Clinical trial NCT03845296
Conditions: Deleterious BRCA1 Gene Mutation Deleterious BRCA2 Gene Mutation Loss of Heterozygosity Lung Non-Small Cell Squamous Carcinoma Recurrent Large Cell Lung Carcinoma Recurrent Lung Adenocarcinoma Recurrent Lung Non-Small Cell Carcinoma Recurrent Non-Squamous Non-Small Cell Lung Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8
Sponsor: SWOG Cancer Research Network
Start date: 2019-04-16; Completion date: 2024-09-21
Enrollment: 64 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II Lung-MAP trial studies how well rucaparib works in treating patients with genomic loss of heterozygosity (LOH) high and/or deleterious BRCA1/2 mutation stage IV non-small cell lung cancer or that has come back. Rucaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description:
PRIMARY OBJECTIVES:

I. To evaluate the overall response rate (ORR) (confirmed and unconfirmed, complete and partial) associated with rucaparib in patients with genomic LOH high and/or deleterious BRCA1/2 mutations within: Cohort 1: Patients with squamous cell histology or mixed histology with a squamous component; Cohort 2: Patients with non-squamous histology (adenocarcinoma, large cell, or non-small cell lung cancer \[NSCLC\] not otherwise specified \[NOS\]).

SECONDARY OBJECTIVES:

I. To evaluate investigator assessed progression-free survival (IA-PFS) and overall survival (OS) associated with rucaparib within each cohort.

II. To evaluate duration of response among responders within each cohort. III. To evaluate the frequency and severity of toxicities associated with rucaparib among all patients enrolled on the study (combining cohorts).

TRANSLATIOAL MEDICINE OBJECTIVES:

I. To evaluate the association between alterations in deoxyribonucleic acid (DNA) repair genes and response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To perform comprehensive next-generation sequencing of circulating tumor DNA (ctDNA) at baseline in all patients to assess its clinical utility in comparison to tumor tissue biomarker profiles.

III. To establish a tissue/blood repository from patients with refractory non-small cell lung cancer (NSCLC).

OUTLINE:

Patients receive rucaparib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for up to 3 years.

Arms: arm 1: Patients receive rucaparib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Rucaparib
Intervention descriptions: intervention 1: Given PO

Protocol documents:
Prot_SAP_000.pdf: 
 
S1900A 
 
Page 1 
 
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PRIVILEGED COMMUNICATION 
FOR INVESTIGATIONAL USE ONLY 
 
S1900A: LOH high and/or deleterious BRCA1/2 mutation - Rucaparib 
 
SWOG 
 
TITLE 
LUNGMAP, A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND 
IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (Lung-MAP 
SCREENING STUDY) 
 
S1900A, A PHASE II STUDY OF RUCAPARIB IN PATIENTS WITH GENOMIC LOH HIGH AND/OR 
DELETERIOUS BRCA1/2 MUTATION STAGE IV OR RECURRENT NON-SMALL CELL LUNG 
CANCER (Lung-MAP SUB-STUDY) 
 
NCT#: 03845296 
 
Clovis Oncology Protocol #: 338-IIT-094 
 
This is a potential FDA Registration Trial. Additional site requirements include: 
• maintenance of a Trial Master File (https://www.swog.org/sites/default/files/docs/2017-
10/Guidance%20on%20FDA%20Inspection.pdf)  
• completion of a protocol specific Delegation of Task Log (DTL) (see Section 13.2) 
• additional monitoring (see LUNGMAP Appendix 18.2) 
 
NOTE: Sites must utilize the CIRB as their IRB of record to participate in this study. 
 
LUNGMAP and its sub-studies are being conducted under SWOG IND 143217 and CIRB. The 
LUNGMAP Study is considered a single study under one IND, consisting of the Screening 
Protocol and multiple sub-studies. Each sub-study protocol operates independently and has its 
own version date. For CIRB Continuing Reviews, LUNGMAP and its sub-studies will be processed 
separately but have the same expiration date as the LUNGMAP screening protocol. 
 
 
SUB-STUDY CHAIRS: 
 
Jonathan W. Riess, M.D. (Medical Oncology)  
NCTN Group:  SWOG 
UC Davis Comprehensive Cancer Center  
Division of Hematology/Oncology  
2279 45th Street  
Sacramento, CA 95817 
Phone: 916/734-3772 
FAX: 916/734-7946 
E-mail: jwriess@ucdavis.edu  
 
Paul Wheatley-Price, M.D. (Medical Oncology) 
NCTN Group: CCTG 
University of Ottawa 
Ottawa Hospital Cancer Centre, Box 944 
501 Smyth Road 
Ottawa, ON 
Canada K1H 8L6 
Phone: 613/737-7700 
E-mail: pwheatleyprice@toh.ca   
STUDY AGENTS: 
 
Available from Pharmaceutical Collaborators: 
Rucaparib (CO-338, AG-014447,  
PF-01367338) (NSC804038)  
(Distributed by NCI, DCTD) 
 
BIOSTATISTICIANS: 
Mary Redman, Ph.D. 
Katherine Minichiello, M.S. 
Jieling Miao, M.S. 
James Moon, M.S. 
SWOG Statistics & Data Management Center 
1100 Fairview Ave N, M3-C102 
Seattle, WA 98109-1024 
Phone: 206/667-4623 
FAX: 206/667-4408 
E-mail: mredman@fredhutch.org  
E-mail: kmini@fredhutch.org  
E-mail: jmiao@fredhutch.org   
E-mail: jmoon@fredhutch.org   


 
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PARTICIPANTS 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALLIANCE/Alliance for Clinical Trials in Oncology 
ECOG-ACRIN/ECOG-ACRIN Cancer Research Group 
NRG/NRG Oncology 
SWOG/SWOG 


 
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TABLE OF CONTENTS 
 
TITLE  ………………………………………………………………………………………………………………..1 
PARTICIPANTS 
............................................................................................................................................ 2 
TABLE OF CONTENTS ............................................................................................................................... 3 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
....................... 5 
SCHEMA 
....................................................................................................................................................... 6 
1.0 
OBJECTIVES .................................................................................................................................. 7 
1.1 
Primary Objective 
............................................................................................................................. 7 
1.2 
Secondary Objectives 
...................................................................................................................... 7 
1.3 
Translational Medicine Objectives 
................................................................................................... 7 
2.0 
BACKGROUND 
............................................................................................................................... 7 
2.1 
Overview .......................................................................................................................................... 7 
2.2 
Rationale 
........................................................................................................................................ 
10 
2.3 
Data 
................................................................................................................................................ 
11 
2.4 
Feasibility ....................................................................................................................................... 
15 
2.5 
Inclusion of Women and Minorities and Planned Enrollment Report ............................................ 
16 
3.0 
DRUG INFORMATION 
.................................................................................................................. 
16 
3.1 
Rucaparib (Rubraca ®) (NSC 804038) (IND-143217) 
................................................................... 
17 
4.0 
STAGING CRITERIA 
..................................................................................................................... 
22 
5.0 
ELIGIBILITY CRITERIA ................................................................................................................ 
23 
5.1 
Sub-Study Specific Criteria 
............................................................................................................ 
23 
5.2 
Common Eligibility Criteria for all Sub-Studies .............................................................................. 
24 
5.3 
Specimen Submission Criteria 
....................................................................................................... 
26 
5.4 
Regulatory Criteria 
......................................................................................................................... 
27 
6.0 
STRATIFICATION FACTORS 
....................................................................................................... 
27 
7.0 
TREATMENT PLAN 
...................................................................................................................... 
27 
7.1 
Disease Assessment 
...................................................................................................................... 
27 
7.2 
Precautions .................................................................................................................................... 
28 
7.3 
Pre-Medication 
............................................................................................................................... 
28 
7.4 
Treatment – S1900A 
...................................................................................................................... 
29 
7.5 
Drug Compliance Documentation 
.................................................................................................. 
29 
7.6 
Criteria for Removal from Protocol Treatment 
............................................................................... 
29 
7.7 
Discontinuation of Treatment 
......................................................................................................... 
29 
7.8 
Follow-Up Period 
............................................................................................................................ 
29 
8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS 
.............................................. 
29 
8.1 
NCI Common Terminology Criteria for Adverse Events 
................................................................ 
29 
8.2 
General Considerations ................................................................................................................. 
30 
8.3 
Dose Modifications – Rucaparib .................................................................................................... 
30 
8.4 
Dose Modification Contacts ........................................................................................................... 
32 
8.5 
Adverse Event Reporting 
............................................................................................................... 
32 
9.0 
STUDY CALENDAR 
...................................................................................................................... 
33 
9.1 
Rucaparib 
....................................................................................................................................... 
33 
10.0 CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS 
..................................................... 
36 
10.1 Measurability of Lesions () 
............................................................................................................. 
36 
10.2 Objective Status at Each Disease Evaluation 
................................................................................ 
37 
10.3 Best Response 
............................................................................................................................... 
39 
10.4 Performance Status ....................................................................................................................... 
40 
10.5 Time to Death 
................................................................................................................................. 
40 
10.6 Investigator-Assessed Progression-Free Survival 
......................................................................... 
40 
10.7 Progression-Free Survival by Central Review 
............................................................................... 
40 
10.8 Duration of Response (DoR) 
.......................................................................................................... 
40 
11.0 STATISTICAL CONSIDERATIONS 
.............................................................................................. 
41 
11.1 Sample Size with Power Justification ............................................................................................ 
41 
12.0 DISCIPLINE REVIEW 
.................................................................................................................... 
42 
12.1 Radiology Review .......................................................................................................................... 
42 


