Clinical trial NCT04111107
Conditions: Solid Tumor Lymphoma Multiple Myeloma Malignant Neoplasm Mutation Abnormality
Sponsor: Wake Forest University Health Sciences
Start date: 2020-04-22; Completion date: 2023-02-09
Enrollment: 45 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of the current pragmatic trial is to evaluate the impact of a simple method of selecting a treatment approach for identified mutations on participants' progression free survival (PFS). The study also intends to collect information on barriers that investigators encounter when prescribing treatment options using the Next Generation Sequencing (NGS) reports. Additionally, patients' quality of life will be measured before, after, and during treatment.

Patients will be followed until death for monitoring survival study endpoints.

Detailed description:
Primary Objective:

• To estimate the progression-free ratio, as defined by the progression-free survival time on study treatment divided by the progression-free survival time on the last treatment received by patient, for an identified actionable mutation, who will be treated with an off-label treatment off label therapy based on a simplified selection methodology using the Next Generation Sequencing results.

Secondary Objectives:

* To estimate patient response rate on off-label treatments for actionable mutations based on Next Generation Sequencing results.
* To estimate overall survival (OS) for patients treated with off-label treatments for actionable mutations based on Next Generation Sequencing results.
* To describe the safety of using off-label or other experimental treatments for patients with actionable mutations based on Next Generation Sequencing results.

Exploratory Objectives:

* To describe health related quality of life in patients undergoing off-label treatment targeting genetic mutations, as measured by the PROMIS-29 Overall Health-Related Quality of Life, Including 4-Item Anxiety Subscale.
* Using the Satisfaction with Medical Decision Scale, to describe patient satisfaction with decision to pursue off-label treatment.
* To identify types of actionable mutations with available targeted treatment occurring in cancer patients.
* To characterize the historical treatment regimens for these patients relative to the targetable mutation.
* To describe patient clinical and demographic characteristics of those with actionable mutations based on Next Generation Sequencing results.
* To identify barriers to treatment based on Next Generation Sequencing results.

Arms: arm 1: Investigators will select the first drug listed in the tumor analysis report for the first mutation listed in the tumor analysis report. However, If the subject has a medical contraindication to the first listed drug (according to the drug label) or the first listed drug cannot be obtained for the patient, the study team will select the next drug presented by the tumor sequencing report. Patients receive targeted therapy based on next generation sequencing report. Cycles repeat every 2, 4, or 6 weeks in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Investigational Agent intervention 2: Supportive Care Regimens intervention 3: Next Gen Sequencing Report
Intervention descriptions: intervention 1: Treatment will be administered on an inpatient or outpatient basis based on the type of medication selected. The investigatory will administer the drug as directed in the FDA approved label. intervention 2: Supportive care regimens will vary depending on the type of drug that will be administered at the treating investigator's discretion. intervention 3: 1\) Next Gen Sequencing report obtained as Standard of Care within the past 12 months of enrollment date will be used. If more than one report exists in this time period, the most recent report will be used.

Protocol documents:
Prot_SAP_001.pdf: 
Precision medicine for patients with identified actionable mutations at Wake Forest Baptist 
Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
WFBCCC # 04519 
 
ClinicalTrials.gov:  NCT04111107 
 
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Principal Investigator: 
 
Stefan C. Grant, MBBCh, MD, JD, MBA, FACP, FACLM 
Section on Hematology and Oncology 
Wake Forest School of Medicine 
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
 
 
 
Co-Investigator(s):  
 
Boris Pasche, M.D., Ph.D. 
Director, Wake Forest Baptist Comprehensive Cancer 
Center 
Medical Center Blvd. 
Winston Salem, NC  27157 
 
 
Umit Topaloglu, Ph.D. 
Associate Professor  
Department of Cancer Biology  
Wake Forest Baptist Comprehensive Cancer Center 
 
 
 
 
 
Wake Forest University School of Medicine 
 
 
 
 
 
 
 
 
Wei Zhang, Ph.D. 
Hanes and Willis Family Professor in Cancer 
Director 
Cancer Genomics and Precision Medicine 
Wake Forest Baptist Comprehensive Cancer Center 
Medical Center Boulevard 
Winston-Salem, NC  27157 
 
 
 
Caio Max Sao Pedro Rocha Lima, M.D. 
Section on Hematology and Oncology 
 
 
 
 
 
Wake Forest Baptist Medical Center 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
Lynne Wagner 
Public Health Sciences 
Wake Forest Baptist Medical Center 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biostatistician: 
Emily Dressler, Ph.D. 
Department of Biostatistics and Data Science 


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Wake Forest Baptist Comprehensive Cancer Center 
Wake Forest University School of Medicine 
Medical Center Blvd 
Winston-Salem, NC 27157 
 
 
Study Coordinator:  
 
 
Robin M. Petro, RN 
 
 
 
 
 
Precision Medicine Nurse Navigator 
 
 
 
 
 
 
 
 
Regulatory Contact:  
 
Emmanuel Vazquez 
 
 
 
 
 
Regulatory Specialist I 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Editor: 
 
 
Kathy Walker, BA 
 
 
 
Participating Institution(s): Wake Forest Baptist Comprehensive Cancer Center 
 
 
Original Version Date: 
 
10.03.19 
 
Amended: 
 
12/10/19, 01/08/20, 01/23/20, 06/27/20, 08/07/20, 09/30/20, 03/12/21, 
07/02/21 
 
 
Confidential 
 
 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
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Table of Contents 
1.0 
Introduction and Background ............................................................................................ 6 
2.0 
Objectives ......................................................................................................................... 7 
2.1 
Primary Objective .......................................................................................................... 7 
2.2 
Secondary Objectives ................................................................................................... 7 
2.3 
Exploratory Objectives .................................................................................................. 7 
3.0 
Patient Selection ............................................................................................................... 8 
3.1 
Inclusion Criteria............................................................................................................ 8 
3.2 
Exclusion Criteria .......................................................................................................... 9 
3.3 
Inclusion of Women and Minorities ............................................................................... 9 
4.0 
Registration Procedures .................................................................................................. 10 
5.0 
Study Outcomes and Study Measures ............................................................................ 10 
5.1 
Primary Outcome ........................................................................................................ 10 
5.2 
Secondary Outcomes .................................................................................................. 11 
5.3 
Planned EHR Data Collection ................................................................................... 11 
6.0 
Treatment Plan ................................................................................................................ 12 
6.1 
Treatment Administration ............................................................................................ 17 
6.1.4 
Investigational agent ............................................................................................. 17 
6.2 
General Concomitant Medication and Supportive Care Guidelines ............................ 17 
6.3 
Duration of Therapy..................................................................................................... 17 
6.4 
Duration of Follow Up .................................................................................................. 18 
6.5 
Criteria for Removal from Study .................................................................................. 18 
7.0 
Dosing Delays/Dose Modifications .................................................................................. 18 
8.0 
Measurement of Effect .................................................................................................... 18 
8.1 
Antitumor Effect – Solid Tumors .................................................................................. 18 
8.1.1 
Definitions .............................................................................................................. 19 
8.1.2 
Methods for Evaluation of Measurable Disease .................................................... 20 
8.1.3 
Response Criteria .................................................................................................. 22 
8.1.4 
Survival Outcomes ................................................................................................ 25 
8.1.5 
Response Review ................................................................................................. 25 
8.2 
Antitumor Effect ........................................................................................................... 25 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
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8.3 
Hematologic Tumors ................................................................................................... 25 
8.4 
Neuro-oncology Tumors .............................................................................................. 25 
8.5 
Patient Reported Outcomes ........................................................................................ 25 
9.0 
Adverse Events List and Reporting Requirements ......................................................... 26 
Adverse Events for Off-Label Therapies ................................................................................. 26 
Reporting of Unanticipated Problems, Adverse Events or Deviations ................................ 26 
9.1 
Adverse Event Characteristics .................................................................................... 26 
9.2 
DSMC SAE Reporting Requirements .......................................................................... 26 
9.3 
WFUHS IRB AE Reporting Requirements .................................................................. 27 
10.0 
Pharmaceutical Information ............................................................................................ 27 
10.1 
Pharmaceutical Accountability .................................................................................... 27 
11.0 
Data Management ........................................................................................................... 28 
12.0 
Confidentiality and Privacy .......................................................................................... 28 
13.0 
Data Safety and Monitoring .......................................................................................... 28 
14.0 
Statistical Considerations ................................................................................................ 28 
14.1 
Introduction.................................................................................................................. 28 
14.2 
Analysis of Primary Objective ...................................................................................... 29 
14.3 
Analysis of Secondary and Exploratory Objectives ..................................................... 29 
14.4 
Power and Sample Size .............................................................................................. 29 
14.5 
Estimated Accrual Rate ............................................................................................... 29 
14.6 
Estimated Study Length .............................................................................................. 30 
References .................................................................................................................................. 31 
Appendix  A-Eligibility Checklist .................................................................................................. 32 
Appendix B – Protocol Registration Form ................................................................................... 35 
Appendix C - Race & Ethnicity Verification Form ........................................................................ 36 
Appendix D – DSMC Notification SOP ....................................................................................... 37 
 
 
 
 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
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SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient with Actionable Next Generation Sequencing 
(NGS) identified tumor mutation is identified by the 
Nurse Navigator or via the Electronic Ordering in the 
EMR 
Patients with histologically documented solid tumors, 
lymphomas, or multiple myeloma whose disease has 
progressed following at least two lines of standard 
systemic therapy, who are unable or unwilling to 
receive standard therapy or for whom no standard 
therapy exists 
 
Patient consents to enroll in 
Precision Medicine guided 
treatment 
Patient treated for indicated 
actionable mutation guided by 
Foundation One,CDx Guardant 
360, or other NGS tumor analysis 
outcome report- according to study 
algorithm-  
 
Study follow-up: 
Treatment Received 
Adverse Events 
Response Rate 
Progression-Free Survival 
Quality of Life outcomes 
 
Patient randomized by registrar to 
a number (1-20). A drug treatment 
level (1-4) is randomized. 
 The level of targeted mutation is 
assigned to be the same as the 
patients randomization number. 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
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1.0 
Introduction and Background 
 
Precision medicine is a rapidly growing field with the potential to bypass ineffective 
treatments and target specific genetic mutations present in cancer cells. Although 
clinicians have access to increasing amounts of data regarding tumor genomics, it can 
be problematic to identify a primary driver mutation and the optimal treatment.(Paolillo, 
Londin, & Fortina, 2016). Due to this complexity many clinicians are uncomfortable 
interpreting genomic sequencing results from next generation sequencing assays 
(“NGS”) [J. Clin Oncol 2014, 32, 1317-1323]. I A recent survey of providers at a major 
academic center revealed that more than half the providers were uncomfortable 
interpreting the information from a genomic test [Oncotarget 2017; 8; 27145-27154]. 
Various strategies have been used to facilitate the proper interpretation of genomic data 
including in-person and virtual molecular tumor boards but the limited experience and 
large numbers of permutations with multiple genetic mutations in a single tumor make 
the identification of one or more driver mutations in a particular patient largely a matter of 
an educated guess at best. This has the effect of discouraging the use of targeted 
therapies, that may provide benefit, in patients who have exhausted standard of care 
treatments. Frequently, physicians  prescribe medications off-label in an effort to delay 
progression of disease. Off label prescribing involves prescribing a medication for an 
indication other than the condition for which there is FDA approval.Those physicians 
prescribing targeted therapies off label, based on NGS results face other challenges. 
These includelack of access to available drugs, costs of available drugs, and differing 
reimbursement policies among insurance companies, among others (Messner et al., 
2016)  
 
 
At Wake Forest Baptist Comprehensive Cancer Center (“WFBCCC”), solid tumors are 
most often analyzed using Foundation One CDx, an FDA approved NGS Cancer 
Profiling Test, while liquid samples are primarily analyzed using an assay from Guardant 
360. Other NGS tests employed for tumor analysis include Caris Molecular 
Intelligence®  Comprehensive Tumor Profiling. Results from the testing include any 
identified ,or actionable, genetic mutations and any known drugs with suspected or 
proven efficacy for treating these mutations.  Off-label drug treatment options are 
included in the lab report.  Additionally, any known drugs that lack efficacy for the tumor 
are outlined in the report. For many of the identified mutations, however, no off-label 
drug option is available. 
 
According to WFBCCC data, 9.4% of patients have five or fewer mutations identified in 
their cancer sample, 48.3% have 10 or fewer, 79.1% have 15 or fewer and 87.9% of 
patients who have NGS testing exhibit 20 or more genetic mutations in their cancer 
sample. For many of these mutations, however, no off-label drug is available.  
 
