research tests. While you are taking nelfinavir, we will draw about 1 
tablespoon of blood every two weeks for research tests. These tests will monitor the good and 
bad effects of nelfinavir. These tests also measure how nelfinavir works against the KSHV 
virus that causes Kaposi sarcoma. We will also use these samples to test for other viruses that 
occur with HIV infection and Kaposi sarcoma. 
Neither you nor your health care plan/insurance carrier will be billed for the collection of the 
biopsies, saliva swabs, or any blood tests that are not part of usual care for Kaposi sarcoma. Results 
from these tests will not be shared with you or your study doctor. 
WHAT POSSIBLE RISKS CAN I EXPECT FROM TAKING PART IN THIS STUDY? 
If you choose to take part in this study, there is a risk that: 
• You may lose time at work or home and spend more time in the hospital or doctor’s office than 
usual. 
• You may be asked sensitive or private questions which you normally do not discuss. 
If you are taking certain medicines, you may not be able to take part in the study. 
If you have HIV, you will continue taking your regular HIV medications throughout the course of 
the study. If you are on certain HIV medications, you may need to change regimens for safety with 
the nelfinavir during the time you are in the study and for a short time after. If you choose not to 
switch to one of the allowed regimens, you may not be able to take part in the study.  
If you take part in the study, you will be given a Participant Drug Information and Wallet Card 
that has information about drugs may interact with nelfinavir which can cause side effects. 
It is possible that your Kaposi sarcoma could get worse while taking nelfinavir. Nelfinavir may 
affect how different parts of your body work such as your liver, kidneys, heart, and blood. The 
study doctor will be testing your blood and will let you know if changes occur that may affect your 
health. 


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There is also a risk that you could have other side effects from nelfinavir or the tests that will be 
done. 
Here are important points about side effects: 
• The study doctors do not know who will or will not have side effects. 
• Some side effects may go away soon; some may last a long time. 
• Some side effects may be serious and may even result in death. 
Here are important points about how you and the study doctor can make side effects less of a 
problem: 
• Tell the study doctor if you notice or feel anything different so they can see if you are having 
a side effect. 
• The study doctor may be able to treat some side effects. 
• The study doctor may adjust nelfinavir to try to reduce side effects. 
The tables below show the most common and the most serious side effects that researchers know 
about. There might be other side effects that researchers do not yet know about. If important new 
side effects are found, the study doctor will discuss these with you. 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving nelfinavir, more than 20 and up to 50 may have: 
• Diarrhea 
• Low red blood cell count (anemia) 
• Low white cell blood cell count 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving nelfinavir, from 2 to 20 may have: 
• Fatigue 
• Dehydration 
• Heartburn 
• Nausea  
• Bloating or gas 
• Rash 
• Low platelets  
• Increase in cholesterol and triglycerides 
• High blood sugar or diabetes 
 
RARE, AND SERIOUS 
In 100 people receiving nelfinavir, 3 or fewer may have: 
• Infection, especially when white blood cell count is low 
• Electrical changes in the heart causing abnormal or dangerous heart rhythm 
Let your study doctor know of any questions you have about possible side effects. You can ask the 
study doctor questions about side effects at any time. 