 
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13.0 REGISTRATION GUIDELINES 
..................................................................................................... 
43 
13.1 Registration Timing 
........................................................................................................................ 
43 
13.2  Investigator/Site Registration 
......................................................................................................... 
43 
14.0 DATA SUBMISSION SCHEDULE ................................................................................................ 
43 
14.1 Data Submission Requirements .................................................................................................... 
43 
14.2 Master Forms 
................................................................................................................................. 
44 
14.3 Data Submission Procedures ........................................................................................................ 
44 
14.4 Data Submission Overview and Timepoints 
.................................................................................. 
45 
15.0 SPECIAL INSTRUCTIONS............................................................................................................ 
47 
15.1 SWOG Specimen Tracking System (STS) .................................................................................... 
47 
15.2  Translational Medicine and Banking (OPTIONAL FOR PATIENT) 
............................................... 
47 
15.3 LUNGMAP ctDNA Research Assay – ctDNA  bTMB Peripheral Whole Blood (REQUIRED FOR 
PATIENTS prior to treatment initiation) 
..................................................................................... 
49 
15.4 Specimen Flow Diagram 
................................................................................................................ 
51 
15.5 Radiology Review (REQUIRED) 
.................................................................................................... 
52 
16.0 ETHICAL AND REGULATORY CONSIDERATIONS 
................................................................... 
53 
16.1 Adverse Event Reporting Requirements........................................................................................ 
55 
17.0 BIBLIOGRAPHY 
............................................................................................................................ 
61 
18.0 APPENDIX 
..................................................................................................................................... 
63 
18.1 New York Heart Association Classification 
.................................................................................... 
64 
18.2 Monitoring Plan 
.............................................................................................................................. 
65 
18.3 Instructions for the SWOG Biospecimen Bank 
.............................................................................. 
66 
18.4 Investigational Product Incident Report Form 
................................................................................ 
67 
18.5 Examples of Cytochrome (CYP) Substrates 
.................................................................................. 
70 
18.6 Intake Calendar – Rucaparib SWOG Study: S1900A ................................................................... 
71 
18.7  PATIENT DRUG INFORMATION HANDOUT AND WALLET CARD 
............................................ 
75 
 
 
 


 
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CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
CONTACT INFORMATION 
For regulatory requirements: For patient enrollments: 
For data submission: 
Regulatory documentation must 
be submitted to the CTSU via 
the Regulatory Submission 
Portal: 
 
 (Sign in at www.ctsu.org, and 
select the Regulatory > 
Submission.)  
 
Institutions with patients waiting 
that are unable to use the Portal 
should alert the CTSU 
Regulatory Office immediately 
at 1-866-651-2878 to receive 
further instruction and support.   
 
Contact the CTSU Regulatory 
Help Desk at 1-866-651-2878 
for regulatory assistance. 
 
Please refer to the patient 
enrollment section of the protocol 
for instructions on using the 
Oncology Patient Enrollment 
Network (OPEN) is accessed at 
https://www.ctsu.org/OPEN_SYS
TEM/ or https://OPEN.ctsu.org.  
 
Contact the CTSU Help Desk with 
any OPEN-related questions by 
phone or email: 1-888-823-5923, 
or ctsucontact@westat.com.  
Data collection for this study will 
be done exclusively through 
Medidata Rave.  Please see the 
data submission section of the 
protocol for further instructions.  
 
Other Tools and Reports: 
Institutions participating through 
the CTSU continue to have 
access to other tools and reports 
available on the SWOG CRA 
Workbench via the SWOG 
website (www.swog.org).  
  
The most current version of the study protocol and all supporting documents must be downloaded 
from the protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.  
Access to the CTSU members’ website is managed through the Cancer Therapy and Evaluation 
Program - Identity and Access Management (CTEP-IAM) registration system and requires user log in 
with a CTEP-IAM username and password. 
    
For patient eligibility or data submission questions contact the SWOG Statistics and Data 
Management Center (SDMC) by phone or email: 
 
206/652-2267 
LUNGMAPQuestion@crab.org  
 
For treatment or toxicity related questions contact S1900AMedicalquery@swog.org. 
For non-clinical questions (i.e. unrelated to patient eligibility, treatment, or clinical data 
submission) Contact the CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative.  
 
 
 


 
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SCHEMA 
 
 
LUNGMAP/S1400 Registration 
a 
 
 
 
Common Broad Platform CLIA Biomarker Profiling 
b 
 
 
Genomic LOH high and/or deleterious BRCA1/2 mutation by FMI 
c 
 
 
 
S1900A Registration 
 
 
 
   
   
 
Cohort 1   
   
 
Cohort 2 
   
 
           (Squamous)    
      (Non-Squamous) 
 
   
 
            Rucaparib                                     Rucaparib 
 
           Progression 
d                               Progression 
d 
 
a See LUNGMAP Section 5.1 for registration information.  
Note: Patients may have been enrolled on the legacy S1400 screening/pre-screening study. 
 
b Notification of sub-study assignment will be provided by the SWOG Statistics and Data Management 
Center (SDMC) (see LUNGMAP Section 11.0 for details). 
 
c See S1900A Section  5.0 for  the  definition  of LOH  high  and/or  deleterious  BRCA1/2  mutation by 
Foundation Medicine Inc. criteria. 
 
d  Upon progression (as defined in S1900A Section 10.0), patients may be eligible for another sub-study. 
The new sub-study assignment will be determined by the SWOG SDMC (see S1900A Section 14.4). 
 
 


 
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1.0 
OBJECTIVES 
 
1.1 
Primary Objective  
 
a.   
To  evaluate  the  overall  response  rate  (ORR)  (confirmed  and  unconfirmed, 
complete and partial) associated with rucaparib 
in patients with genomic LOH high 
and/or deleterious BRCA1/2 mutations within: 
i. 
Cohort 1: Patients with squamous cell histology  
ii. 
Cohort 2: Patients with non-squamous histology (adenocarcinoma, large 
cell, NSCLC NOS, or mixed histology with any non-squamous component) 
 
1.2 
Secondary Objectives 
 
a. 
To evaluate investigator assessed progression-free survival (IA-PFS) and overall 
survival (OS) associated with rucaparib within each cohort. 
 
b. 
To evaluate duration of response among responders within each cohort. 
 
c. 
To evaluate  the  frequency  and  severity  of  toxicities  associated  with  rucaparib 
among all patients enrolled on the study (combining cohorts). 
 