The goal of the current pragmatic trial is to evaluate the impact of a simple method of 
selecting a treatment approach for identified mutations on subjects’ progression free 


Precision medicine for patients with identified actionable mutations at Wake Forest Baptist 
Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
WFBCCC # 04519 
 
ClinicalTrials.gov:  NCT04111107 
 
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survival (PFS) by assigning treatment in a balanced manner when no identified optimal 
off-label treatment is defined. The study also intends to collect information on barriers 
that providers encounter when prescribing treatment options using the NGS reports and 
to measure patients’ quality of life before, after, and during treatment.  
 
2.0 
Objectives 
 
2.1 
Primary Objective 
 
2.1.1 To estimate the progression-free ratio, as defined by the progression-free 
survival time on study treatment divided by the progression-free survival 
time on the last treatment received by patient, for an identified actionable 
mutation, who will be treated with an off-label treatment off label therapy 
based on a simplified selection methodology using the NGS results. 
 
2.2 
Secondary Objectives 
 
2.2.1 To estimate patient response rate on off-label treatments for actionable 
mutations based on NGS results. 
 
2.2.2 To estimate overall survival (OS) for patients treated with off-label 
treatments for actionable mutations based on NGS results. 
 
2.2.3 To describe the safety of using off-label or other experimental treatments 
for patients with actionable mutations based on NGS results. 
 
2.3 
Exploratory Objectives 
 
2.3.1 To describe health related quality of life in patients undergoing off-label 
treatment targeting genetic mutations, as measured by the PROMIS-29 
Overall Health-Related Quality of Life, Including 4-Item Anxiety Subscale.. 
 
2.3.2 Using the Satisfaction with Medical Decision Scale, to describe patient 
satisfaction with decision to pursue off-label treatment. 
 
2.3.3 To identify types of actionable mutations with available targeted treatment 
occurring in cancer patients. 
 
2.3.4 To characterize the historical treatment regimens for these patients 
relative to the targetable mutation. 
 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
WFBCCC # 04519 
 
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2.3.5 To describe patient clinical and demographic characteristics of those with 
actionable mutations based on NGS results. 
 
2.3.6 To identify barriers to treatment based on NGS results. 
3.0 
Patient Selection 
 
3.1 
Inclusion Criteria  
 
3.1.1 Cancer patients at Wake Forest Baptist Comprehensive Cancer Center 
and its satellites who have next generation DNA sequencing results on 
their tumor biopsy or surgically resected tissue and/or blood samples 
and/or consent to the WFCCC Precision Oncology Registry to use their 
information for research. 
 
3.1.2 Actionable mutation (defined as a mutation or gene amplification for which 
an off-label therapy is identified on the patient’s NGS report for which 
NCCN guidelines do not recommend a specific treatment in the particular 
disease or for which there is no documentation in the patient’s medical 
record of clinical data demonstrating lack of activity with the targeting of 
the specific mutation or amplification in the patient’s specific disease) 
uncovered by the genomic sequencing of a tumor or those that have 
undergone  liquid biopsy assay of their tumor genomic, performed by 
Wake Forest or another and who are medically able to receive targeted 
therapy based on those results.  
 
3.1.3 Sequencing on a sample collected within 3 months prior to registration is 
strongly encouraged but must have been performed within the 12 months 
prior to registration. 
 
3.1.4 Patients must have progressed through at least two lines of treatment, or 
are not candidates for or unwilling to receive any standard therapies. 
Patients who have received treatment on the present protocol who have 
progression of disease may be recruited to the trial for treatment using 
another targeted therapy provided that they fullfil the other criteria for 
participation in the trial. If a patient discontinues treatment on this protocol 
they can be considered for further participation in this trial provided they 
meet all of the eligibility criteria and are eligible for re-registration and re-
consent. 
 
 
3.1.5 ECOG of ≤ 3  
 
3.1.6 Life expectancy of greater than 6 weeks 
 


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3.1.7 The effects of the drugs used for cancer treatment on the developing 
human fetus are unknown.  For this reason and because of the possibility 
that the agents are teratogenic, women of child-bearing potential and men 
must agree to use adequate contraception (hormonal or barrier method of 
birth control; abstinence) prior to study entry and for the duration of study 
participation. Should a woman become pregnant or suspect she is 
pregnant while participating in this study, she should inform her treating 
physician immediately. 
 
3.2 
Exclusion Criteria  
 
3.2.1 Patients who have had or will receive chemotherapy or radiotherapy to 
major bone marrow bearing sites within 2 weeks prior to receiving 
treatment on the study. 
 
3.2.2 Patients who have not recovered from  toxicity of prior treatment if such 
toxicity will preclude treatment with the proposed targeted agent. 
 
3.2.3 Patients may not be receiving any other investigational agents. 
 
 
3.2.4 Uncontrolled intercurrent illness including, but not limited to ongoing or 
active infection, symptomatic congestive heart failure, unstable angina 
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that 
would limit compliance with study requirements. 
 
3.2.5 Pregnant women are excluded from this study because of the potential for 
teratogenic or abortifacient effects. Because there is an unknown but 
potential risk for adverse events in nursing infants secondary to treatment 
of the mother with the targeted agent, breastfeeding should be 
discontinued if the mother is treated with the targeted agent. 
 
3.3 
Inclusion of Women and Minorities 
 
 
3.3.1 Women and men of all races and ethnicity who meet the above-described 
eligibility criteria are eligible for this trial.  
 
3.3.2 Based on WFBCCC population estimates, we expect approximately 50% 
of participants to be female, 13% Black or African American, and 6.5% of 
participants to be of Hispanic ethnicity.  3.0% of the remaining minority 
population will be comprised of individuals of other ethnicities. Should we 
not meet or exceed these estimates, the PI will engage the Cancer 
Center Health Equity Advisory Group to discuss strategies to enhance 
recruitment in these target populations. However, the population will 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
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change over time and these estimates may not reflect future ancestral 
distributions in the future. 
4.0 
Registration Procedures 
 
 
All patients entered on any WFBCCC trial, whether treatment, companion, or cancer 
control trial, must be linked to the study in EPIC within 24 hours of Informed Consent. 
Patients must be registered prior to the initiation of treatment.   
 
You must perform the following steps in order to ensure prompt registration of your 
patient: 
 
1. 
Complete the Eligibility Checklist (Appendix A) 
2. 
Complete the Protocol Registration Form (Appendix B) 
3. 
Alert the Cancer Center registrar by phone, and then send the signed Informed 
Consent Form,  
4. 
Eligibility Checklist and Protocol Registration Form to the registrar, either by fax 
or e-mail. 
 
 
Contact Information: 
Protocol Registrar PHONE (336) 713-6767 
Protocol Registrar FAX (336) 713-6772 
Protocol Registrar E-MAIL (registra@wakehealth.edu) 
            
*Protocol Registration is open from 8:30 AM - 4:00 PM, Monday-Friday. 
 
5. Fax/e-mail ALL eligibility source documents with registration. Patients will not be 
registered without all required supporting documents. 
Note: If labs were performed at an outside institution, provide a printout of the results. 
Ensure that the most recent lab values are sent. 
 
To complete the registration process, the Registrar will:   
• 
 
assign a patient study number 
• 
 
assign the patient a drug and dose 
• 
 
register the patient on the study 
5.0 
Study Outcomes and Study Measures 
 
5.1 
Primary Outcome 
 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
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5.1.1 Progression free ratio, defined as the duration of time from start of 
treatment to the time of progression divided by the duration of time from 
the last treatment received pre-trial to the time of progression on that 
treatment. Those that die before progression or are lost to follow-up will 
be non-evaluable for the primary objective.  
5.2 
Secondary Outcomes 
 
5.2.1 Overall survival (OS), defined as the duration of time from the start of 
treatment to date of death or date of last contact; those lost to follow-up 
will be censored.  
 
5.2.2 Investigational Agent Safety To determine incidence of adverse events 
(AEs), serious adverse events (SAEs), and any laboratory abnormalities 
of each investigational agent tested. 
 
5.2.3 To measure response rate of treatment based on a simplified selection 
methodology using the NGS results. 
 
 
5.3 
Planned EHR Data Collection 
 
The following data points will be collected. The NGS data will consist of 
the clinical NGS data report, sequence variant reports (example: VCF or 
variant call files), binary DNA sequence alignment data (BAM files or SAM 
files), and any quality control reports supporting the validity of the clinical 
NGS data. The accompanying clinical data will be extracted from the 
clinical records (through manual and automated processes) and will 
include demographic information, diagnoses, and medical treatments in 
addition to information regarding the relationship of NGS to treatment 
decisions.   
 Age, gender, ethnicity, race, insurance type and coverage 
 Marital status 
 Occupation 
 Educational level 
 Military service 
 Family medical history 
 Patient’s medical history 
• Previous cancer diagnoses and treatments 
• Previous or current conditions  
• Current prescription medications 
 Treating physician and physician ordering tumor DNA sequencing 
 Extent of financial assistance provided if applicable 
 Vendor used for tumor DNA sequencing 


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 Previous and current tobacco and alcohol use information if 
available  
 The date of DNA sequencing results and date of results discussion  
 If NGS data revealed somatic mutations warranting further 
investigation by Genetic Counseling, the type of mutation present 
and the referral date to Genetic Counseling 
 Type of treatment plan toward mutation of interest if 
applicable/known 
 Response and progression-free survival for last known treatment 
 Progression-free and overall survival times for new targeted 
therapy  
 Response to new targeted therapy 
6.0 
Treatment Plan 
 
Patients with actionable tumor mutations who have failed at least two lines of standard of care 
therapy or are unable or unwilling to receive standard therapy and consent to participate will be 
included.  Patients will be treated according to the following algorithm: 
 
1) Next Gen Sequencing report obtained as Standard of Care, preferably within the t 3  
months but necessarily within 12 months prior to of enrollment date will be used .  If 
more than one report exists in this time period, the most recent report will be used.  
2) Patients will be stratified according to whether their NGS assay reports mutation 
frequency or not. 
3) If the assay reports mutation frequency and more than one molecular abnormality is 
identified as actionable the first mutation selected for treatment will be the mutation with 
the reported highest frequency, with subsequentl selections being in order of frequency 
from highest to lowest. 
a. If two or more actionable mutations are reported to have the same frequency 
then, of these, the mutation selected for protocol treatment shall be chosen via 
randomization, as described in 4b-4d below.. 
b. If both mutations and amplifications are reported, mutations shall be selected 
before amplifications. 
c. If two or more amplifications are reported, they shall be selected in the order of 
greatest to least amplification. 
d. If two or more amplifications are reported to have the same degree of 
amplification, of these theamplification selected for protocol treatment  shall be 
chosen via randomization table as in 4b-4d below. 
4) If the assay does not report mutation frequency the initial actionable mutation selected 
will be randomly assigned (in a manner to balance the likelihood of a mutation being 
selected) as follows: 
a. If there is a single actionable mutation that mutation will be selected 
b. If there are 2-5 actionable mutations patient will be randomly assigned a number 
from 1-5 and the first mutation selected will be the mutation corresponding to the 
randomly assigned number. If the randomly assigned number is greater than the 


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Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
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number of actionable mutations, the last listed actionable mutation will be 
selected. 
c.  If there are 6-10 actionable mutations patient will be randomly assigned a 
number from 1-10 and the first mutation selected will be the mutation 
corresponding to the randomly assigned number. If the randomly assigned 
number is greater than the number of actionable mutations, the last listed 
actionable mutation will be selected. 
d. If there are 11-15 actionable mutations patient will be randomly assigned a 
number from 1-15 and the first mutation selected will be the mutation 
corresponding to the randomly assigned number. If the randomly assigned 
number is greater than the number of actionable mutations, the last listed 
actionable mutation will be selected. 
e. If there are  greater than 15 actionable mutations patient will be randomly 
assigned a number from 1-20 and the first mutation selected will be the mutation 
corresponding to the randomly assigned number. If the randomly assigned 
number is greater than the number of actionable mutations, the last listed 
actionable mutation will be selected. 
f. 
If mutations and amplifications of different genes are reported, each shall be 
counted as an actionable mutation.   
 
5) Noting that 87.9% of our patients have 20 or fewer mutations identified, of which many 
are not actionable, it is anticipated that in almost all patients, the probably of an 
actionable mutation being selected will be balanced 
6) Patients will be randomly assigned a second “Treatment Number” from 1-6. 1-6 because 
it is rare for there to be more than 6 drug options for the treatment of an actionable 
mutation.This will be used to select the first chosen drug for treatment of a actionable 
mutation. 
 