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Reproductive risks: Reproductive risks have not been seen with nelfinavir. However, higher doses 
of nelfinavir have not been studied in pregnant or breastfeeding women. You should not get 
pregnant or breastfeed a baby while in this study. Check with the study doctor about what types of 
birth control, or pregnancy prevention, to use while in this study. If you are a woman who could 
become pregnant and are taking hormonal birth control, talk to the study doctor. Nelfinavir can 
cause hormonal birth control to fail, and may lead to unplanned pregnancy. To take part in this 
study, you will need to agree to use other non-hormonal birth control methods like condoms or 
abstinence while taking nelfinavir. 
WHAT POSSIBLE BENEFITS CAN I EXPECT FROM TAKING PART IN THIS STUDY? 
It is not possible to know at this time if nelfinavir is better than the usual ways Kaposi sarcoma is 
treated, so this study may or may not help treat your Kaposi sarcoma. This study will help 
researchers learn things that will help people in the future. 
CAN I STOP TAKING PART IN THIS STUDY? 
Yes. You can decide to stop at any time. If you decide to stop for any reason, it is important to let 
the study doctor know as soon as possible so you can stop safely. If you stop, you can decide 
whether or not to let the study doctor continue to provide your medical information to the 
organization running the study. 
The study doctor will tell you about new information or changes in the study that may affect your 
health or your willingness to continue in the study. 
The study doctor may take you out of the study: 
• If your health changes and the study is no longer in your best interest, 
• If new information becomes available, 
• If you do not follow the study rules, 
• If the study is stopped by the sponsor, IRB, or (insert as appropriate: FDA/National Drug 
Authority of Uganda). 
WHAT ARE MY RIGHTS IN THIS STUDY? 
Taking part in this study is your choice. No matter what decision you make, and even if your 
decision changes, there will be no penalty to you. You will not lose medical care or any legal 
rights. 
For questions about your rights while in this study, call the ________________________ (insert 
name of center) Institutional Review Board at __________________ (insert telephone number). 
(Note to Local Investigator: Contact information for patient representatives or other individuals 
at a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can also be listed here.) 
WHAT ARE THE COSTS OF TAKING PART IN THIS STUDY? 
Nelfinavir will be supplied to you at no charge by Pfizer, Inc. while you take part in this study. It 
is possible that the nelfinavir may not continue to be supplied while you are on the study. Although 
not likely, if this occurs, your study doctor will talk to you about your options. 
You and/or your health plan/insurance company will not be billed for the tumor biopsies, saliva 


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swabs, or extra research blood tests that are not part of usual cancer care. 
You and/or your health plan/insurance company will need to pay for all of the other costs of 
treating your cancer while in this study, including the cost of usual tests, procedures, or medicines 
to manage any side effects, unless you are told that certain tests are supplied at no charge. Before 
you decide to be in the study, you should check with your health plan or insurance company to 
find out exactly what they will pay for. 
You will receive $(insert amount) for each study visit you attend. (Note to Local Investigator: 
retain this information and insert amount as applicable in the local consent. If your site will not 
be compensating the participant, please use the following language instead: There will not be any 
monetary compensation for participation in this study.) 
WHAT HAPPENS IF I AM INJURED OR HURT BECAUSE I TOOK PART IN THIS 
STUDY? 
If you are injured or hurt as a result of taking part in this study and need medical treatment, please 
tell your study doctor. The AIDS Malignancy Consortium will not offer to pay for medical 
treatment for injury. (Note to SSA site: add appropriate language for coverage of research-related 
injury costs). Your insurance company may not be willing to pay for study-related injury. If you 
feel this injury was a result of medical error, you keep all your legal rights to receive payment for 
this even though you are in a study. 
WHO WILL SEE MY MEDICAL INFORMATION? 
Your privacy is very important to us and the researchers will make every effort to protect it. Your 
information may be given out if required by law. For example, certain states require doctors to 
report to health boards if they find a disease like tuberculosis. However, the researchers will do 
their best to make sure that any information that is released will not identify you. Some of your 
health information, and/or information about your specimen, from this study will be kept in a 
central database for research. Your name or contact information will not be put in the database. 
There are organizations that may inspect your records. These organizations are required to make 
sure your information is kept private, unless required by law to provide information. Some of these 
organizations are: 
• The sponsor, the AIDS Malignancy Consortium (AMC) 
• The drug company supporting the study, Pfizer Inc. 
• The Institutional Review Board (IRB) is a group of people who review the research with the 
goal of protecting the people who take part in the study. 
• The Food and Drug Administration (FDA) and the National Cancer Institute (NCI) in the U.S., 
(international sites: insert name of national and/or local regulatory authorities who will 
review study records) 
WHERE CAN I GET MORE INFORMATION? 
You may visit the NCI Web site at http://cancer.gov/ for more information about studies or general 
information about cancer. You may also call the NCI Cancer Information Service to get the same 
information at: 1-800-4-CANCER (1-800-422-6237). 
 