1.3 
Translational Medicine Objectives 
 
a. 
To evaluate the association between alterations 
in DNA repair genes and response 
by RECIST 1.1. 
 
b. 
To perform comprehensive next-generation sequencing of circulating tumor DNA 
(ctDNA) at baseline 
in all patients to assess 
its clinical utility 
in comparison to tumor 
tissue biomarker profiles. 
 
Note: The proposal to use these specimens would be submitted as an 
amendment to CTEP for approval prior to SDMC review of assay results. 
 
c. 
To establish a tissue/blood repository from patients with refractory non-small cell 
lung cancer (NSCLC). 
 
 
2.0 
BACKGROUND 
 
2.1 
Overview 
 
The  Lung-MAP study is  a  master  protocol  for  genomic  screening  and  multi-sub-study 
testing of drug/biomarker combinations 
in a Phase II/III setting compatible with subsequent 
FDA  approval.    Genomic  screening  of  a  large  patient  resource  provided  by  sites 
participating  in  the  NCI  National  Clinical  Trials  Network  (NCTN)  identifies  a  series  of 
molecular targets/biomarkers which are matched to new drugs, 
leading to appropriate sub-
study assignment and drug treatment.  Each molecular target in Lung-MAP is represented 
by a biomarker for which there 
is an analytically validated diagnostic assay. This approach 
provides the basis for this large-scale screening/clinical registration trial with the ability to 
screen patients, either through genomic analysis or immunohistochemistry based assays, 
with homogeneous eligibility criteria and direct them to a sub-study based on the results of 
screening diagnostic tests.  
 
Based on the results of the tumor analysis, patients will either be assigned to one of the 
biomarker-driven sub-studies or to a ‘non-match’ sub-study for patients with none of the 


 
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eligibility  biomarkers.  The  biomarker-driven  sub-studies  are  designed  around  a 
genotypically-defined  alteration  
in  
the  
tumor  and  a  drug  
that  
targets  
it.  The  non-match 
studies are designed  around  an  
investigational  agent  with  
the  potential  
for  efficacy  
in  a 
broader population. For a full description and justification of the study design, refer to the 
LUNGMAP Screening Protocol. 
 
DNA Damage Repair (DDR) and Synthetic Lethality: 
The viability of the cancer cell is highly dependent on effective maintenance of genomic 
integrity. Since cancer cells are genomically unstable, they are very prone to deleterious 
changes  in  critical  genes  including  those  that  regulate  intracellular  responses  to  DNA 
damage.  DDR  
response  
involves  a  set  of  well-orchestrated  
intracellular  processes  
that 
occur  in  response  to  endogenous  and  exogenous  insults  to  the  cell  genome. (1)The 
specific  nature  of  the  DNA  damage  calls  for  different  DDR  mechanisms  to affect the 
needed  repair.  The  base excision  repair  or  single-strand  break  repair  (BER/SSBR), 
nucleotide excision repair (NER) and mismatch repair (MMR) pathways are responsible for 
the repair of single strand breaks or replication errors. On the other hand, non-homologous 
end-joining (NHEJ) and homologous recombination repair (HRR) are responsible for the 
repair of double strand breaks. The NHEJ results in low-fidelity, error-prone repairs while 
the HRR pathway is the major mechanism for replication-associated double strand breaks 
and  achieves  high  fidelity,  error-free  repair.  Defects  in  DDR  genes  and  or  other  DNA 
damage signaling proteins are commonly encountered 
in sporadic and familial cancers (2). 
Impaired capacity for DNA damage repair as a result of loss of an important element of a 
specific DDR pathway can engender a compensatory activity in some of the other proteins 
involved in the pathway thereby making the cell susceptible to strategies that target this 
compensating  protein.  Additionally,  there  may  be  an  overdependence  of  the  cell  on 
alternative repair pathways distinct from the pathway impaired by the genetic alteration. A 
classic example of this biological derangement is the impairment of the HRR pathway in 
patients  with  BRCA1  or  BRCA2  mutation leading  
to  
inability  of  
the  cell  
to  
repair  double 
strand breaks. Such patients are vulnerable to inhibitors of poly (ADP) ribose polymerase 
(PARP) enzyme because the inactivation of the BER pathway by the PARP inhibitor leads 
to persistence and progression of single strand breaks to the lethal double strand breaks. 
The 
inability of the cells to repair double strand breaks as a consequence of 
impaired HRR 
caused  by  
the  BRCA  mutation  results  
in  cell  death.  This  
therapeutic  construct  
is  aptly 
referred to as synthetic lethality and was initially demonstrated using BRCA-deficient cell 
lines  leading  to  clinical  evaluation  of  PARP  inhibitors  in  ovarian  and  breast  cancer 
harboring  deleterious  mutations  
in  
the  BRCA  genes. It  
is  now  recognized  
that  besides 
BRCA1 and BRCA2, synthetic lethality can also be induced when genetic mutations affect 
other  critical  components  of  HRR.  In  addition  to  these  mutations,  genomic  loss  of 
heterozygosity  
(LOH)  has  been  shown  
to  be  a  phenotypic  biomarker  
to  
identify  ovarian 
cancer patients with impaired DDR. In advanced ovarian cancer, rucaparib demonstrated 
clinical benefit (increased ORR and prolonged PFS) in LOH high tumors, even if tumors 
were BRCA wild-type with compared to LOH low ovarian cancers. (3) S1900A seeks to 
examine  whether BRCA-positive  or  LOH  high  NSCLC  also  derives  clinical  benefit  
from 
rucaparib.  
 
Summary of Biomarker Approach in S1900A 
 
On April 6, 2018, the FDA approved rucaparib for the maintenance treatment of recurrent 
epithelial  ovarian,  
fallopian  
tube,  or  primary  peritoneal  cancer  who  are  
in  a  complete  or 
partial response to platinum-based chemotherapy. In addition  
to  mutations in BRCA1/2, 
genomic  LOH  has  been  shown  
to  be  a  phenotypic  biomarker  
to  
identify  ovarian  cancer 
patients treated with two or more chemotherapies who are likely to respond to rucaparib. 
 
The   FDA   also   concurrently   approved  the   complementary   diagnostic  test, 
FoundationFocusTM CDx BRCA LOH, for tumor samples to determine HRD status. 
 


 
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Patients  with  deleterious  BRCA1/2  mutations  and/or  LOH  high  NSCLC  detected  on  
the 
Foundation Medicine assay employed 
in Lung-MAP will be eligible for this study. In addition 
to breast and ovarian cancer, PARP inhibitors have demonstrated activity across multiple 
tumor types harboring deleterious mutations 
in BRCA1/2 such as: breast, ovarian, prostate 
and pancreatic adenocarcinoma. (4,5)   
 
LOH high tumors are also included as a phenotypic biomarker of HRD. The computational 
algorithm for genome-wide LOH used in the Foundation One assay for this sub-study is 
identical to the FDA approved complementary diagnostic test FoundationFocus CDx BRCA 
LOH for ovarian cancer. For ovarian cancer LOH ≥ 16% is considered high. In this Lung-
MAP sub-study for NSCLC a higher cutpoint of ≥ 21% is used to enrich for patients most 
likely to benefit from PARP inhibition (Figure 1). 
 
Additional  genomic  aberrations  in  DNA  repair  proteins  detected  on  the  Foundation 
Medicine  next-generation  sequencing  assay  will  be  examined  on  an  exploratory  basis. 
Tissue and blood will be banked providing the ability for future exploratory analysis. 
 
Prevalence of BRCA-positive in Lung Cancer: 
In  squamous  histology  patients  screened  on  Lung-MAP  the  prevalence  of  deleterious 
BRCA1/2  mutations  
is  5.8%.  Analysis  of  
lung  adenocarcinoma  patients  
in  The Cancer 
Genome Atlas (TCGA) indicates 1.4% of patients harbor a deleterious BRCA1/2 mutation. 
 