7) Once an actionable mutation is selected, if more than one drug is listed as a possible 
treatment, the drug(s) corresponding to the patient’s Treatment Number listed in the 
tumor analysis report for the selected mutation will be selected as treatment. Patients 
must have adequate organ and marrow function to permit administration of the study 
drug as specified in the drug packaging label.  If the subject has a medical 
contraindication to the selected drug (according to the drug label) or the selected 
drug(s)cannot be obtained for the patient, the study team will select the next drug(s) 
presented by the tumor sequencing report.  If necessary, this process will be repeated 
until a suitable drug is selected, returning to the top of the list of the drugs listed for the 
selected mutation if necessary. If the list of drugs proposed for the selected actionable 
mutation is exhausted, then the next listed actionable mutation will be selected and the 
process repeated, if necessary returning to the top of the list of actionable mutations if 
the first selected mutation is not at the top of the list on the report. Documentation for 
why particular drugs were not selected, if applicable, will be obtained for alternative 
Patient has NGS performed as prescribed by their doctor and/or is entered in the Precision Medicine 
RegistryCCCWFU 04218   IRB00054757 
and has failed at least two lines of previous therapy or unable or unwilling to receive standard 
therapy
Is the Mutational Frequency listed on the NGS 
Report? 


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therapies in order to evaluate some of the potential barriers to treatment using the NGS 
method. 
 
 
 
NO 
YES 
If NGS report lists 
the mutational 
frequency, 
targeted mutation 
will be the highest 
frequency 
mutation  
If no mutational 
frequency listed on 
NGS report, the 
actionable mutations 
will be randomly 
assigned, in the order 
below: 


Precision medicine for patients with identified actionable mutations at Wake Forest Baptist Comprehensive 
Cancer Center (WFBCCC): A pragmatic trial 
WFBCCC # 04519 
 
Version Date: 07.02.2021 
 
 
If no mutational frequency listed on NGS report, the actionable mutations will be assigned, in the manner below ( based on 
their presentation in the NGS report): 
If single actionable 
mutation is 
identified  
2-5 actionable 
mutations  
 
6-10 actionable 
mutations  
11-15 actionable 
mutations  
 
>-15 actionable 
mutations  
Single Actionable 
Mutation will be 
targeted 
Patient randomly 
assigned number 
from (1-5). 
Mutations assigned 
a number 
chronologically, 
starting with  first 
presented 
mutation, #1.  
The mutation 
number that is the 
same as the 
randomly assigned 
patient number will 
be targeted.   
For example, for 
patient randomized 
to the number 5, 
the 5th mutation will 
be targeted. 
 
Patient randomly 
assigned number 
from (1-10). 
Mutations assigned 
a number 
chronologically , 
starting with first 
presented 
mutation,#1.  
The mutation 
number that is the 
same as the 
randomized patient 
number will be 
targeted.  
For example, for 
patient randomized 
to number 7, the 7th 
mutation will be 
targeted. 
 
If  randomly 
assigned number is 
greater than 
number of 
actionable 
mutations, the last 
listed actionable 
mutation will be 
selected. 
 
Patient randomly 
assigned number 
from (1-15). 
Mutations assigned 
a number 
chronologically 
starting with the 
first mutation,#1.  
The mutation 
number that is the 
same as the 
randomized patient 
number will be 
targeted.  
For example, for 
patient randomized 
to number 15, the 
15th mutation will 
be targeted. 
 
If  randomly  
assigned number is 
greater than 
number of 
actionable 
mutations, the last 
listed actionable 
mutation will be 
selected. 
 
Patient randomly 
assigned number 
from (1-20). 
Mutations listed on 
the report will be 
assigned a number 
starting with the 
first mutation,#1.  
The mutation 
number that is the 
same as the 
randomized patient 
number will be 
targeted.  
For example, for 
patient randomized 
to number 19, the 
19th mutation will 
be targeted. 
 
If  randomly 
assigned number is 
greater than 
number of 
actionable 
mutations, the last 
listed actionable 
mutation will be 
selected. 
 
All Patients will be randomly assigned a second “Treatment  Medication Number” from 1-6. (it 
is rare for more than 6 drug options for the treatment of an actionable mutation.)  
If more than one drug is listed as possible treatment, the drug corresponding to the patient’s 
Treatment Number (listed in the tumor analysis report for the selected mutation) will be 
selected as treatment. If drug is contraindicated or unattainable for the patient,-the next drug 
on the list will be selected. 


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Study-Related Activities  
 
Pre-Study 
a 
Cycle 2, 
Day 1 
Day 1; 
every even 
cycle 
(after cycle 
2) 
End of 
Treatment 
  +7 days 
Follow up for Safety (30+ 
days after last treatment) 
required only if pt has 
treatment related AEs at 
end of treatment visit 
Informed Consent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History  
X 
 
 
 
 
Concurrent Meds 
X 
 
 
 
 
Physical Exam 
X 
X 
X 
X 
X 
Vital Signs  
X 
X 
X 
X 
X 
Performance Status 
X 
X 
X 
X 
X 
Bone Marrow Biopsy h 
X 
X 
X 
X 
 
Imagingd 
X 
X 
Xf 
X 
 
CBC w/diff, platelets e 
X 
X 
X 
X 
 
X 
Serum Chemistryb 
X 
X 
X 
X 
X 
B-HCGc 
X  
 
 
 
 
Dose Adjustment Form 
 
X 
X 
 
 
Adverse Event 
Evaluation 
 
X 
X 
X 
 
X 
Survival 
Status/Telephone 
Follow up g 
 
 
 
 
 
 
X 
PROMIS 29 
X  
X  
 
X  
 
Satisfaction with 
Medical Decision Scale 
X  
X  
 
X  
 
Patient Reported 
Outcome-
Demographics/Health 
Literacy 
X  
 
 
 
 
a Pre-study requirements listed in table must be completed within 30 days prior to registration. Imaging demonstrating disease progression 
should be completed within 60 days of registration. Imaging should be repeated if the scan occurred more than 30 days prior to treatment 
initiation.. 
b Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total protein, 
SGOT[AST], SGPT[ALT], sodium. 
c Serum pregnancy test within 10 days of Pre-study visit (women of childbearing potential only). 
d Imaging will be performed as part of SOC for solid tumors every other cycle, however due to patients on different drug treatment regimen, 
this may occur at 6 weeks ±2 weeks,, 8 weeks +  2 weeksor 12 weeks + 2 weeks. Not required for leukemias. As clinically indicated in 
Multiple myeloma. 
e Labs will be performed in accordance with the recommendations of the prescribing instructions for the drug that is utilized 
f If treatment is discontinued for reasons other than progression, imaging will be performed on the same schedule as was utilized while 
patient was receiving treatment until progression. 
 g  Survival and information related to cancer treatment received after the study and disease status is monitored bimonthly via telephone 
contact or EMR review after treatment termination. Medical record review will be performed to coincide with the bimonthly telephone call to 
obtain information regarding evidence and of relapse (as documented on CT, PET, biopsy, etc). 
 h If clinically indicated bone marrow biopsy will be repeated to evaluate response to therapy. 


 
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6.1 
Treatment Administration 
 
6.1.1 Treatment will be administered on an inpatient or outpatient basis based on the type of 
medication selected. The physician will administer the drug as directed in theFDA approved 
label. 
 
6.1.2 If the drug is approved with different doses or schedules for different cancers, it will be 
administered according to the indication for the organ system matching that of the patient (if 
available). If not available, the drug will be administered at a dose as as indicated by the 
organ system most closely related to the patients primary disease.  The cycling will be 
determined as directed in Section 6.2.1.  
 
6.1.3 Reported adverse events and potential risks are described in the label and will be 
communicated to the patient at the time of drug selection.  
 
Appropriate dose modifications for the drugs are described in the FDA label and made at 
the treating physician’s discretion.  
 
6.1.4 Investigational agent 
 
The investigational agent in this protocol will be an FDA approved targeted therapy that 
target specific mutations in specific disease.  
Supportive care regimens will vary depending on the type of drug that will be administered 
at the treating physician’s discretion. 
 
6.2 
General Concomitant Medication and Supportive Care Guidelines 
 
Patients should receive full supportive care, including transfusions of blood and blood products, 
erythropoietin, antibiotics, antiemetics, etc., as clinically indicated. Anti-inflammatory or narcotic 
analgesics may be offered as needed. Medications considered necessary for the patient's well-
being may be given at the discretion of the investigator, i.e., chronic treatments for concomitant 
medical conditions, as well as agents required for life-threatening medical problems, etc. The 
reason(s) for treatment, dosage, and dates of treatment should be recorded in the medical record. 
 
6.3 
Duration of Therapy 
 
In the absence of treatment delays due to adverse events, treatment may continue for the number 
of cycles indicated on the FDA label, or until one of the following criteria applies: 
 
• 
Disease progression, 
• 
Intercurrent illness that prevents further administration of treatment, 
• 
Unacceptable adverse event(s), 
• 
Patient decides to withdraw from the study, or 


 
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• 
General or specific changes in the patient's condition render the patient unacceptable for further 
treatment in the judgment of the investigator. 
 
6.4 
Duration of Follow Up 
 
Patients will be followed for adverse events a minimum of 30 days after date of  last study drug 
iadministration, unless otherwise specified in this section of the protocol. Follow-up for serious 
adverse events and mortality after the last study drug dose is administered will take place during 
the routine clinic visits that the patient will have during the 30-day follow-up window (Also 
referenced in Appendix D).  If no visit occurs during this window, a phone call confirmation should 
be made to the patient to determine vital status and whether any adverse events and in particular, 
Grade 4 unexpected adverse events occurred during that window of time and recorded on 
Appendix F.   
 
If a patient is removed from the study, patients will be followed for 30 days after removal from study 
for adverse events. Patients removed from study for unacceptable adverse events will be followed 
until resolution or stabilization of the adverse event. 
 
Patients will be followed until death for monitoring survival study endpoints. 
 
6.5 
Criteria for Removal from Study 
 
Patient refusal to continue on study or unable/unwilling to comply with study procedures. 
 
 
7.0 
Dosing Delays/Dose Modifications 
 
As this protocol will use multiple chemotherapeutic agents Dosing delays and modifications will be made 
as indicated in the FDA label of the drug unless indicated differently by the treating physician. 
8.0 
Measurement of Effect 
 
The response criteria will vary based on the type of cancer being treated. A cache of response forms is in 
Appendix (TBD).  
 
8.1 
Antitumor Effect – Solid Tumors 
 
Response and progression will be evaluated in this study using the Response Evaluation Criteria in 
Solid Tumors (RECIST) criteria 1.1.(Eisenhauer et al., 2009) Changes in the largest diameter 
(unidimensional measurement) of the tumor lesions and the shortest diameter in the case of 
malignant lymph nodes are used in the RECIST criteria.  For diseases where RECIST is not 
employed, response will be measured in accordance with the measurement instrument used for 


 
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that specific disease.  The specific measrurement Criteria being used will be recorded prior to 
treatment 
8.1.1 Definitions  
 
 
 
• 
Evaluable for toxicity:  
All patients will be evaluable for toxicity from the time of their first treatment with the study 
treatment of interest. 
 
• 
Evaluable for objective response: 
Only those patients who have measurable disease present at baseline, have received at least 
one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for 
response.  These patients will have their response classified according to the definitions stated 
below.  (Note:  Patients who exhibit objective disease progression prior to the end of cycle 1 will 
also be considered evaluable.) 
 
• 
Evaluable Non-Target Disease Response.   
Patients who have lesions present at baseline that are evaluable but do not meet the definitions 
of measurable disease, have received at least one cycle of therapy, and have had their disease 
re-evaluated will be considered evaluable for non-target disease.  The response assessment is 
based on the presence, absence, or unequivocal progression of the lesions. 
 
• 
Measurable disease / measurable lesions 
Measurable lesions are defined as those that can be accurately measured in at least one 
dimension (longest diameter to be recorded) as >20 mm by chest x-ray, as >10 mm with CT 
scan, or >10 mm with calipers by clinical exam.  All tumor measurements must be recorded in 
millimeters (or decimal fractions of centimeters). 
 
 
• 
Malignant lymph nodes.   
To be considered pathologically enlarged and measurable, a lymph node must be >15 mm in 
short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater 
than 5 mm).  At baseline and in follow-up, only the short axis will be measured and followed. 
 
• 
Non-measurable disease / non-measurable lesions: 
All other lesions (or sites of disease), including small lesions (longest diameter <10 mm or 
pathological lymph nodes with ≥ 10 to <15 mm short axis), are considered non-measurable 
disease.  Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not 
followed by CT or MRI), are considered as non-measurable. 
 
Note:  Cystic lesions that meet the criteria for radiographically defined simple cysts should not 
be considered as malignant lesions (neither measurable nor non-measurable) since they are, 
by definition, simple cysts. 
 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if non-cystic 
lesions are present in the same patient, these are preferred for selection as target lesions. 
 


 
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• 
Target lesions 
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, 
representative of all involved organs, should be identified as target lesions and recorded and 
measured at baseline.  Target lesions should be selected on the basis of their size (lesions with 
the longest diameter), be representative of all involved organs, but in addition should be those 
that lend themselves to reproducible repeated measurements.  It may be the case that, on 
occasion, the largest lesion does not lend itself to reproducible measurement in which 
circumstance the next largest lesion which can be measured reproducibly should be selected.  
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters.  If lymph nodes are to be 
included in the sum, then only the short axis is added into the sum.  The baseline sum 
diameters will be used as reference to further characterize any objective tumor regression in the 
measurable dimension of the disease. 
 