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A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
WHO CAN ANSWER MY QUESTIONS ABOUT THIS STUDY? 
You can talk to the study doctor about any questions or concerns you have about this study or to 
report side effects or injuries. Contact the study doctor __________________ (insert name of study 
doctor[s]) at __________________ (insert telephone number). 
You can also contact the Principal Investigator or Protocol Co-Chairs for the AIDS Malignancy 
Consortium: 
Dr. Soren Gantt 
Centre de recherche du CHU Sainte-Just 
3175 Côte Sainte-Catherine 
Montréal Qc H3T 1C5, Canada  
Tel: (604) 875-2151 
Email: soren.gantt.hsj@ssss.gouv.qc.ca 
 
Dr. Rachel Bender Ignacio 
Child & Family Research Institute 
1100 Fairview Ave N, Mailstop E2-112 
Seattle, WA 98109 
Tel: (206) 667-4628 
Email: rbenderi@fredhutch.org 
 
Dr. Richard Ambinder 
Room 389, Cancer Research Building 
1650 Orleans Street 
Baltimore, MD 21287 
Tel: (410)-955-8839 
Email: Rambind1@jhmu.edu 
 
 
OPTIONAL 
SAMPLE 
COLLECTIONS 
FOR 
LABORATORY 
STUDIES 
AND 
DONATION OF LEFTOVER TISSUE SAMPLES TO THE AIDS AND CANCER 
SPECIMEN RESOURCE (ACSR) 
This section is about optional studies you can choose to take part in 
Researchers are trying to learn more about cancer, HIV/AIDS, and other health problems. Much 
of this research is done using samples from your tissue, blood, urine, or other fluids. Through these 
studies, researchers hope to find new ways to prevent, detect, treat, or cure health problems. Some 
of these studies may be about genes. Genes carry information about features that are found in you 
and in people who are related to you. Researchers are interested in the way that genes affect how 
your body responds to treatment. 
If you choose to take part in this study, the study doctor for the main study would like to collect 
unused blood and biopsy tissue left over after the study is done. The researchers ask your 
permission to store and use your samples and related health information (for example, your 
response to cancer treatment, results of study tests and medicines you are given) for medical 
research. The research that may be done is unknown at this time. Storing samples for future studies 
is called “biobanking.” The Biobank is being run by the AIDS and Cancer Specimen Resource 
and is supported by the National Cancer Institute. 
What is involved? 
If you agree to take part, here is what will happen next: 