Prevalence of LOH in Lung Cancer: 
The  frequency  of  deleterious  alterations  (deletions  and  mutations  and  copy  number 
variations)  
in  NSCLC  has  been  analyzed  
in  
the  TCGA.  Approximately  25%  of  cases  of 
squamous lung cancer and 9% of adenocarcinoma had LOH ≥ 21% based on TCGA data. 
Genomic LOH is a biomarker for DNA-damage that has been shown to confer sensitivity 
to PARP inhibitors, and can be derived computationally using the existing SNPs on any of 
Foundation  Medicine’s  
tissue-based  NGS  assays  using  
the  ~3500  SNPs  on  
the  panel. 
Examining  NSCLC cases from Foundation  Medicine,  
lung adenocarcinoma  LOH ≥ 21% 
was found in approximately 16% in squamous cell lung cancer and likely comparable to 
TCGA  data  in  lung  adenocarcinoma.  Based  on  data  examining  clinical  outcomes  of 
patients with LOH high advanced ovarian cancer treated with rucaparib, we expect LOH 
high NSCLC will be susceptible to the synthetic lethal effect of rucaparib therapy and will 
be appropriate for targeted therapy using a PARP inhibitor.  


 
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Platinum Sensitivity in Lung Cancer: 
The  objective  response  to  platinum-based  frontline  chemotherapy  and  the  duration  of 
benefit are strongly correlated. These endpoints are also well-established surrogates for 
further  benefit  
from  salvage  
therapy  and  overall  patient  outcome  
in  ovarian  cancer and 
SCLC. (6, 7, 8) Additionally, platinum sensitivity shows significant association with clinical 
benefit of PARP inhibitors in ovarian cancer and in SCLC patients. (9, 10) Retrospective 
and  single  institution  studies  suggested  that  patients  with  platinum-sensitive  NSCLC 
achieved  better  outcome  with  salvage  
targeted  
therapy. (11) In  squamous  
lung  cancer 
patients  
from  
the  TCGA  dataset,  genomic  LOH  ≥  21%  was  associated  with  an  overall 
survival (OS) benefit to platinum-based chemotherapy (HR=0.295; p=0.023).  
 
Study Design: 
There is limited clinical exploration of single agent PARP inhibitor therapy in lung cancer. 
The  proposed  sub-study  of  
rucaparib  will  be  
the  
first  prospective  study  
to  evaluate  
the 
clinical benefit of a PARP inhibitor as a single agent in patients with non-squamous lung 
cancer 
in addition to squamous cell 
lung cancer. It 
is also the first prospective study 
in 
lung 
cancer  to  use  loss  of  heterozygosity  (LOH)  as  a  selection  biomarker.  Patients  with 
susceptible  tumors  defined  as  LOH  ≥  21%  using  the  ~3500  SNPs  on  the  Foundation 
Medicine panel will be identified as part of the screening conducted under the Lung-MAP 
protocol, 
in addition to those harboring a BRCA1 or BRCA2 mutation. Two cohorts stratified 
by histology (squamous and non-squamous) will accrue patients with LOH high NSCLC. 
Rucaparib will be administered orally with each cycle comprising 21 continuous days. 
 
2.2 
Rationale 
 
New  treatments  for  advanced  NSCLC  with  progressive  disease  after  chemotherapy, 
immune  checkpoint  blockade,  or  appropriate  targeted  therapies  for  oncogene  driven 
subsets of NSCLC remains an acute area of unmet need. The PARP inhibitor rucaparib 
was  granted  accelerated  approval  by  the  FDA  
in  December  2016  for  the  treatment  of 
patients  with  deleterious  BRCA  mutation  (germline  and/or  somatic)  advanced  ovarian 
 
 
Figure 1: Genomic LOH ≥ 21% in the TCGA by Histology. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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cancer. On April 6, 2018, the FDA also approved rucaparib for the maintenance treatment 
of  
recurrent  epithelial  ovarian,  
fallopian  
tube,  or  primary  peritoneal  cancer  who  are  
in  a 
complete or partial response to platinum-based chemotherapy. In addition to mutations in 
BRCA1/2, genomic LOH has been shown to be a phenotypic biomarker to identify ovarian 
cancer patients  
treated  with  
two  or  more  chemotherapies  who  are  
likely  
to  respond  
to 
rucaparib. (12) 
 
The   FDA   also   concurrently   approved  the   complementary   diagnostic  test, 
FoundationFocusTM CDx BRCA LOH, for tumor samples to determine HRD status. 
 
This trial seeks to demonstrate whether LOH high and/or deleterious BRCA1/2 mutations, 
phenotypic biomarkers that has been shown to confer sensitivity to rucaparib in ovarian 
cancer,  also  confers  sensitivity  in  NSCLC  patients.  Exploring  rucaparib  activity  in 
adenocarcinoma and squamous NSCLC with a genomic LOH ≥ 21% will provide a robust 
evaluation of rucaparib in patients most likely to respond in both histologies.  
 
In  addition,  the  detection  rates  of  mutations  observed  in  ctDNA  isolated  from  patient 
plasma at baseline will be evaluated in comparison to mutations observed in tumor tissue.  
It is expected that mutations identified in plasma will be synonymous with those detected 
in tissue, with the following exceptions: a subset of patients may have insufficient amounts 
of ctDNA 
in circulation for detection, and secondly, a subset of patients may have additional 
mutations detected in plasma that are associated with metastases and not present in the 
original  tissue  biopsy.    The  overarching  goal  of  the  Lung-MAP  liquid  biopsy  program, 
planned  across  multiple  sub-studies,  is  to  assess  whether  positive  identification  of 
mutations 
in ctDNA can be utilized for molecular assignment.  In this sub-study, the primary 
objective is to correlate detection frequencies between tissue and plasma. 
 
If the requisite number of objective responses is observed, this is a signal to move forward 
to  
larger,  randomized  later  stage  trials  
in  both  the  treatment  and  maintenance  setting 
following platinum-based chemotherapy. A positive study would support genomic LOH as 
a  biomarker  
for  
rucaparib  and  PARP  
inhibitor  drug  development  
in  NSCLC,  whereas  a 
negative study would show a lack of benefit of rucaparib in NSCLC. 
 
2.3 
Data 
 
Rucaparib has been evaluated in Phase 1 and 2 clinical studies and is being evaluated in 
ongoing Phase 2 and Phase 3 clinical studies.  The oral formulation as monotherapy 
is the 
focus of current development efforts. 
 
An overview of data from nonclinical and clinical studies of rucaparib are provided below 
and  described  
in  detail  
in  
the  
rucaparib  
Investigator’s  Brochure  
(IB).  A  summary  of  
the 
benefit: risk is also provided in the rucaparib IB. 
 
In  Part  1  of  the  ARIEL2  study,  patients  with  recurrent,  platinum-sensitive,  high-grade 
ovarian carcinoma were classified 
into one of three predefined homologous recombination 
deficiency subgroups on the basis of tumor mutational analysis: BRCA mutant (deleterious 
germline  or  somatic),  BRCA  wild-type  and  LOH  high,  or  BRCA  wild-type and LOH low.  
Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 21-
day cycles until disease progression or any other reason for discontinuation.  The primary 
endpoint was progression-free survival (PFS). PFS was significantly longer in the BRCA 
mutant (hazard ratio 0.27, 95% CI 0.16-0.44, p<0.0001) and LOH high (0.62, 0.42-0.90, 
p=0.011) subgroups compared  with the  LOH  
low subgroup.   Additionally,  more  patients 
achieved  confirmed  RECIST  responses,  achieved  confirmed  RECIST  and  CA-125 
responses, and had longer response durations in the LOH high subgroup than in the LOH 
low subgroup. For example, the ORR was 29% (95% CI 20-40) and 10% (95% CI 4-20) in 
BRCA wild-type LOH high and low subgroups, respectively. (13) 


 
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In the ARIEL3 trial that randomized patients with ovarian cancer to receive either rucaparib 
or placebo as maintenance therapy following response to platinum-based chemotherapy, 
genomic LOH was used to select potentially select BRCA wild-type patients for improved 
clinical  outcomes  to  rucaparib.  In  these  patients,  the  PFS  was  increased  in  rucaparib 
patients as compared to placebo for both the LOH high patients (median PFS 9.7 vs. 5.4 
months; HR=0.44, P<0.0001) and LOH low patients (median PFS 6.7 vs. 5.4 months; HR 
0.58, p=0.005) (Figure 2).  In summary, improved clinical outcomes have been observed 
in  LOH  high  ovarian  cancer  patients  administered  rucaparib  in  both  treatment  and 
maintenance settings. (14) 
 
 
 
 
A summary of the clinical experience with rucaparib is provided below. 
 