• 
Non-target lesions 
All other lesions (or sites of disease) including any measurable lesions over and above the 5 
target lesions should be identified as non-target lesions and should also be recorded at 
baseline.  Measurements of these lesions are not required, but the presence, absence, or in 
rare cases unequivocal progression of each should be noted throughout follow-up. 
8.1.2 Methods for Evaluation of Measurable Disease 
 
 
 
• 
Method(s) for obtaining measurements: 
All measurements should be taken and recorded in metric notation using a ruler or calipers.  
All baseline evaluations should be performed as closely as possible to the beginning of 
treatment and never more than 4 weeks before the beginning of the treatment. 
 
The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and during follow-up. Imaging-based 
evaluation is preferred to evaluation by clinical examination unless the lesion(s) being 
followed cannot be imaged but are assessable by clinical exam. 
Clinical lesions:  Clinical lesions will only be considered measurable when they are 
superficial (e.g., skin nodules and palpable lymph nodes) and ≥10 mm diameter as 
assessed using calipers (e.g., skin nodules).  In the case of skin lesions, documentation by 
color photography, including a ruler to estimate the size of the lesion, is recommended. 
 
• 
Time frame for obtaining measurements 
Patients will under imaging every two cycles of therapy ± 10 days until progression. In the 
event that patient discontinues treatment for reasons other than progression, imaging shall 
continue until progression on the same schedule employed while the patient was receiving 
treatment 
 
• 
Use of imaging techniques (e.g., x-ray, CT, MRI, PET) for measuring disease 
Chest x-ray:  Lesions on chest x-ray are acceptable as measurable lesions when they are 
clearly defined and surrounded by aerated lung.  However, CT is preferable.  
 
Conventional CT and MRI:  This guideline has defined measurability of lesions on CT scan 
based on the assumption that CT slice thickness is 5 mm or less.  If CT scans have slice 


 
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thickness greater than 5 mm, the minimum size for a measurable lesion should be twice the 
slice thickness.  MRI is also acceptable in certain situations (e.g. for body scans).   
 
Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, and temporal 
resolution; however, there are many image acquisition variables involved in MRI, which 
greatly impact image quality, lesion conspicuity, and measurement.  Furthermore, the 
availability of MRI is variable globally.  As with CT, if an MRI is performed, the technical 
specifications of the scanning sequences used should be optimized for the evaluation of the 
type and site of disease.  Furthermore, as with CT, the modality used at follow-up should be 
the same as was used at baseline and the lesions should be measured/assessed on the 
same pulse sequence.  It is beyond the scope of the RECIST guidelines to prescribe 
specific MRI pulse sequence parameters for all scanners, body parts, and diseases.  
Ideally, the same type of scanner should be used and the image acquisition protocol should 
be followed as closely as possible to prior scans.  Body 
scans should be performed with breath-hold scanning techniques, if possible. 
 
PET-CT:  At present, the low dose or attenuation correction CT portion of a combined PET-
CT is not always of optimal diagnostic CT quality for use with RECIST measurements.  
However, the CT portion of the PET-CT may be used for RECIST measurements at 
baseline Note, however, that the PET portion of the CT introduces additional data which 
may bias an investigator if it is not routinely or serially performed.   
 
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not be used 
as a method of measurement.  Ultrasound examinations cannot be reproduced in their 
entirety for independent review at a later date and, because they are operator dependent, it 
cannot be guaranteed that the same technique and measurements will be taken from one 
assessment to the next.  If new lesions are identified by ultrasound in the course of the 
study, confirmation by CT or MRI is advised.  If there is concern about radiation exposure at 
CT, MRI may be used instead of CT in selected instances. 
 
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor evaluation 
is not advised.  However, such techniques may be useful to confirm complete pathological 
response when biopsies are obtained or to determine relapse in trials where recurrence 
following complete response (CR) or surgical resection is an endpoint. 
 
FDG-PET:  While FDG-PET response assessments need additional study, it is sometimes 
reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in 
assessment of progression (particularly possible 'new' disease).  New lesions on the basis 
of FDG-PET imaging can be identified according to the following algorithm:  
a. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the positive FDG-PET 
at follow-up corresponds to a new site of disease confirmed by CT, this is PD.  If the 
positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT  scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan).  If the positive FDG-PET at follow-up corresponds to a pre-existing site of 
disease on CT that is not progressing on the basis of the anatomic images, this is not 
PD. 


 
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c. FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy 
in cases where a residual radiographic abnormality is thought to represent fibrosis or 
scarring.  The use of FDG-PET in this circumstance should be prospectively described 
in the protocol and supported by disease-specific medical literature for the indication.  
However, it must be acknowledged that both approaches may lead to false positive CR 
due to limitations of FDG-PET and biopsy resolution/sensitivity. 
  
Note:  A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake 
greater than twice that of the surrounding tissue on the attenuation corrected image. 
 
• 
How tumor markers will be measured and assessed, if applicable 
Tumor markers:  Tumor markers alone cannot be used to assess response.  If markers are 
initially above the upper normal limit, they must normalize for a patient to be considered in 
complete clinical response.  Specific guidelines for both CA-125 response (in recurrent 
ovarian cancer) and PSA response (in recurrent prostate cancer) have been published 
[JNCI 96:487-488, 2004; J Clin Oncol 17, 3461-3467, 1999; J Clin Oncol 26:1148-1159, 
2008].  In addition, the Gynecologic Cancer Intergroup has developed CA-125 progression 
criteria which are to be integrated with objective tumor assessment for use in first-line trials 
in ovarian cancer [JNCI 92:1534-1535, 2000]. 
 
• 
Use of cytology or histology for assessment, if applicable 
Cytology, Histology:  These techniques can be used to differentiate between partial 
responses (PR) and complete responses (CR) in rare cases (e.g., residual lesions in tumor 
types, such as germ cell tumors, where known residual benign tumors can remain). 
 
8.1.3 Response Criteria 
 
• 
Definition of complete response (CR) for target and non-target lesions, as appropriate 
o Target Lesions:  
 
Disappearance of all target lesions and normalization of tumor marker 
level. Any pathological lymph nodes (whether target or non-target) must 
have reduction in short axis to <10 mm (the sum may not be “0” if there 
are target nodes) 
 
Note:  If tumor markers are initially above the upper normal limit, they must 
normalize for a patient to be considered in complete clinical response. 
 
o Non-target lesions:  
 
Disappearance of all non-target lesions and normalization of tumor marker 
level. All lymph nodes must be non-pathological in size (< 10 mm short 
axis) 
 
• 
Definition of partial response (PR) for target and non-target lesions, as appropriate 
o Target lesions:  
 
At least a 30% decrease in the sum of diameters of target lesions, taking as 
reference the baseline sum of diameters 
 
o Non-target lesions 


 
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 
Non-CR/Non-PD: Persistence of 1 or more non-target lesion(s)and/or 
maintenance of tumor marker level above the normal limits 
 
 
• 
Definition of progressive disease (PD) for target and non-target lesions, as appropriate 
o Target Lesions:  
 
> 20% increase in the SLD taking as reference the smallest SLD recorded 
since the treatment started (nadir) and minimum 5 mm increase over the 
nadir 
 
When sum becomes very small, increases within measurement error (2-3 
mm) can lead to 20% increase 
 
(Note:  the appearance of one or more new lesions is also considered 
progressions) 
 
o Non-target lesions: 
 
Unequivocal progression of existing non-target lesions. The appearance of 
one or more new lesions. 
 
Unequivocal progression should not normally trump target lesion status.  It 
must be representative of overall disease status change, not a single lesion 
increase 
 
Although a clear progression of “non-target” lesions only is exceptional, the 
opinion of the treating physician should prevail in such circumstances, and 
the progression status should be confirmed at a later time by the review 
panel (or Principal Investigator). 
 
• 
Definition of stable disease (SD) for target and non-target lesions, as appropriate 
o Target lesions:  
 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify 
for PD, taking as reference the smallest sum diameters while on study 
 
• 
Definition and evaluation of best overall response, if applicable 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The patient's best response 
assignment will depend on the achievement of both measurement and confirmation criteria. 
 
Best Overall Response Table When Confirmation of CR or PR is required  
 
Overall Response 
First Timepoint 
Overall Response 
Subsequent Timepoint 
BEST overall response 
CR 
CR 
CR 
CR 
PR 
SD, PD, OR PR 
CR 
SD 
SD provided minimum criteria for SD 
duration are met. Otherwise PD 
CR 
PD 
SD provided minimum criteria for SD 
duration are met. Otherwise PD 


 
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CR 
NE 
SD provided minimum criteria for SD 
duration are met. Otherwise NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD 
duration are met. Otherwise PD 
PR 
NE 
SD provided minimum criteria for SD 
duration are met. Otherwise NE 
NE 
NE 
NE 
 
Overall Response Table for Patients with Measurable Disease 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Response for this Category 
Also Requires: 
CR 
CR 
No 
CR 
>4 wks. confirmation 
CR 
Non-
CR/Non-PD 
No 
PR 
 
>4 wks. confirmation 
CR 
NE 
No 
PR 
PR 
Non-PD or 
NE 
No 
PR 
SD 
Non-PD or 
NE 
No 
SD 
documented at least once >4 wks. 
from baseline 
Not all 
evaluated 
Non-PD 
No 
NE 
 
PD 
Any 
Yes or No 
PD 
 
no prior SD, PR or CR 
Any 
PD* 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
*In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 
 
Note: Patients with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be reported 
as “symptomatic deterioration”.  Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
 
Overall Response Table for Patients with Non-Measurable Disease (i.e., Non-Target Disease)  
 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 


 
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*  ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease 
since SD is increasingly used as an endpoint for assessment of efficacy in 
some trials so to assign this category when no lesions can be measured is 
not advised 
 
 
8.1.4 Survival Outcomes 
 
Progression-Free Survival is defined as the duration of time from the start of treatment to the time 
of progression, death, or date of last contact; those lost to follow-up will be censored. 
 
Progression-Free Ratio is defined as the duration of time from start of treatment to the time of 
progression divided by the duration of time from the last treatment received pre-trial to the time of 
progression on that treatment. Those that die before progression or are lost to follow-up will be 
non-evaluable for the primary objective.(Cirkel et al., 2016) 
 
Overall Survival is defined as the duration of time from the start of treatment to date of death or 
date of last contact; those lost to follow-up will be censored. 
8.1.5 Response Review 
 
All radiologic reads will be performed by radiologists with expertise in the evaluation of tumor size 
by RECIST or particular response criteria used for evaluation of response in the particular tumor 
type.  
 
8.2 
Antitumor Effect  
When part of standard of care, specific tumor markers may be measured and if measured will be 
recorded but tumor response for solid tumors will be based in RECIST criteria. 
8.3 
Hematologic Tumors 
 
 
Antitumor Effect for Hematologic measures will be evaluated using existing standard Hematologic 
 
 
 
Response Criteria and will be defined prior to the intiation of therapy.  
8.4 
Neuro-oncology Tumors 
. 
Antitumor effect for Neuro-oncology tumors will be evaluated using the RANO Criteria {Wen, 2010 
#8}. 
 
8.5 
Patient Reported Outcomes 
 
Baseline patient health literacy will be measured using a three item Health Literacy Scale. Quality 
of Life will be evaluated using the PROMIS-29 with the 4 point Anxiety Subscale.  To measure 
patient’s satisfaction with their decision to pursue next generation sequencing and subsequent 
therapy, the 5 item Satisfaction with Medical Decision Scale, will be used. 


 
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9.0 
Adverse Events List and Reporting Requirements 
 
Adverse Events for Off-Label Therapies 
The adverse events associated with the targeted or off-label therapeutic agents will vary. These will 
be outlined to the patient by the treating physician. As per WFCCC standard of care, patients will 
be provided with a document that explains the adverse events associated with the medication 
prescribed. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
 
Any unanticipated problems deviations or changes will be promptly reported by the principal 
investigator or designated member of the research team to the IRB and sponsor or 
appropriate government agency if appropriate. 
 
9.1 
Adverse Event Characteristics 
 
• 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in the 
revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be 
utilized for AE reporting. All appropriate treatment areas should have access to a copy of the 
CTCAE version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web 
site (http://ctep.cancer.gov). 
 
• 
‘Expectedness’: AEs can be ‘Unexpected’ or ‘Expected’ for expedited reporting purposes only.   
 