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1) Your sample and some related health information will be stored in the ACSR Biobank, along 
with samples and information from other people who take part. The samples will be kept until 
they are used up. Information from your medical record may be updated after the study is over. 
2) Qualified researchers can submit a request to use the materials stored in the ACSR. A science 
committee at the ACSR will review each request. There will also be an ethics review to ensure 
that the request is necessary and proper. Researchers will not be given your name or any other 
information that could directly identify you. 
3) Neither you nor your study doctor will be notified when research will be conducted or given 
reports or other information about any research that is done using your samples.  
4) Some of your genetic and health information may be placed in central databases that may be 
public, along with information from many other people. Information that could directly 
identify you will not be included. 
What are the possible risks? 
1) There is a risk that someone could get access to the personal information in your medical 
records or other information researchers have stored about you. 
2) There is a risk that someone could trace the information in a central database back to you. Even 
without your name or other identifiers, your genetic information is unique to you. The 
researchers believe the chance that someone will identify you is very small, but the risk may 
change in the future as people come up with new ways of tracing information. 
3) In some cases, this information could be used to make it harder for you to get or keep a job or 
insurance. There are laws against the misuse of genetic information, but they may not give full 
protection. There can also be a risk in knowing genetic information. New health information 
about inherited traits that might affect you or your blood relatives could be found during a 
study. The researchers believe the chance these things will happen is very small, but cannot 
promise that they will not occur. 
How will information about me be kept private? 
Your privacy is very important to the researchers and they will make every effort to protect it. 
Here are just a few of the steps they will take: 
1) When your sample(s) is sent to the researchers, no information identifying you (such as your 
name) will be sent. Samples will be identified by a unique code only. 
2) The list that links the unique code to your name will be kept separate from your sample and 
health information. The ACSR and AMC staff with access to the list must sign an agreement 
to keep your identity confidential. 
3) Researchers to whom the ACSR and the AMC send your sample and information will not know 
who you are. They must also sign an agreement that they will not try to find out who you are. 
4) Information that identifies you will not be given to anyone, unless required by law. 
5) If research results are published, your name and other personal information will not be used. 
What are the possible benefits? 
You will not benefit from taking part. The researchers, using the samples from you and others, 
might make discoveries that could help people in the future. 


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Are there any costs or payments? 
There are no additional costs to you or your insurance for these optional studies. You will not be 
paid for taking part. If any of the research leads to new tests, drugs, or other commercial products, 
you will not share in any profits. 
What if I change my mind? 
If you decide you no longer want your samples to be used, you can call the study doctor, 
_________________, (insert name of study doctor for main trial) at ________________________ 
(insert telephone number of study doctor for main trial) who will let the researchers know. Then, 
any sample that remains in the bank will no longer be used and related health information will no 
longer be collected. Samples or related information that have already been given to or used by 
researchers will not be returned. 
What if I have more questions? 
If you have questions about the use of your samples for research, contact the study doctor, 
________________, (insert name of study doctor for main trial), at _____________________ 
(insert telephone number of study doctor for main trial). 
Please circle your answer to show whether or not you would like to take part in each option: 
Samples for future research studies: 
My samples and related information may be donated to ACSR Biobank for use in future 
health research. 
 
YES 
 
 
NO 
I agree to have my samples undergo genetic testing to learn about, prevent, diagnose, or treat 
HIV-related diseases and cancer. 
 
YES 
 
 
NO 
This is the end of the section about optional studies. 
 
 


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MY SIGNATURE AGREEING TO TAKE PART IN THE MAIN STUDY 
I have read this consent form or had it read to me. I have discussed it with the study doctor and my 
questions have been answered. I will be given a signed copy of this form. I agree to take part in 
the study. 
 
Participant’s signature: ________________________________ 
 
Date of signature: _____________________________________ 
 
Signature of person(s) conducting the informed consent discussion: _______________________ 
 
Date of signature: _____________________________________ 


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ATTACHMENT 1: AMC CERTIFICATE OF CONFIDENTIALITY STATEMENT 
The NIH has given the AMC a Certificate of Confidentiality. The Certificate does not mean that 
the NIH or the U.S. Government recommend that you take part in this study. This Certificate helps 
us keep your health information private. 
Your records for this study will have information that may identify you. This Certificate lets us 
turn down legal demands for your study records. We can use the Certificate to turn down demands 
for records from a U.S. court. The Certificate can be used in any federal, state, or local legal 
matters. We will use the Certificate to turn down any demands for your study records. The cases 
where we cannot use the Certificate are explained below. 
We cannot use the Certificate to turn down a demand from the U.S. Government for study records. 
This applies to audits or reviews of the AMC. This also applies to study records that we have to 
report to the FDA. 
The Certificate does not stop you or your family members from sharing your health information. 
It does not stop you from talking about taking part in this study. You may give written permission 
for an insurer, employer, or other person to get copies of your study records. If you give 
permission, we cannot use the Certificate to say no to a request for your study records.