Completed Studies  
 
• A4991002: A Phase 1 open-label, dose-escalation study of IV rucaparib 
in combination 
with temozolomide (TMZ) in patients with advanced solid tumors (Part 1) or malignant 
melanoma (Part 2) (15) 
• A4991005:  A Phase 2, open-label study of IV rucaparib in combination with TMZ in 
patients with metastatic melanoma. (16) 
• A4991014:  A Phase  1,  open-label,  dose-escalation  study  of  IV  and  oral  rucaparib 
administered with different chemotherapeutic agents 
in patients with an advanced solid 
tumor. (17) 
• CO-338-023 (RUCAPANC): A Phase 2, single-arm, open-label study of monotherapy 
oral  rucaparib  as  
treatment  
for  patients  with  previously  
treated  
locally  advanced  or 
metastatic  pancreatic  ductal  adenocarcinoma  and  a  known  deleterious  BRCA 
mutation.  
 
 
Figure 2: ARIEL 3 Trial: Investigator assessed PFS in BRCA Wild-Type Advanced Ovarian Cancer Patients 


 
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Ongoing Studies 
 
• CO-338-010: 3-part, open-label, Phase 1/2 study of monotherapy oral rucaparib. (18)  
o Part  1: Phase  1  portion  evaluating  PK  and  safety  of  escalating  doses  of 
rucaparib 
in patients with solid tumors; this portion 
identified 600 mg twice daily 
(BID) as the recommended starting dose for future studies (n = 56; completed). 
o Part  2:  A Phase  2  portion  evaluating  
the  efficacy  and  safety  of  
rucaparib  
in 
patients  with  relapsed,  high-grade  ovarian  cancer  associated  with  a  BRCA 
mutation.  
o Part 3: A Phase 2 portion in patients with a relapsed solid tumor associated 
with a BRCA mutation in order to characterize the PK, food effect, and safety 
profile of a higher dose strength tablet (n = 26; enrollment complete). 
• CO-338-017  (ARIEL2):  A  2-part  open-label  Phase  2  study  of  monotherapy  oral 
rucaparib for treatment of relapsed, high-grade ovarian cancer patients. Patients will 
be  classified  into  molecularly-defined  subgroups,  including  tumor  BRCA  (tBRCA, 
inclusive  of  both  germline  and  somatic  BRCA)  and  BRCA-like,  by  a  prospectively 
defined genomic signature. (19) 
• CO-338-014  
(ARIEL3):  A Phase  3,  
randomized,  double-blind study  of  monotherapy 
oral  rucaparib  versus  placebo  as  switch  maintenance  treatment  in  patients  with 
platinum-sensitive-, relapsed, high-grade ovarian cancer who achieved a response to 
platinum-based chemotherapy. (20) 
• CO-338-044  (DDI  study):  A  2-part,  Phase  1,  open-label,  multiple-probe  drug-drug 
interaction (DDI) study. 
• CO-338-043 [ARIEL4] is evaluating rucaparib versus chemotherapy as treatment for 
patients  with  relapsed  high-grade  ovarian  cancer  associated  with  a  deleterious 
BRCA1/2 mutation 
• CO-338-045 is an open-label Phase 1, single-dose study of the disposition of [14C]-
radiolabel rucaparib in patients with advanced solid tumors. 
• CO-338-052 [TRITON2] is a Phase 2 study evaluating rucaparib efficacy in mCRPC 
whose tumors are associated with HRD by enrolling mCRPC patients with mutations 
in BRCA1/2, ATM, or other HR genes.  
• CO-338-063 [TRITON3] is a Phase 3, randomized, 2-arm study evaluating rucaparib 
vs. physician’s choice (abiraterone acetate, enzalutamide or docetaxel) 
in patients with 
mCRPC associated with a deleterious BRCA1/2 or ATM mutation. 
• CO-338-078  is  a  Phase  1,  open-label,  parallel  group  study  to  determine  the 
pharmacokinetics,  safety,  and  
tolerability  of  
rucaparib  
in  patients  with  an  advanced 
solid tumor and either moderate hepatic impairment or normal hepatic function. 
• CO-338-085  [ATLAS]  is  a  Phase  2,  open-label  study  evaluating  rucaparib  for  the 
treatment of patients with locally advanced or metastatic urothelial cancer. 
 
Overview of Pharmacokinetics (PK) 
 
Nonclinical  studies:  Rucaparib  demonstrated  species-dependent  oral  bioavailability, 
moderate plasma protein binding, and large volumes of distribution in nonclinical species. 
As  a  P-glycoprotein  (P-gp)  and  breast  cancer  resistance  protein  (BCRP) substrate, 
rucaparib demonstrated minimal penetration of rucaparib-derived radioactivity through the 
blood-brain barrier. In vitro data suggested slow metabolism by cytochrome P450 (CYP) 
enzymes, with CYP2D6 and to a lesser extent CYP1A2 and CYP3A4 contributing to the 
metabolism of rucaparib. Rucaparib was mainly excreted in feces in rats and dogs after 
oral dosing. 
In vitro, rucaparib reversibly inhibited CYP1A2, CYP2C9, CYP2C19, and CYP3A, and to a 
lesser extent CYP2C8, CYP2D6, and uridine diphosphate (UDP)-glucuronosyltransferase 
(UGT)  1A1  (UGT1A1).  Rucaparib  
induced  CYP1A2,  and  down-regulated  CYP2B6  and 
CYP3A4  
in  human  hepatocytes  at  clinically  relevant  exposures.  Rucaparib  
is  a  potent 


 
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inhibitor of multidrug and toxin extrusion 1 (MATE1) and MATE2-K, a moderate 
inhibitor of 
organic cationic transporter 1 (OCT1) and may inhibit P-gp and BCRP in the gut.  
 
Clinical studies: Assessment of rucaparib PK in cancer patients showed an approximate 
dose-proportional  exposure  after  once  daily  (QD)  or  BID  dosing,  rapid  absorption  with 
maximum plasma concentration (Cmax) achieved within 1.5 to 6 hours, and distribution into 
tissue.  The  oral  bioavailability  was  36%  and  
terminal  half-life  
(T
1/2)  
ranged  
from  9.23  
to 
33.6 hours. Rucaparib was moderately bound to human plasma proteins in vitro. 
At a dose of 600 mg BID rucaparib, steady-state was achieved after approximately 1 week. 
At the target clinical dose of 600 mg, a high-fat meal increased the C
max and area under 
the plasma concentration-time curve from 0 to  24 hours (AUC
0-24h) of rucaparib  by 20% 
and  38%,  respectively,  and  delayed  the  median  time  to  occurrence  of  Cmax (T
max)  by 
approximately 2.5 hours as compared with these parameters under fasted conditions. The 
effect of food on rucaparib PK is not considered to be clinically significant, thus rucaparib 
can be taken with or without food. 
In  a  preliminary  assessment  of  rucaparib  metabolism  in  patients,  rucaparib 
biotransformation  pathways  included  hydroxylation  or  oxidation,  N-demethylation, 
deamination, and phase II methylation. A carboxylic acid metabolite (M324) and a phase 
II N-methylated metabolite of M324 (M338) were identified as major metabolites.  
Drug 
interactions with rucaparib as a substrate were assessed 
in a population PK analysis. 
CYP2D6 phenotypes (poor metabolizers, intermediate metabolizers, normal metabolizers, 
and  ultra-rapid  metabolizers)  and  CYP1A2  phenotypes  (normal  metabolizers  and 
hyperinducers) did not significantly impact the steady-state exposure of rucaparib at 600 
mg  BID.  Current  smokers  had  overlapping  rucaparib  exposures  as  compared  to 
nonsmokers  and  former  smokers.  Collectively,  the  results  suggest that  CYP1A2  and 
CYP2D6  play  a  limited  role  in  rucaparib  metabolism  in  vivo,  and  no  rucaparib  dose 
adjustment is needed when concomitantly administered with CYP inhibitors. 
Concomitant treatment with proton pump inhibitors (PPIs) showed no clinically significant 
effect on rucaparib PK. No dose modification of rucaparib is required for patients who are 
receiving concomitant treatment with a PPI. 
Results  from  Study  CO-338-044  evaluating  potential  drug-drug  interactions  (DDI)  with 
rucaparib, indicated that rucaparib, at 600 mg BID, moderately inhibited CYP1A2, weakly 
inhibited CYP2C9, CYP2C19, and CYP3A, and showed no clinically significant effect on 
P-gp.  
 