• 
Attribution of the AE: 
 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
9.2 
DSMC SAE Reporting Requirements 
 
The Data Safety Monitoring Committee (DSMC) is responsible for reviewing SAEs for WFBCCC 
Institutional studies as outlined in Appendix D. All Adverse Events that occur during protocol 
intervention and are coded as either 1) unexpected grade 4, 2) unplanned inpatient hospitalization  
≥ 24 hours (regardless of grade), or grade 5 (death) must be reported to the DSMC using the SAE 
consol in WISER.  


 
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All WFBCCC Clinical Protocol and Data Management (CPDM) staff members assisting a Principal 
Investigator in investigating, documenting and reporting an SAE qualifying for DSMC reporting are 
responsible for informing a clinical member of the DSMC as well as the entire committee via the 
email notification procedure of the occurrence of an SAE.  
9.3 
WFUHS IRB AE Reporting Requirements 
 
Any unanticipated problems involving risks to subjects or others and adverse events shall be 
promptly reported to the IRB, according to institutional policy. Reporting to the IRB is required 
regardless of the funding source, study sponsor, or whether the event involves an investigational or 
marketed drug, biologic or device. Reportable events are not limited to physical injury, but include 
psychological, economic and social harm. Reportable events may arise as a result of drugs, 
biological agents, devices, procedures or other interventions, or as a result of questionnaires, 
surveys, observations or other interactions with research subjects. 
 
All members of the research team are responsible for the appropriate reporting to the IRB and 
other applicable parties of unanticipated problems involving risk to subjects or others. The Principal 
Investigator, however, is ultimately responsible for ensuring the prompt reporting of unanticipated 
problems involving risk to subjects or others to the IRB. The Principal Investigator is also 
responsible for ensuring that all reported unanticipated risks to subjects and others which they 
receive are reviewed to determine whether the report represents a change in the risks and/or 
benefits to study participants, and whether any changes in the informed consent, protocol or other 
study-related documents are required. 
 
Any unanticipated problems involving risks to subjects or others occurring at a site where the study 
has been approved by the WFUHS IRB (internal events) must be reported to the WFUHS IRB 
within 7 calendar days of the investigator or other members of the study team becoming aware of 
the event. 
 
Any unanticipated problems involving risks to subjects or others occurring at another site 
conducting the same study that has been approved by the WFUHS IRB (external events) must be 
reported to the WFUHS IRB within 7 calendar days of the investigator or other members of the 
study team becoming aware of the event. 
 
Any event, incident, experience, or outcome that alters the risk versus potential benefit of the 
research and as a result warrants a substantive change in the research protocol or informed 
consent process/document in order to insure the safety, rights or welfare of research subjects. 
10.0 Pharmaceutical Information 
10.1 Pharmaceutical Accountability 
 
The targeted off-label chemotherapeutic or immunotherapy agents are commercially available. 
Their description, use, preparation, administration, storage and stability parameters are outlined in 
the package insert. Disposal of remaining portions of the agents should be done per the Wake 
Forest Waste Stream. 


 
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11.0 Data Management 
 
Informed consent document 
EPIC 
Patient Demographics and clinical data 
WISER/OnCore, REDCap 
Current Medications List 
WISER/OnCore 
NGS Result 
NGS Database 
Patient Withdrawal Form  
WISER/OnCore 
Adverse Events Log 
WISER/OnCore 
Vitals 
WISER/OnCore 
30 day Treatment Follow-up Form 
WISER/OnCore 
Evaluation of Best Overall Response 
WISER/OnCore 
Off-Study Form 
WISER/OnCore 
Study Medication Form 
REDCap 
PROMIS 29 
REDCap 
Satisfaction with Medical Decision Scale 
REDCap 
Patient Reported Outcome-Demographics 
REDCap 
Telephone Follow up Form 
REDCap 
Health Literacy Questionnaire 
REDCap 
12.0 Confidentiality and Privacy  
 
One risk inherent in this project is the loss of confidentiality. Confidentiality will be protected by collecting 
only information needed to assess operational outcomes and maintaining all study information in a 
secure manner. Data will be collected on an identifiable level. Following data collection, the data will be 
kept indefinitely. Data access will be limited to registry staff (Investigators, CPDM staff, and patient 
navigators). Data and records will be kept password protected, in OnCore (WISER), REDCap and the 
NGS database. No reference to any individual participant will appear in reports, presentations, or 
publications that may arise from the collection of this data. The data could be used for a research study. 
Data will only be given to the research study by the registry staff upon an IRB approval. The Registry 
staff will serve as honest brokers of the data. All data provided for research will be completely 
deidentified.  
13.0 Data Safety and Monitoring 
 
The principal investigator will be responsible for the overall monitoring of the data of participants.  
 
14.0 Statistical Considerations 
 
 
14.1 Introduction 
 


 
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It should be noted that the primary analyses for this protocol are examining whether the process of using 
next generation sequencing methods to identify a potential treatment for patients who have failed previous 
ttherapies have any clinically beneficial effects.  The goal is not to evaluate a particular treatment per se, 
but rather an approach to assign a treatment to patients using next generation sequencing methods. 
 
14.2 Analysis of Primary Objective 
 
 
The primary objective of this non-randomized, single-arm pragmatic trial is to estimate the progression-free 
ratio as defined by the duration of time from start of treatment to the time of progression divided by the 
duration of time from the last treatment received pre-trial to the time of progression on that treatment. 
Those that die before progression or are lost to follow-up will be non-evaluable for the primary objective. 
The median progression-free ratio will be estimated with the range and a two-sided Wilcoxon Signed Rank 
test will be calculated to see if the PFS ratio is different from 1.0.  
14.3 Analysis of Secondary and Exploratory Objectives 
 
Response rate will be estimated for all patients with corresponding 95% confidence intervals. Progression-
free survival and overall survival times will be displayed using Kaplan-Meier curves with median survival 
times and confidence intervals. Adverse events will be summarized in incidence tables by type and grade 
severity for all patients and presented by type of treatment received. For exploratory objectives, the 
frequency of types of actionable mutations and previous treatment history will be summarized and 
demographic characteristics presented. Logistic models will be constructed for each type of mutation 
(yes/no) to preliminarially explore associations with clinical and demographic characteristics. For quality of 
life and patient satisfaction outcomes, changes over time will be assessed using a repeated measures 
ANOVA, with any between time associations utilizing Tukey adjustment for post-hoc comparisons. 
Transformations and/or non-parametric approaches will be considered for any outcomes violating 
parametric assumptions. 
14.4 Power and Sample Size 
 
This trial is powered to detect differences in the progression-free ratio for those with actionable mutations 
identified by NGS results and then treated with a targeted therapy. A hypothesized PFS ratio larger than 
1.3 would suggest that the targeted therapy is doing better than the previous treatment received (not 
targeted), and we assume a null hypothesis PFS ratio of 1.0 (no difference). Using pilot data seen in Von 
Hoff et al, we assume a conservative standard deviation of 1.71. With 269 evaluable participants, we have 
80% power to detect differences in PFS ratio from 1.0 to 1.3, assuming a two-sided Wilcoxon test with 
level of significance equal to 0.05. This does assume the actual underlying distribution is normal, but 
powers for a non-parametric Wilcoxon test. ("PASS 16 Power Analysis and Sample Size Software," 
2018)As those that die before progression or are lost to follow-up will be non-evaluable for the primary 
objective, we conservatively allow for 20% non-evaluable. Therefore, we plan to recruit 337 total patients in 
this trial. 
 
14.5 Estimated Accrual Rate 
 
The WFCCC Precision Oncology Registry plans to accrue approximately 50 participants per month. We 
anticipate approximately 20-30% of those will have an actionable mutation identified from NGS that can be 
treated with a targeted therapy, i.e. 10-15 a month. 


 
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14.6 Estimated Study Length 
 
Given anticipated accrual rates of 10-15 per month, it should take around 2– 3 years to enroll 337 patients.  
 


 
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References 
 
Cirkel, G. A., Weeber, F., Bins, S., Gadellaa-van Hooijdonk, C. G., van Werkhoven, E., Willems, S. M., . . . Voest, 
E. E. (2016). The time to progression ratio: a new individualized volumetric parameter for the early 
detection of clinical benefit of targeted therapies. Ann Oncol, 27(8), 1638-1643. 
doi:10.1093/annonc/mdw223 
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., . . . Verweij, J. (2009). New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer, 45(2), 
228-247. doi:10.1016/j.ejca.2008.10.026 
Messner, D. A., Al Naber, J., Koay, P., Cook-Deegan, R., Majumder, M., Javitt, G., . . . McGuire, A. (2016). 
Barriers to clinical adoption of next generation sequencing: Perspectives of a policy Delphi panel. Appl 
Transl Genom, 10, 19-24. doi:10.1016/j.atg.2016.05.004 
Paolillo, C., Londin, E., & Fortina, P. (2016). Next generation sequencing in cancer: opportunities and challenges 
for precision cancer medicine. Scand J Clin Lab Invest Suppl, 245, S84-91. 
doi:10.1080/00365513.2016.1210331 
 PASS 16 Power Analysis and Sample Size Software. (2018). Kaysville, Utah UA: NCSS, LLC. Retrieved from 
ncss.com/software/pass  
 
 
 
 
 
 
 
 


 
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Appendix  A-Eligibility Checklist 
 
 
IRB Protocol No.  
WFBCCC Protocol No.04519 
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Principal Investigator:  Stefan C. Grant, MD 
 
Inclusion Criteria 
(as outlined in study protocol) 
Criteria 
is met 
Criteria is 
NOT met 
Source Used to Confirm * 
(Please document dates and lab results) 
Cancer patients at Wake Forest Baptist 
Comprehensive Cancer Center and its satellites 
who have next generation DNA sequencing 
results on their tumor biopsy or surgically 
resected tissue and/or blood samples and /or 
consent to the WFCCC Precision Oncology 
Registry to use their information for research. 
□ 
□ 
 
Actionable mutation (defined as a mutation or 
amplification for which an off-label therapy is 
identified on the patient’s NGS report for which 
NCCN guidelines do not recommend a specific 
treatment in the particular disease or for which 
there is no documentation in the patient’s medical 
record of clinical data demonstrating lack of 
activity with the targeting of the specific mutation 
in the patient’s specific disease) uncovered by the 
genomic sequencing of a tumor or those that 
have undergone  liquid biopsy assay of their 
tumor genomic, performed by Wake Forest or 
another and who are medically able to receive 
targeted therapy based on those results 
□ 
□ 
 
Sequencing on a sample collected within 3 
months prior to registration is strongly 
encouraged but must have been performed within 
the 12 months prior to registration. 
□ 
□ 
 
Patients must have progressed through at least 
two lines of treatment, or are not candidates for or 
unwilling to receive any standard therapies. 
Patients who have received treatment on the 
present protocol who have progression of disease 
may be recruited to the trial for treatment using 
another targeted therapy provided that they fullfill 
the other criteria for participation in the trial. If a 
patient discontinues treatment on this protocol 
they can be considered for further participation in 
this trial provided they meet all of the eligibility 
criteria and are eligible for re-registration and re-
consent. 
□ 
□ 
 
ECOG of ≤ 3  
□ 
□ 
 


 
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Life expectancy of greater than 6 weeks 
□ 
□ 
 
The effects of the drugs used for cancer treatment 
on the developing human fetus are unknown. For 
this reason, and because of the possibility that the 
agents are teratogenic, women of child-bearing 
potential and men must agree to use adequate 
contraception (hormonal or barrier method of birth 
control; abstinence) prior to study entry and for 
the duration of study participation. Should a 
woman become pregnant or suspect she is 
pregnant while participating in this study, she 
should inform her treating physician immediately. 
□ 
□ 
 
Exclusion Criteria 
(as outlined in study protocol) 
Criteria 
NOT 
present 
Criteria is 
present 
Source Used to Confirm * 
(Please document dates and lab results) 
Patients who have had or will have chemotherapy 
or radiotherapy to major bone bearing sites within 
2 weeks prior to receiving treatment on the study 
 
□ 
□ 
 
Patients who have not recovered from toxicity of 
prior treatment if such toxicity will preclude 
treatment with the proposed targeted agent. 
□ 
□ 
 
Patients may not be receiving any other 
investigational agents 
□ 
□ 
 
 
□ 
□ 
 
Uncontrolled intercurrent illness including, but not 
limited to ongoing or active infection, symptomatic 
congestive heart failure, unstable angina pectoris, 
cardiac arrhythmia, or psychiatric illness/social 
situations that would limit compliance with study 
requirements. 
□ 
□ 
 
Pregnant women are excluded from this study 
because of the potential for teratogenic or 
abortifacient effects. Because there is an 
unknown but potential risk for adverse events in 
nursing infants secondary to treatment of the 
mother with the targeted agent, breastfeeding 
should be discontinued if the mother is treated 
with the targeted agent. 
□ 
□ 
 
 
This subject is      
 eligible /  ineligible     for participation in this study. 
 