Overview of Efficacy  
 
Efficacy analysis was based on pooled efficacy data from 106 patients with BRCA mutant 
ovarian cancer, who received two or more prior chemotherapy regimens, and who initiated 
treatment with rucaparib at 600 mg BID in Part 2A of Study CO-338-010 and Parts 1 and 
2 of Study CO-338-017.  
 
Efficacy data indicate that many patients with advanced ovarian cancer associated with a 
BRCA1/2 gene mutation and who had two or more prior therapies achieve RECIST and/or 
GCIG  cancer  antigen  125  (CA125)  responses.  The  confirmed  objective  response  rate 
(ORR) per RECIST by 
investigator review was 53.8% (57/106) and the confirmed response 
by  RECIST  or  GCIC  CA-125  was  70.8%  
(75/106).  The  confirmed  ORR  per  RECIST  by 
independent review was 41.5% (44/106).  
 
In addition, BRCA wild-type, LOH high patients with relapsed, platinum sensitive ovarian 
cancer  were  also  shown  
to  derive  benefit  
from  rucaparib,  with  44%  achieving  RECIST 
and/or GCIG CA-125 responses (ARIEL2, Part 1).  
 


 
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Overview of Safety  
 
The US prescribing information (USPI) for rucaparib in the treatment setting is based on 
377  patients  with  advanced  ovarian  cancer.  The  most  common  treatment-emergent 
adverse  events  (TEAEs)  were  nausea,  asthenia/fatigue,  vomiting,  anemia/hemoglobin 
decreased, alanine aminotransferase (ALT)/aspartate aminotransferase (AST) increased, 
constipation, decreased appetite, and dysgeusia. (21) Commonly experienced Grade 3 or 
higher  TEAEs  included  anemia/hemoglobin  decreased,  asthenia/fatigue,  and  ALT/AST 
increased. 
 
Integrated Safety Analysis:  
Results  of  a  more  
recent  
integrated  safety  analysis  
for  
rucaparib  
treatment  
in  over  900 
patients with ovarian cancer who received 600 mg BID rucaparib in either the treatment or 
maintenance setting showed that the most common TEAEs reported were primarily mild to 
moderate (Grade 1-2) 
in severity and 
included gastrointestinal disorders (nausea, vomiting, 
diarrhea,  constipation,  and  abdominal  pain),  asthenia/fatigue,  anemia/decreased 
hemoglobin, ALT/AST increased, decreased appetite, and dysgeusia. The most common 
TEAEs  ≥  Grade  3  included  anemia/decreased  hemoglobin,  ALT/AST  increased, 
neutropenia/decreased absolute neutrophil count (ANC), and asthenia/fatigue. 
 
The laboratory abnormalities were consistent with the TEAEs, with decreased hemoglobin 
(and  associated  increase  in  mean  corpuscular  volume  [MCV]  and  mean  corpuscular 
hemoglobin [MCH]), 
increased ALT, 
increased AST, and 
increased serum creatinine, most 
commonly  occurring.  Decreased  platelets,  neutrophils,  leukocytes,  lymphocytes,  and 
increased  cholesterol  were  observed  to  a  lesser  extent.  The  transient  elevations  in 
ALT/AST with rucaparib treatment 
in either the treatment or maintenance settings were not 
associated  with  abnormal  increases  in  bilirubin  or  other  criteria  for  drug-induced 
hepatotoxicity  and  generally  resolved  over  time.  Furthermore,  no  cases  met  Hy’s  law 
criteria for drug-induced liver injury (DILI) and few patients discontinued rucaparib due to 
ALT/AST  elevations. (22, 23) Similarly,  elevations  in  creatinine  were  self-limiting  and 
stabilized  over  time.  Elevated  serum  creatinine  levels  resolved  upon  interruption  or 
discontinuation  of  
rucaparib,  were  not  accompanied  by  changes  
in  blood  urea  nitrogen 
(BUN),  and  did  not  lead  to  discontinuation  of  rucaparib  treatment. (24, 25) Increased 
creatinine  with  rucaparib  
treatment  
is  
likely  due  
to  
the  potent  
inhibition  by  rucaparib  of 
MATE1 and MATE2-K renal transporters. Effects on cardiac channel activity in vitro and a 
comprehensive  assessment  of  the  effects  of  rucaparib  on  electrocardiogram  (ECG) 
parameters in cancer patients demonstrated a low risk of cardiac effects by rucaparib. 
 
Adverse Events of Special Interest: 
Myelodysplastic  syndrome  (MDS)  and  acute  myeloid  leukemia  (AML)  are  considered 
adverse events of special 
interest (AESIs), as these events have been observed 
in patients 
exposed to cytotoxic chemotherapy (eg, platinum and anthracyclines) used for treatment 
of ovarian cancer as well as with PARP 
inhibitors, 
including rucaparib. Patients 
in rucaparib 
clinical  studies  diagnosed  with  MDS  or  AML  had  significant  confounding  risk  factors 
including prior cytotoxic chemotherapy, as well as a deleterious BRCA mutation. (26, 27) 
Based  on these confounding factors, there is insufficient scientific evidence to conclude 
that  MDS  and  AML  are  causally  related  to  rucaparib.  More  information  on  AESIs  for 
rucaparib is provided in the rucaparib IB. 
 
2.4 
Feasibility 
 
This  trial  will  be  open  to  patients  with  NSCLC  regardless  of  histology  (non-squamous 
(predominantly adenocarcinoma) or squamous cell carcinoma) who enroll on Lung-MAP 
with deleterious BRCA1/2 mutation and/or LOH high tumors and progression either on or 
after platinum-based chemotherapy or PD-1/PD-L1 antibodies. Analysis of the TCGA and 
Foundation  Medicine  databases  suggests  that  tumors  with  a  LOH  ≥  21%  comprise 


 
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approximately 16% of squamous cell 
lung cancer and 9% 
lung adenocarcinoma. Based on 
TCGA, 1.4% BRCA 1/2 
is common 
in NSCLC. We note that the S1400G sub-study of Lung-
MAP  
is a Phase 2 trial  of the  PARP inhibitor talazoparib  
in homologous repair deficient 
(HRD) squamous cell lung cancer. Based on the TCGA, there is only 4% overlap for LOH 
high squamous NSCLC and the talazoparib HRRD gene list for S1400G sub-study (Figure 
3). Similar frequency of overlap was observed in the Foundation Medicine NGS screening 
data in sqNSCLC from the Lung-MAP program. Patients that overlap will be randomized 
to either S1400G (talazoparib) or S1900A (rucaparib) sub-studies. Notably, patients with 
adenocarcinoma are excluded from S1400G, thus there is no overlap in adenocarcinoma 
patients between the rucaparib and S1400G talazoparib sub-study. In summary, with the 
expected frequency of LOH-positive squamous and adenocarcinoma tumors, we expect 
robust accrual for this Lung-MAP sub-study as outlined in our accrual estimates. 
 
2.5 
Inclusion of Women and Minorities and Planned Enrollment Report 
 
This study was designed to 
include women and minorities but was not designed to measure 
differences of intervention effects.  The anticipated accrual in the ethnicity/race and sex 
categories is shown in the table below.  
 
DOMESTIC PLANNED ENROLLMENT REPORT 
Racial 
Categories 
Ethnic Categories 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
American Indian/ 
Alaska Native 
0 
0 
0 
0 
0 
Asian 
1 
2 
0 
0 
3 
Native Hawaiian 
or Other Pacific 
Islander 
0 
0 
0 
0 
0 
Black or African 
American 
2 
5 
0 
0 
7 
White 
34 
41 
1 
2 
78 
More Than One 
Race 
0 
0 
0 
0 
0 
Total 
37 
48 
1 
2 
88 
 
 
3.0 
DRUG INFORMATION 
 
Investigator Brochures  
 
For information regarding Investigator Brochures, please refer to SWOG Policy 15. 
 
For this sub-study, rucaparib 
is investigational and is 
being provided under an IND held by SWOG.  
For INDs filed by SWOG, the protocol serves as the Investigator Brochure for the performance of 
the protocol.  In such instances, submission of the protocol to the IRB should suffice for providing 
the IRB with information about the drug.  However, in cases where the IRB insists on having the 
official Investigator Brochure from the company, requests may be submitted to the CTSU website 
by completing the CTSU Request for Clinical Brochure Form under the sub-study’s abstract page 
> Documents > Pharmacy Tab.  
 
 


 
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3.1 
Rucaparib (Rubraca ®) (NSC 804038) (IND-143217) 
 
a. 
PHARMACOLOGY 
 
Mechanism  of  Action:  Rucaparib  is  a  potent  small  molecule  inhibitor  of  poly-
adenosine  diphosphate  (ADP)  ribose  polymerase  (PARP)  enzymes,  including 
PARP-1,  PARP-2,  and PARP-3. Rucaparib  also  prevents  the  dissociation  of 
PARP-1 and PARP-2 enzymes from damaged DNA (“PARP trapping”). Inhibition 
of PARP enzymatic activity and 
increased formation of PARP-DNA complexes can 
result in increased DNA damage, cytotoxicity, and apoptosis. 
 
b. 
PHARMACOKINETICS 
1. 
Absorption:  The  median  Tmax was  1.9  hours  at  the  approved 
recommended  dose.  The  mean  absolute  bioavailability  of  rucaparib 
immediate-release  tablet  was  36%  with  a  range  from  30%  to  45%. 
Following a high-fat meal, the Cmax was increased by 20% and AUC0-
24h was  increased  by  38%,  and  Tmax  was  delayed  by  2.5  hours,  as 
compared to dosing under fasted conditions. The effects of food were not 
deemed to be clinically significant; rucaparib may be administered with or 
without food. 
2. 
Distribution: Rucaparib had a steady-state volume of distribution of 113 L 
to 262 L following a single intravenous dose of 12 mg to 40 mg rucaparib. 
In  vitro,  
the  protein  binding  of  rucaparib  was  70%  
in  human  plasma  at 
therapeutic  concentrations.  Rucaparib  preferentially  distributed  to  red 
blood cells with a blood-to-plasma concentration ratio of 1.83. 
3. 
Metabolism: In vitro, rucaparib had a low metabolic turnover rate and was 
metabolized primarily by CYP2D6, and to a lesser extent by CYP1A2 and 
CYP3A4.  Based  on  population  pharmacokinetic  analyses,  steady-state 
concentrations  following  rucaparib  600  mg  twice  daily  did  not  differ 
significantly across CYP2D6 or CYP1A2 genotype subgroups. 
4. 
Elimination:  The  mean  terminal  T1/2  of  rucaparib  was  25.9  hours, 
following a single oral dose of 600 mg rucaparib. The apparent clearance 
ranged  
from  15.3  
to  79.2  L/hour,  
following  
rucaparib  600  mg  oral  
twice 
daily. 
c. 
ADVERSE EFFECTS 
 
1. 
Adverse Effects:  
(Version: November 2, 2020) 
Adverse Events with Possible Relationship  
to rucaparib 
Likely 
(> 20%) 
Less Likely 
(4 ≤ 20%) 
Rare but Serious (≤ 
3%) 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
Anemia/decreased 
hemoglobin 
Neutropenia/Neutrophi
l count decreased 
 
Thrombocytopenia/ 
decreased platelets  
 
 
GASTROINTESTINAL DISORDERS 
Abdominal pain 
Abdominal distension  
Constipation 
Dyspepsia 
 


 
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Adverse Events with Possible Relationship  
to rucaparib 
Likely 
(> 20%) 
Less Likely 
(4 ≤ 20%) 
Rare but Serious (≤ 
3%) 
Diarrhea 
Dry mouth 
 
Nausea 
Gastroesophageal 
reflux disease 
 
Vomiting 
Stomatitis 
 
GENERAL DISORDERS 
Asthenia/fatigue 
Mucosal inflammation  
 
Edema peripheral 
 
 
Pyrexia 
 
INFECTIONS AND INFESTATIONS 
 
Nasopharyngitis  
 
 
Upper respiratory tract 
infection 
 
 
Urinary tract infection 
 
INVESTIGATIONS 
ALT/AST increased 
Blood creatinine 
increased 
 
 
 Blood alkaline 
phosphatase 
increased 
 
 
 Blood cholesterol 
increased 
 
METABOLISM AND NUTRITION DISORDERS 
Decreased appetite 
Dehydration  
 
 
Hypokalemia  
 
 
Hypercholesterolaemi
a 
 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
 
Arthralgia 
 
 
Back pain 
 
 
Musculoskeletal pain   
 
Pain in extremity 
 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED 
 
 
Myelodysplastic 
Syndrome 
 
 
Acute Myeloid 
Leukemia 
NERVOUS SYSTEM DISORDERS 
Dysgeusia 
Dizziness 
 
 
Headache 
 
PSYCHIATRIC DISCORDERS 
 
Anxiety 
 
 
Depression 
 
 
Insomnia 
 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
 
Cough 
Pneumonitis 
 
Dyspnea 
 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
 
Alopecia 
 
 
Dry skin 
 


 
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Adverse Events with Possible Relationship  
to rucaparib 
Likely 
(> 20%) 
Less Likely 
(4 ≤ 20%) 
Rare but Serious (≤ 
3%) 
 
Erythema  
 
 
Photosensitivity 
reaction 
 
 
Pruritus  
 
 
Rash 
 
VASCULAR DISORDERS 
 
Hot flush 
 
 
Hypertension 
 
 
Adverse events occurring in < 1%, postmarketing, and/or case reports:  
 
MDS/AML: A review of all reports of myelodysplastic syndrome (MDS) and 
acute  myeloid  
leukemia  (AML)  
that  have  occurred  
in  
the  entire  clinical 
development program up to 27 June 2020 revealed a total of 25 reports in 
patients  exposed  to  rucaparib.  Nearly  every  patient  who  developed 
MDS/AML  reported  having  experienced  multiple/persistent  cytopenias 
prior to the diagnosis of MDS/AML. Events of  MDS  and AML have  also 
been reported with other PARP  
inhibitors although the etiology of these 
events 
is confounded by prior treatments and the relationship to rucaparib 
is not clear. 
 
Pneumonitis:  Cases  of  pneumonitis  have  been  reported  in  patients 
receiving PARP  
inhibitor treatment. There have  been 10 serious clinical 
study  cases  and  7  non-serious  clinical  study  cases  reported.  Among 
patients  receiving  rucaparib,  pneumonitis  has  been  reported  in 
approximately  0.1%  of  patients.  There  is  not  a  clear  mechanistic  link 
between pneumonitis and PARP inhibitor treatment.  
 
For additional information on reporting adverse events of special interest, 
see Section 16.1f. 
 
2. 
Pregnancy  and  Lactation: Based  on  the  finding  that  rucaparib  was 
embryotoxic  at  all  doses  administered  
in  
the  embryo-fetal  development 
study and the potential of PARP inhibitors to affect spermatogenesis, it is 
advised that female and male patients of reproductive potential and their 
opposite sex partners of reproductive potential practice a highly effective 
method  of  contraception  during  and  after  treatment  with  rucaparib  as 
specified per protocol. Female patients of childbearing potential and their 
male  partners  are  advised  to  practice  a  highly  effective  method  of 
contraception during treatment with rucaparib and for 6 months following 
the 
last dose of rucaparib. Male patients of reproductive potential and their 
female partners of childbearing potential are advised to practice a highly 
effective method of contraception during treatment with rucaparib and for 
a minimum of 3 months following the last dose of rucaparib. Male patients 
must  not  make  sperm  donations  during  treatment  and  for 3 months 
following the last dose of rucaparib. 
 