OnCore Assigned PID: ___ ___ ___ ___ ___ ___ ___ ___  
 
 
 
 
 
 
 
 
Signature of research professional confirming eligibility: _______________________  
 
Date: ___ ___ / ___ ___ / ___ ___ 
 
Signature of Treating Physician:  _____________________________________  
 
Date:  ___ ___ / ___ ___ / ___ ___ 


 
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Signature of Principal Investigator**:  _____________________________________  
 
Date:  ___ ___ / ___ ___ / ___ ___ 
 
* Examples of source documents include clinic note, pathology report, laboratory results, etc. When listing the source, 
specifically state which document in the medical record was used to assess eligibility. Also include the date on the 
document. Example: “Pathology report, 01/01/14” or “Clinic note, 01/01/14” 
 
**Principal Investigator signature can be obtained following registration if needed 
 


 
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Appendix B – Protocol Registration Form 
 
DEMOGRAPHICS 
Patient: Last Name: _____________________ First Name: ___________________________ 
MRN:          ___ ___ ___ ___ ___ ___ ___ ___ DOB (mm/dd/yy): ___ ___ / ___ ___ / ___ ___ 
ZIPCODE:  ___ ___ ___ ___ ___ 
 
 
SEX:   
  Male      Female 
Ethnicity (choose one):   Hispanic 
Non-Hispanic 
Race (choose all that 
apply): 
 WHITE           BLACK            ASIAN 
 PACIFIC ISLANDER                 NATIVE AMERICAN 
Height:   ___ ___.___ inches 
Weight: ___ ___ ___.___lbs.(actual) 
Surface Area: ___ ___.___m2   
 
Primary Diagnosis: ____________________________________________________________ 
Date of Diagnosis: ___ ___ /___ ___/___ ___ 
 
Performance Status: ___  ECOG   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Registrar can be contact by calling 336-713-6767 between 8:30 AM and 4:00 PM, Monday – Friday. 
 
Compete the eligibility checklist in WISER and then give the completed Eligibility Checklist and Protocol Registration Form 
must be hand delivered, faxed or e-mailed to the registrar at 336-713-6772 or registra@wakehealth.edu, respectively. 
 
 
PROTOCOL INFORMATION 
Date of Registration: 
___ ___ / ___ ___ / ___ ___ 
MD Name (last) : 
______________________       
Date protocol treatment started: 
___ ___ / ___ ___ / ___ ___ 
Informed written consent: 
(consent must be signed prior to registration) 
 YES   NO 
 
Date Consent Signed: 
___ ___ / ___ ___ / ___ ___ 
 
PID # (to be assigned by OnCore): 
___ ___ ___ ___ ___ ___ ___ ___ 
 


 
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Appendix C - Race & Ethnicity Verification Form 
 
 
Thank you so much for helping us to verify your race and ethnicity to ensure the quality of our 
information. As a brief reminder, the information you provide today will be kept confidential. 
 
1. Are you: 
Hispanic or Latino/a 
Not Hispanic or Latino/a 
 
2. What is your race? One or more categories may be selected. 
White or Caucasian 
Black or African American 
American Indian or Alaskan Native 
Asian 
Native Hawaiian or Other Pacific Islander 
Other, Please Specify: ___________________________ 
          
 
 
Internal use only: 
 
 
 Name: ____________________ MRN#: ____________________  
 
Was the self-reported race and ethnicity of the participant verified at the time of consent? 
Yes        No 
 
Was a discrepancy found?       Yes         No 
         If yes, please provide what is currently indicated in the EMR:  
 
 
Ethnicity: ____________________  
Race: ____________________ 
Additional comments: __________________________________________________________________ 
_____________________________________________________________________________________ 
_____________________________________________________________________________


 
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Appendix D – DSMC Notification SOP 
 
  
Data and Safety Monitoring Committee 
(DSMC) Serious Adverse 
Event (SAE) Notification SOP  
Date: 03/12/2021  
  
Mandatory DSMC SAE Reporting Requirements in WISER 
This document describes reporting requirements of adverse events from WFBCCC 
Investigator Initiated interventional trials to the Data and Safety Monitoring Committee 
(DSMC). A trial is considered a WFBCCC Investigator Initiated interventional trial if the 
following criteria are met: 
 
1) The Principal Investigator (PI) of the trial is a member of a department at the 
Wake Forest University Baptist Medical Center. 
2) WFBCCC is considered as the primary contributor to the design, implementation 
and/or monitoring of the trial. 
3) The trial is designated as “Interventional” using the Clinical Research 
Categories definitions provided by the NCI in the Data Table 4 
documentation. 
(https://cancercenters.cancer.gov/GrantsFunding/DataGuide#dt4) 
 
There are two distinct types of WFBCCC Investigator Initiated interventional trials based 
on where patient enrollment occurs.  These include: 
 
1) Local WFBCCC Investigator Initiated interventional trials defined as trials where all 
patients are enrolled from one of the WFBCCC sites. These include the main 
outpatient Cancer Center clinics (located in Winston-Salem) as well as WFBCCC 
affiliate sites located in Bermuda Run (Davie Medical Center), Clemmons, 
Lexington, High Point, or Wilkesboro. 
2) Multi-Center WFBCCC Investigator Initiated interventional trials defined as trials 
where patients are enrolled from other sites in addition to WFBCCC sites.   
There are three types of trials that are included in this category: 
a. Trials sponsored by the NCI Community Oncology Research Program 
(NCORP) that are conducted at multiple sites where the PI is a member of a 
department at the Wake Forest University Baptist Medical Center. 
b. Trials sponsored by Industry that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center. 
c. Trials sponsored by WFBCCC that are conducted at multiple sites and the 
PI is a member of a department at the Wake Forest University Baptist 
Medical Center. 


 
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All Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur on any patients 
enrolled on WFBCCC Investigator Initiated Interventional trials must be entered into the 
WISER system. The only exception to this requirement is for patients enrolled on NCORP 
trials at non- WFBCCC sites. AEs and SAEs for NCORP patients enrolled at WFBCCC sites 
must be entered into the WISER system. Once these AEs and SAEs are entered in WISER, 
certain actions must be taken regarding the reporting of specific Adverse Events to the 
DSMC. 
 
 
 
All Adverse Events that occur during protocol intervention (defined below) and are coded 
as either 1) unexpected grade 4, 2) unplanned inpatient hospitalization > 24 hours 
(regardless of grade), or grade 5 (death) must be reported to the DSMC using the using 
the SAE console in WISER. 
 
A research nurse or clinical research coordinator when made aware that an adverse event 
meets one of the above criteria has occurred on a WFBCCC Investigator Initiated 
interventional trial, is responsible for informing a clinical member of the DSMC by phone 
(or in-person) about the adverse event. The nurse/coordinator should contact the treating 
physician prior to calling the DSMC clinical member to obtain all details of the SAE, as well 
as all associated toxicities to be recorded along with the SAE. In addition, this nurse or 
coordinator is responsible for entering the adverse event information into the SAE console 
in WISER.  Once the adverse event has been entered into the SAE console an email 
informing the entire DSMC will be generated. 
 
THESE REPORTING REQUIREMENTS APPLY TO any staff member on the study team for a WFBCCC 
Institutional Interventional trial. Ultimately, the protocol PI has the primary responsibility for AE 
identification, documentation, grading and assignment of attribution to the investigational 
agent/intervention. However, when an AE event as described above is observed, it is the 
responsibility of the person who observed the event to be sure that it is reported to the DSMC. 
 
What is considered during protocol intervention? 
During protocol intervention is considered to be the time period while a patient is on study 
treatment or during the time period within 30 days of last study treatment (even if patient 
begins a new (non-study) treatment during the 30 days). This window of 30 days should be 
the standard window to be used in all protocols unless a specific scientific rationale is 
presented to suggest that a shorter window can be used to identify events. If it is a trial 
sponsored by Industry and the sponsor requires a longer window for monitoring of SAEs, 
then the longer window of time specified by the sponsor should be followed. 
 
What is considered as an Unexpected Grade 4 event? 


 
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Any grade 4 event that was not specifically listed as an expected adverse event in the 
protocol should be considered as unexpected. A grade 4 adverse event can be considered to 
be unexpected if it is an event that would not be expected based on the treatment being 
received or if it is unexpected based on the health of the patient. In either case, if there is 
any uncertainty about whether a grade 4 adverse event is expected or unexpected it should 
be reported to DSMC. 
 
DSMC notification responsibilities of the person (e.g., nurse) handling the reporting/documenting of 
the SAE in WISER: 
1. Make a phone call (or speak in person) to the appropriate clinical member of the 
DSMC according to the schedule as listed below (page if necessary). 
2. Enter a new SAE into the SAE module that is located in the Subject>> CRA Console in 
WISER WITHIN 24 HOURS of first knowledge of the event. Information can be 
entered and saved, but the DSMC members will not be notified until a date is 
entered into the  DSMC Notification Date Field. This will ensure that all persons that 
need to be made aware of the event (i.e., PI, study team members and DSMC 
members) will be notified; remember to file a copy of the confirmation. 
3. Document that the appropriate person(s) on the DSMC has been contacted. Indicate 
the name of the DSMC clinician that was contacted and the date and time contacted 
in the Event Narrative field in the SAE console of the particular subject. 
4. Document whether or not the protocol should be suspended based on the 
discussion with the DSMC clinician. This is the major function of the email 
notification. Enter whether the protocol should be suspended in the Event Narrative 
Field. 
5. Follow up/update the clinical member(s) of DSMC regarding any new developments 
or information obtained during the course of the SAE investigation and reporting 
process. 
 
Elements needed to complete the SAE form in the Subject Console in WISER (see Screen Shot 3): 
1. Event Date 
2. Reported Date 
3. Reported by 
4. If Grade 5, enter Death Date 
5. If Grade 5, enter Death occurred: within 30 days 
6. Event Narrative: Brief description (include brief clinical history relevant to this event, 
including therapies believed related to event). Begin narrative with the DSMC clinician 
who was notified and Date/Time notified. In addition, state attribution by DSMC 
clinician as either “Unrelated”, “Unlikely”, “Possibly”, “Probably”, or “Definitely”.  
Always include the following here: 
i. DSMC clinician name, date/time contacted and comments 
ii. Date of last dose before the event 
iii. Is suspension of the protocol needed? Y/N 


 
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7. Treating Physician comments 
8. PI comments, if available 
9. Protocol Attribution after discussion with DSMC clinician 
10. Outcome (Fatal/Died, Intervention for AE Continues, Migrated AE, Not Recovered/Not 
Resolved, Recovered/Resolved with Sequelae, Recovered/Resolved without Sequelae, 
Recovering and Resolving) 
11. Consent form Change Required? Y/N 
12. SAE Classification *This is required in order for the email notification to be sent* 
13. Adverse Event Details – Enter all details for each AE associated with the SAE. 
a. Course start date 
b. Category 
c. AE Detail 
d. Comments 
e. Grade/Severity 
f. Unexpected Y/N 
g. DLT Y/N 
h. Attributions 
i. Action 
j. Therapy 
k. Click ADD to attach the AE Detail to the SAE. 
14. Enter Date Notified DSMC -- *This is required for the email notification to be sent* 
15. Click Submit. The auto-generated notification email will disseminate within 5 minutes. 
If you do not receive an email within 5 minutes, check that you have entered the 
“Date Notified DSMC” and the “SAE Classification”. If these have been entered and 
the email still has not been received, take a screen shot of the SAE in WISER and 
immediately email it out to all of the DSMC members listed in this SOP. In the subject 
line, indicate that this is a manual transmission of the SAE in lieu of the auto-
generated email. It is required that a notification goes to the DSMC members 
immediately so that their assessment can be obtained within the 24 hour period 
requirement. Contact the Cancer Center Programmer/Analyst to alert that there is an 
issue with the auto-generated email. 
 
The Clinical Members of DSMC to Notify by Phone or Page: 
 
Monday 
Tuesday 
Wednesday Thursday 
Friday 
Saturday Sunday 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes Goodman 
Reed 
Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed Porosnicu 
Seegars 
Lesser 
Hughes 
Goodman 
Reed 
Porosnicu Seegars 
 
Glenn Lesser, MD – Hematology Oncology 6-9527 / 6-7972 / Pager 336-806-8397  


 
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Mercedes Porosnicu, MD-- Hematology Oncology 6-7980 / 6-0230 / Pager 336-806-9150 
Ryan Hughes, MD – Radiation Oncology 3-3600 / Pager 336-806-9865 
Michael Goodman, MD -- Hematology Oncology 6-7970 / Pager 336-806-7283 
Daniel Reed, MD -- Hematology Oncology 3-3841 / Pager 336-806-0637 
Mary Beth Seegars, MD -- Hematology Oncology 6-4815 / Pager 336-806-9948 
 
 
Definition of Unavailable: 
As a general guideline if the first clinician that is contacted does not respond to the phone 
call or page within 30 minutes, then initiate contact with the next DSMC clinician listed in the 
table above on the particular day the SAE is being reported. Allow up to 30 minutes for the 
new DSMC clinician to respond to a phone call or page before contacting the next member in 
the table. These times (30 minutes) are a general guideline. Best judgment as a clinical 
research professional should be used giving considerations of the time of day, severity of the 
SAE, and other circumstances as to when it is appropriate to contact backup clinicians. If the 
event occurs near the end of day, then leave messages (voice or email) as appropriate and 
proceed with submitting the DSMC notification form. It is important to take reasonable steps 
and to document that some type of contact has been initiated to one or more of the clinical 
members of DSMC. 
 
DSMC CLINICAN RESPONSIBILITY: 
It is the responsibility of the DSMC clinician to review all reported events, evaluate the events 
as they are reported; and communicate a response to the Investigator, event reporter and 
the members of DSMC. The review will include but not be limited to the information 
reported; there may be times when additional information is needed in order for an 
assessment to be made and further communication directly with the investigator may be 
warranted. DSMC reserves the right to disagree with the Investigator's assessment. If DSMC 
does not agree with the Investigator, DSMC reserves the right to suspend the trial pending 
further investigation. If there is any immediate danger or harm that could be present for a 
future patient based on the information provided in the DSMC report then an immediate 
suspension of enrollment should be considered. 
 
 
AMENDMENTS TO PREVIOUS REPORTS 
If all pertinent information is unavailable with the initial submission, once the additional 
information is available do not submit a new report. Rather, go to the original email that 
was sent to the DSMC and using that email “reply to all”. Entitle this new email 
“Amendment for (list date of event and patient ID)” this will avoid duplications of the same 
event. List the additional information being reported. This information needs to be entered 
into WISER as well. To do this, go to the Subject console and click SAEs on the left column. 
Click on the appropriate SAE number that needs updating. Then click Update. This will allow 
additional  information to be added. 
 


 
Precision medicine for patients with identified actionable mutations at Wake Forest Baptist 
Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
WFBCCC # 04519 
 
Version Date: 07.02.2021                                          Page Page 42 of 44 
 
 
Acronyms 
AE – Adverse Event 
DSMC-Data and Safety Monitoring Committee 
SAE-Serious Adverse Event 
WFBCCC – Wake Forest Baptist Comprehensive Cancer Center 
NCI-National Cancer Institute 
WISER –Wake Integrated Solution for Enterprise Research 
Screen Shots:  
  
The following screen shots come from the SAE Console within the Subject Console in WISER.  
  
Screen Shot 1:  
  
  
  
 
 
Screen Shot 2:  


 
Precision medicine for patients with identified actionable mutations at Wake Forest Baptist 
Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
WFBCCC # 04519 
 
Version Date: 07.02.2021                                          Page Page 43 of 44 
 
  
  
 
 
 
 
Screen Shot 3: 
 
 
 
Screen Shot 4: 
 


 
Precision medicine for patients with identified actionable mutations at Wake Forest Baptist 
Comprehensive Cancer Center (WFBCCC): A pragmatic trial 
WFBCCC # 04519 
 
Version Date: 07.02.2021                                          Page Page 44 of 44 
 
 
 

ICF_000.pdf: 
Official Title:Precision Medicine for Patients With Identified Actionable Mutations 
at Wake Forest Baptist Comprehensive Cancer Center (WFBCCC): A Pragmatic 
Trial
NCT04111107
IRB-Approved Date:  10/6/22


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 1 of 13
Adult Consent Form
Version 01/08/2020
Department/Section of Hematology & Oncology
PRECISION MEDICINE FOR PATIENTS WITH IDENTIFIED ACTIONABLE 
MUTATIONS AT WAKE FOREST BAPTIST COMPREHENSIVE CANCER 
CENTER (WFBCCC): A PRAGMATIC TRIAL
Informed consent to participate in research
WFBCCC # 04519
Stefan C. Grant, MD, JD, MBA, Principal Investigator (PI)
SUMMARY
You are invited to participate in a research study. The purpose of this research study is to 
determine how feasible it is to use Next Generation Tumor analysis to direct your cancer care. 
You are invited to be in this study because your body has not responded to at least two previous 
cancer therapies and you have had a test performed on a tumor sample of your cancer.  The test 
on your tumor sample was to identify any changes in the tumor that are different from your 
normal genetic material.  These changes are called mutations. Your physician has received a 
report about changes that were identified and some drug recommendations based on these 
changes.  Sometimes the recommended drugs may not be approved by the FDA for your 
particular cancer, but there may be scientific evidence that suggests that the drug could be 
helpful.  The length of participation in this study will vary for each person and will be 
determined by the number of treatment cycles you receive.
Participation in this study will involve allowing the Investigator to make recommendations for 
your cancer care using information learned from the reports about the genetics of your cancer.  
All research studies involve some risks.  A risk to this study that you should be aware of is that 
the treatment chosen from your tumor mutation report using methods developed in this study 
may cause your cancer to worsen or may change nothing about your current cancer status.  
Additionally, there may be side effects due to the different types of drugs used to treat the 
cancer. However, there is a possibility that you may benefit from participation in this study.  
Your participation in this study is voluntary.  You do not have to participate in this study if you 
do not want to.  There may be other choices available to you.  Some other choices may include 
receiving the same drugs without participating in a study, participating in a different research 
study, or receiving comfort care for your cancer.  You will not lose any services, benefits, or 
rights you would normally have if you choose not to participate. 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 2 of 13
Adult Consent Form
Version 01/08/2020
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions if you need help deciding whether to join the 
study. The person in charge of this study is Dr. Stefan Grant. If you have questions, 
suggestions, or concerns regarding this study or you want to withdraw from the study his/her 
contact information is 
.
If you have any questions, suggestions or concerns about your rights as a volunteer in this 
research, contact the Institutional Review Board at 
2 or the Research Subject 
Advocate at Wake Forest at 
.
INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this 
study because you have cancer that has not responded to previous treatment or has recurred after 
a previous treatment and you have had molecular genetic testing performed on a piece of your 
cancer  tissue. Your participation is voluntary. Please take your time in making your decision as 
to whether or not you wish to participate. Ask your study doctor or the study staff to explain any 
words or information contained in this informed consent document that you do not understand. 
You may also discuss the study with your friends and family.
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to test the effect of using drugs targeted at genetic 
mutations as well as the method of choosing the best treatment option for you based on a 
genetics report. 
As part of your routine cancer care, you recently have had or will have a tumor (or bone marrow) 
biopsy performed.  Samples from this biopsy are sent to a company (either Foundation One, 
Caris, or Guardant360) and DNA testing is done on them.  The results of this testing are sent 
back to your cancer physician in a report with a list of genetic mutations in your tumor that might 
respond better to specific (targeted) chemotherapies.  If you would like a copy of this genetics 
report, your physician can provide one for you.  This can be done whether or not you participate 
in this study.  You are eligible for this study if:  a) you have a mutation listed on the genetics 
report that does not have an FDA-approved treatment regimen, b) you have already completed a 
non-FDA-approved treatment regimen and your cancer did not respond to it, or c) you are 
medically unable to receive an FDA-approved treatment for your condition. 
Genetic testing of cancer tumors is a relatively new process. Although a lot of information is 
learned from this testing, doctors do not always know what the best approach for treatment of 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 3 of 13
Adult Consent Form
Version 01/08/2020
cancer is.  This is because tumors can have many different kinds of genetic mutations and there 
is not always a known treatment for these mutations.  
For this study, the treating physician will select a medication for your treatment based on the 
report’s genetic information about your cancer and a new method that the investigators have 
developed for interpreting the report’s results.  Ultimately, your physician will choose the best 
drug(s) possible for your overall medical situation and health care coverage. The investigators 
will also collect information about your health and any side effects that occur on any of the 
medication(s) prescribed.
Drugs used in this study have been approved by the US Food and Drug Administration (FDA), 
but may not have been approved for use in your particular cancer.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
337 people at this research site will take part in this study.
WHAT IS INVOLVED IN THE STUDY?
After your study doctor has answered all your questions about this study and you have given 
written consent by signing this form, several tests will be done to be sure you are able to enter 
this study. Many of the tests are the same as those you have had in the past to diagnose and treat 
your disease. Some of these same tests will also be done during the study to follow your 
progress. 
Pre-Study Tests
The following tests may be completed over a four-week period before receiving medication:

If your doctor has been monitoring your cancer with CT scans, you will undergo an 
imaging scan known as a CT scan. A CT scan uses computers and x-rays to take detailed 
pictures of areas inside your body. 

If you have a hematologic malignancy such as leukemia or myeloma and your doctor has 
been following your disease with bone marrow biopsies, you will undergo a bone marrow 
biopsy.

The study doctor or study staff will ask you about your medical history, and obtain a list 
of all medications that you are currently taking.

The study doctor or study staff will examine you and determine your performance status.

A physical examination with your vital signs (heart rate, blood pressure, breathing rate, 
and body temperature), will be recorded.

You will be asked about any problems you are having with your medication.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 4 of 13
Adult Consent Form
Version 01/08/2020

You will be asked to complete some surveys that ask questions about your medical care, 
your day to day activities, and your emotional health.  These surveys usually take about 
30 minutes to complete.
The following test must be completed within one week before receiving medication:

Pregnancy test for women who can become pregnant. This must be done within one 
week of starting treatment. 
If the results of these tests show that you are eligible to enroll in this study, your participation on 
the study can begin. 
You will be randomized into one of the study groups described below. Randomization means 
that you are put into a group by chance. It is like flipping a coin. You will be randomized based 
on the number of genetic mutations present on your tumor report. This is because researchers do 
not know which mutation is more important to treat. The drug chosen for your treatment will 
also be from your tumor report. It will be chosen randomly.  For example, if the report lists 4 
different drugs that have shown effectiveness in fighting a certain type of mutation, you will be 
randomly assigned to receive one of these 4 drugs.
Study Treatment and Procedures
This clinical research study consists of multiple (three, four or six-week) cycles of treatment with 
a medication selected by one of the doctors participating in this study. Cycle length will be 
determined by prescribing information for the specific medication that you will receive.
Study Visits
You will have a Pre-Study visit before you start the study. Your next visit will be in four to six 
weeks.   At this visit, you will receive the following:

If applicable, you will undergo an imaging scan known as a CT scan. A CT scan uses 
computers and x-rays to take detailed pictures of areas inside your body. 

The study doctor or study staff will ask you about your medical history, and obtain a list 
of all medications that you are currently taking.

The study doctor or study staff will examine you and determine your performance status.

A physical examination with your vital signs (heart rate, blood pressure, breathing rate, 
and body temperature), will be recorded.

You will be asked about any problems you are having with your medication.

You will be asked to complete some surveys that ask questions about your medical care, 
your day to day activities, and your emotional health.  These surveys usually take about 
30 minutes to complete.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 5 of 13
Adult Consent Form
Version 01/08/2020
Your remaining visits will be scheduled every 6-12 weeks for as long as you are receiving 
benefit from the medication.  At these visits, the following will occur:

If applicable, you will undergo an imaging scan known as a CT scan. A CT scan uses 
computers and x-rays to take detailed pictures of areas inside your body. 

The study doctor or study staff will ask you about your medical history, and obtain a list 
of all medications that you are currently taking.

The study doctor or study staff will examine you and determine your performance status.

A physical examination with your vital signs (heart rate, blood pressure, breathing rate, 
and body temperature), will be recorded.

You will be asked about any problems you are having with your medication.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 6  of 13
Adult Consent Form
Version 01/08/2020
Schedule of events
a Pre-study requirements listed in table must be completed within 30 days prior to registration.
b If clinically indicated as part of your Standard Care
c Follow up visit will happen at least 30 days after your end of treatment visit *only* if you were 
experiencing side effects at your end of treatment visit
End of Treatment Visit
When you decide to leave the study or when your cancer stops responding to the medication, you 
will be asked to return for a final study visit.  At this visit, you will be asked to complete surveys 
about your health.  You will also receive a physical exam at this time.
Telephone Follow up
After you complete treatment, the study team would like to follow up with you every 2 months.  
Every 2 months, someone from the study team will call to check in with you. 
Pre-
Study
a
Cycle 
2, Day 
1
Day 1 of 
every 
even 
cycle 
(after 
cycle 2)
End of 
Treatment
  +7 days
Follow Up 
Visit c 
Bimonthly 
after End 
of 
Treatment
Informed 
Consent
X
Medical 
History
X
Physical 
Exam
X
X
X
X
X
Vital Signs 
X
X
X
X
X
Imagingb  
X
X
X
X
Bone Marrow 
Biopsyb 
X
X
X
X
Lab work
X
X
X
X
Pregnancy 
Test for 
women who 
can become 
pregnant
X 
Adverse 
Event 
Evaluation
X
X
X
X
Surveys
X 
X 
X 
Telephone 
Follow Up
X
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 7  of 13
Adult Consent Form
Version 01/08/2020
HOW LONG WILL I BE IN THE STUDY?
The length of participation in this study will vary for each person and will be determined by the 
number of treatment cycles you receive. All participants will be in the study until it is determined 
that your cancer is no longer responding to treatment. 
For example, if the PET/CT scan that is performed at the end of cycle two shows that your 
cancer has responded to treatment, you will receive two more cycles of treatment. If the scan 
shows that your cancer has stopped responding, you will not receive any further treatment. 
Once you have finished treatment as part of this study, you will receive a phone call from the 
research staff once every two months to check and see how you are doing if you do not return to 
the clinic for follow-up. These phone calls will continue long term as long as you give 
permission.
If your initial medication does not show any effect on your cancer, it is possible for you to try a 
different medication based on your cancer genetics. 
In addition, you can stop participating at any time. It is important to tell the study doctor if you 
are thinking about stopping so that any risks from your medication can be evaluated by your 
study doctor. Another reason to tell your study doctor that you are thinking about stopping is to 
discuss what follow-up care and testing could be most helpful for you.
You can stop participating at any time. If you decide to stop participating in the study we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. 
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you.  There is a risk that your cancer will not respond to 
treatment long-term, at all, or it may get worse.  Receiving targeted chemotherapy based on 
genetic mutations in your cancer is not a guarantee that the treatment will work.  It is possible 
that only some of your tumor’s cells will have the mutation being targeted, there may be no 
evidence that the drug(s) chosen for you will work on your specific type of cancer, or that your 
tumor cells will/could continue to change and become unresponsive to the drug(s) chosen for 
you.  There may also be side effects associated with your chosen medication(s). You should 
discuss the risk of being in this study with the study staff and your physician. Specific risks and 
side effects related to your condition and specific medication(s) will be provided to you before 
you begin treatment and you will be able to discuss these with the prescribing physician.
In addition, there is a slight risk of a breach of confidentiality.  We will do our best to protect 
your confidential information.  There also may be other risks that we cannot predict. You should 
tell the research staff about all the medications, vitamins and supplements you take and any 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 8  of 13
Adult Consent Form
Version 01/08/2020
medical conditions you have. This may help avoid side effects, interactions and other risks.
Taking part in this research study may involve providing information that you consider 
confidential or private.  Efforts, such as coding research records, keeping research records secure 
and allowing only authorized people to have access to research records, will be made to keep 
your information safe.
Reproductive Risks and other Issues to Participating in Research
Due to unknown risks and potential harm to the unborn fetus, sexually active women of 
childbearing potential must use a reliable method of birth control while participating in this 
study. Reliable methods of birth control are: abstinence (not having sex), oral contraceptives, 
OrthoEvra patch, NuvaRing, intrauterine devices (IUD), Nexplanon implant, DepoProvera, tubal 
ligation, or vasectomy of the partner (with confirmed negative sperm counts) in a monogamous 
relationship (same partner). An acceptable, although less reliable, method involves the careful 
use of condoms and spermicidal foam or gel and/or a diaphragm with spermicide with Plan B 
used for any noticed condom or diaphragm failures. We encourage you to discuss this issue 
further with your physicians if you have any questions.
Pregnant women are excluded from participation in this study. Because NO method of birth 
control is 100% reliable, a pregnancy test is required within 10 days of the pre-study visit.
Contraceptive Measures for Males
Your participation in this research study may damage your sperm, which could cause harm to a 
child that you may father while on this study. Such harm may be currently unforeseeable. If you 
are sexually active, you must agree to use a medically acceptable form of birth control in order to 
be in this study and for (at least 6 months afterwards. Medically acceptable contraceptives 
include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide. 
Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are 
not acceptable methods for routine use. You should inform your partner of the potential for harm 
to an unborn child. She should know that if pregnancy occurs, you will need to report it to the 
study doctor, and she should also promptly notify her doctor.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may or may not be direct benefit to you. We hope the 
information learned from this study will benefit other people in the future. The benefits of 
participating in this study may be: a delay in the return of your cancer. 
WHAT OTHER CHOICES ARE THERE?
You do not have to be in this study to receive treatment. You should talk to your doctor about all 
the choices you have. Instead of being in this study, you have these options:
You could receive treatment outside of the study based on your physician’s discretion.  You may 
participate in another research study or you may choose to receive comfort care for your cancer.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 9  of 13
Adult Consent Form
Version 01/08/2020
 WHAT ARE THE COSTS?
You or your insurance company will be responsible for all of the medical care you receive.  The 
study doctors will seek out every chance to get your insurance to cover the costs for your chosen 
treatment or to get you financial assistance through one of our patient assistance programs.
WILL YOUR RESEARCH RECORDS BE CONFIDENTIAL?
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals.  Your identity and/or your personal health information will not be disclosed 
unless it is authorized by you, required by law, or necessary to protect the safety of yourself or 
others.  There is always some risk that even de-identified information might be re-identified. 
Participant information may be provided to Federal and other regulatory agencies as required.  
The Food and Drug Administration (FDA), for example, may inspect research records and learn 
your identity if this study falls within its jurisdiction.
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health. The researchers with this Certificate may not disclose or use information, documents, or 
biospecimens that may identify you in any federal, state, or local civil, criminal, administrative, 
legislative, or other action, suit, or proceeding, or be used as evidence, for example, if there is a 
court subpoena, unless you have consented for this use. Information, documents, or 
biospecimens protected by this Certificate cannot be disclosed to anyone else who is not 
connected with the research except, if there is a federal, state, or local law that requires 
disclosure (such as to report child abuse or communicable diseases but not for federal, state, or 
local civil, criminal, administrative, legislative, or other proceedings, see below); if you have 
consented to the disclosure, including for your medical treatment; or if it is used for other 
scientific research, as allowed by federal regulations protecting research subjects. 
The Certificate cannot be used to refuse a request for information from personnel of the United 
States federal or state government agency sponsoring the project that is needed for auditing or 
program evaluation by the National Cancer Institute which is funding this project or for 
information that must be disclosed in order to meet the requirements of the federal Food and 
Drug Administration (FDA).  You should understand that a Certificate of Confidentiality does 
not prevent you from voluntarily releasing information about yourself or your involvement in 
this research. If you want your research information released to an insurer, medical care 
provider, or any other person not connected with the research, you must provide consent to allow 
the researchers to release it.
WILL YOU BE PAID FOR PARTICIPATING?
You will not be paid for participating in this study. Parking validation will be provided for all 
study-related visits.
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 10  of 13
Adult Consent Form
Version 01/08/2020
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by Wake Forest Baptist Comprehensive Cancer Center. The 
sponsor is providing money or other support to Wake Forest University Health Sciences to help 
conduct this study. However, the researchers do not hold a direct financial interest in the sponsor 
or the product being studied.
WHAT HAPPENS IF YOU EXPERIENCE AN INJURY OR ILLNESS AS A 
RESULT OF PARTICIPATING IN THIS STUDY?
Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance 
coverage for the usual and customary medical fees for reasonable and necessary treatment of 
such injuries or illnesses. To the extent research insurance coverage is available under this policy 
the reasonable costs of these necessary medical services will be paid, up to a maximum of 
$25,000. Wake Forest University Baptist Medical Center holds the insurance policy for this 
coverage. It provides a maximum of $25,000 coverage for each claim and is limited to a total of 
$250,000 for all claims in any one year. The Wake Forest University School of Medicine, and 
the North Carolina Baptist Hospitals, Incorporated do not assume responsibility to pay for these 
medical services or to provide any other compensation for such injury or illness. Additional 
information may be obtained from the Medical Center’s Director of Risk and Insurance 
Management, at 
If you are injured, the insurer may require information such as your name, social security 
number, and date of birth in order to pay for your care.  This is because the insurer is required by 
law to report any payments made to cover the care of any persons who are members of a 
government insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For 
more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should call Dr. Stefan Grant at 
 or After Hours 
at 
.
WHAT ABOUT MY HEALTH INFORMATION?
In this research study, any new information we collect from you and/or information we get from 
your medical records or other facilities about your health or behaviors is considered Protected 
Health Information. The information we will collect for this research study includes: information 
about your medical visits, information from your imaging scans, and information regarding your 
cancer and treatment of your cancer.
If this research study involves the diagnosis or treatment of a medical condition, then Protected 
Health Information collected from you during this study will be placed in your medical record, 
and may be used to help treat you, arrange payment for your care, or assist with Medical Center 
operations. We will make every effort to keep your Protected Health Information private. We 
will store records of your Protected Health Information in a cabinet in a locked office or on a 
WFU School of Medicine 
Institutional Review Board 
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Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 11  of 13
Adult Consent Form
Version 01/08/2020
password protected computer. 
Your personal health information and information that identifies you (“your health information”) 
may be given to others during and after the study. This is for reasons such as to carry out the 
study, to determine the results of the study, to make sure the study is being done correctly, to 
provide required reports and to get approval for new products.  
Some of the people, agencies and businesses that may receive and use your health information 
are the research sponsor; representatives of the sponsor assisting with the research; investigators 
at other sites who are assisting with the research; central laboratories, reading centers or analysis 
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA) or the Office of Human Research Protections (OHRP), 
the Department of Health and Human Services (DHHS) and similar agencies in other countries.  
Some of these people, agencies and businesses may further disclose your health information. If 
disclosed by them, your health information may no longer be covered by federal or state privacy 
regulations.  Your health information may be disclosed if required by law. Your health 
information may be used to create information that does not directly identify you. This 
information may be used by other researchers. You will not be directly identified in any 
publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable.
If required by law or court order, we might also have to share your Protected Health Information 
with a judge, law enforcement officer, government agencies, or others. If your Protected Health 
Information is shared with any of these groups it may no longer be protected by federal or state 
privacy rules.
Any Protected Health Information collected from you in this study that is maintained in the 
research records will be kept for an indeterminate period of time. This authorization does not 
expire.  Any research information entered into your medical record will be kept for as long as 
your medical record is kept by the Medical Center. You will not be able to obtain a copy of your 
Protected Health Information in the research records until all activities in the study are 
completely finished. 
You can tell Dr. Grant that you want to take away your permission to use and share your 
Protected Health Information at any time by sending a letter to this address:
Stefan C. Grant, MD, JD, MBA
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 12  of 13
Adult Consent Form
Version 01/08/2020
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for this 
study.
If you choose to participate in this study, your medical record at Wake Forest University Baptist 
Medical Center will indicate that you are enrolled in a clinical trial.  Information about the 
research and any medications or devices you are being given as a participant may also be 
included in your medical record.  This part of the medical record will only be available to people 
who have authorized access to your medical record.  If you are not a patient at this Medical 
Center, a medical record will be created for you anyway to ensure that this important information 
is available to doctors in case of an emergency.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This website will not include information that can identify you.  At most, the 
website will include a summary of the results.  You can search this Web site at any time. 
Laboratory test results and other clinically relevant medical reports created as a result of your 
participation in the research study may be entered into the computer systems of Wake Forest 
University Health Sciences and North Carolina Baptist Hospital.  These will be kept secure, with 
access to this information limited to individuals with proper authority, but who may not be 
directly involved with this research study.
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study 
participants. Information about your participation in the study will be placed in the NCBH 
medical record, along with any routine medical test results that were obtained at NCBH as part 
of this study. 
WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the 
study at any time. Refusing to participate or leaving the study will not result in any penalty or 
loss of benefits to which you are entitled. If you decide to stop participating in the study, we 
encourage you to talk to the investigators or study staff first to learn about any potential health or 
safety consequences. The investigators also have the right to stop your participation in the study 
at any time. This could be because such as, it is in your best medical interest, your condition 
worsened, new information becomes available, you had an unexpected reaction, you failed to 
follow instructions, or because the entire study has been stopped.  Information that identifies you 
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023


Wake Forest Baptist Comprehensive Cancer Center (WFBCCC)
WFBCCC #04519
Page 13  of 13
Adult Consent Form
Version 01/08/2020
may be removed from the data or specimens that are collected as part of this study and could be 
used for future research or shared with others without additional consent. 
You will be given any new information we become aware of that would affect your willingness 
to continue to participate in the study.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or in the event of a research-related injury, contact the study 
investigator, Dr. Stefan Grant at 
 or after-hours at 
.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
 or the 
Research Subject Advocate at 
.
You will be given a copy of this signed consent form. 
SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form.  If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me.  I have had a chance to 
ask questions about being in this study and have those questions answered.   By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):_____________________________
Subject Signature: _________________________________ Date: ________Time:_______ am pm 
Person Obtaining Consent (Printed):_____________________________
Person Obtaining Consent:___________________________ Date:_________ Time:________ am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number:IRB00061185
Meeting Date Approved 10/6/2022          
Version Valid Until: 10/5/2023