3. 
Drug Interactions:  
 
Rucaparib  
is  a  moderate  
inhibitor  of  CYP1A2,  and  a  weak  
inhibitor  of 
CYP2C9,  CYP2C19,  and  CYP3A.  Concomitant  administration  of 


 
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rucaparib with CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates may 
alter  the  pharmacokinetic  or  pharmacodynamics  properties  of  these 
concurrent medications. In vitro, rucaparib had a low metabolic turnover 
rate and was metabolized primarily by CYP2D6 and to a lesser extent by 
CYP1A2  and  CYP3A4.  Caution  should  be  used  
for  concomitant  use  of 
strong  inhibitors  or  inducers  of  these  liver  enzymes.  Rucaparib  is  a 
substrate of transporter P-gp and BCRP, a potent inhibitor of MATE1 and 
MATE2-K, a moderate inhibitor of OCT1, and a weak inhibitor of OCT2. 
Cautions  should  be  taken  for  concomitant  use  with  substrates  and 
inhibitors of these transporters. See Section 7.2 for details. 
 
d. 
DOSING & ADMINISTRATION 
See Section 7.0 Treatment Plan. 
 
e. 
HOW SUPPLIED 
 
1. 
Rucaparib 200mg,  250mg,  and  300mg immediate-release  film-coated 
tablets will be supplied by Clovis and distributed by NCI Pharmaceutical 
Management Branch in the US. 
 
The  physical  appearances  of  
the  
tablets  are  unique  
in  order  
to  ensure 
proper identification. The 200 mg tablets are blue, round (11 mm) tablets 
de-bossed with 
‘C2’. The cosmetic blue film coating 
is Opadry II containing 
polyvinyl  alcohol,  
titanium  dioxide,  polyethylene  glycol  (PEG)/macrogol, 
talc, Food, Drug, and Cosmetic Act (FD&C) Blue #1 colorant, brilliant blue 
for  coloring  
food  (FCF)  aluminum  
lake,  and  FD&C  blue  
indigo  carmine 
aluminum lake. The 250 mg tablets are white, diamond shaped (15 mm × 
11 mm) tablets de-bossed with ‘C25’.  The 300 mg tablets are yellow, oval 
tablets (16 mm × 8 mm) de-bossed with ‘C3’. 
 
f. 
STORAGE, PREPARATION & STABILITY 
 
1. 
Rucaparib tablets  are  provided  in  high-density  polyethylene  (HDPE) 
bottles (60  tablets  per  bottle) with  child-resistant  caps  and  should  be 
stored 
in the provided containers between 20°C and 25°C, with excursions 
between 15°C  and  30°C permitted. Contact  Clovis  for  temperature 
excursion information. If a storage temperature excursion or other quality 
affecting event is identified, promptly return rucaparib tablets to provided 
containers between 15°C and 30°C and quarantine the supplies. Submit 
a completed Investigational Product Incident Report Form (See Appendix 
18.4)  to Clovis for  determination  of  suitability.  This  form  should  be 
submitted within 24 hours after becoming aware of excursion and prior to 
dosing. 
 
2. 
Repackaging of rucaparib tablets is not acceptable. Please dispense the 
original unopened full bottle(s) of rucaparib.  
 
g. 
NCI-Supplied Agent Ordering and Agent Accountability 
 
NCI-supplied  agents  may  be  requested  by  eligible  participating 
Investigators  (or  their  authorized  designee)  at  each  participating 
institution. The CTEP assigned protocol number (S1900A) must be used 
for  ordering  all  CTEP  supplied  investigational  agents.  The  eligible 
participating  investigators  at  each  participating  institution  must  be 
registered with CTEP, DCTD through an annual submission of FDA Form 


 
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1572 (Statement of Investigator), NCI Biosketch, Agent Shipment Form, 
and  Financial  Disclosure  Form  (FDF).  
If  
there  are  several  participating 
investigators at one institution, CTEP-supplied investigational agents for 
the  study  should  be  ordered  under  the  name  of  one  
lead  participating 
investigator at that institution. 
 
Order  Processing  (OAOP)  application.  Access  to  OAOP  requires  the 
establishment of a CTEP Identity and Access Management (IAM) account 
and the maintenance of an “active” account status, a “current” password, 
and  active  person  registration  status.  For  questions  about  drug  orders, 
transfers, returns, or accountability, call or email PMB any time. Refer to 
the  PMB’s  website  for  specific  policies  and  guidelines  related  
to  agent 
management. 
 
Agent  Inventory  Records – The  investigator,  or  a  responsible  party 
designated  by  the  investigator,  must  maintain  a  careful  record  of  the 
receipt, dispensing and final disposition of all agents received from PMB 
using  the  appropriate  NCI  Investigational  Agent  (Drug)  Accountability 
Record  
(DARF)  available  on  
the  CTEP  
forms  page.  Store  and  maintain 
separate NCI Investigational Agent Accountability Records for each agent, 
strength, formulation and ordering investigator in this protocol. 
 
No  starter  supplies  may  be  ordered.  Participants  must  be  enrolled  and 
registered to protocol S1900A prior to order submission through OAOP.  
 
Useful Links and Contacts 
• CTEP   
Forms,   
Templates,   
Documents:  
http://ctep.cancer.gov/forms/  
• NCI  CTEP  Investigator  Registration  (RCR)  Help  Desk:  
RCRHelpDes@nih.gov  
• PMB policies and guidelines: 
http://ctep.cancer.gov/branches/pmb/agent_management.htm  
• PMB Online Agent Order Processing (OAOP) application:   
https://eapps-ctep.nci.nih.gov/OAOP/pages/login.jspx  
• CTEP Identity and Access Management (IAM) account:   
https://ctepcore.nci.nih.gov/iam/index.jsp  
• CTEP IAM account help:   
ctepreghelp@ctep.nci.nih.gov  
• PMB e-mail:  PMBAfterHours@mail.nih.gov  
 
PMB phone and hours of service:  240/276-6575 Monday through Friday 
between 8:30 am and 4:30 pm (ET) 
 
Supplier:  Rucaparib is an investigational agent supplied to investigators 
by the Division of Cancer Treatment and Diagnosis (DCTD), NCI.  NCI-
supplied agents may be requested by the Principal Investigator (or their 
authorized  designees)  at  each  participating  institution.  Pharmaceutical 
Management  Branch  (PMB)  policy  requires  that  the  agent  be  shipped 
directly to the institution where the patient is to be treated.  PMB does not 
permit  
the  
transfer  of  agents  between  
institutions  
(unless  prior  approval 
from  PMB  
is  obtained).  
  The CTEP  assigned  protocol  number  must  be 
used for ordering all CTEP supplied investigational agents.  
 
1.   
Drug Return and/or Disposition Instruction  
 
a. 
Drug Returns: All unused drug supplies must be returned to the 
PMB. When it is necessary to return study drug (e.g., sealed vials 


 
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remaining  when  expired  vials  are  recalled  by  the  PMB), 
investigators should return the study drug to the PMB using the 
NCI  Return  Agent  Form available  on  the  NCI  home  page 
(http://ctep.cancer.gov). 
 
b. 
Drug  Accountability: The  investigator,  or  a  responsible  party 
designated by the investigator, must maintain a careful record of 
the receipt, disposition, and return of all drugs received from the 
PMB using the Drug Accountability Record Form available on the 
NCI home page (http://ctep.cancer.gov). 
 
 
  
4.0 
STAGING CRITERIA 
 
Patients must have Stage IV or recurrent disease as outlined below (AJCC Cancer Staging Manual, 
8th Edition, 2017): 
 
Stage IVA 
Any T Any N M1a 
   
 
Any T Any N M1b 
 
Stage IVB 
Any T Any N M1c 
 
Primary Tumor (T) 
 
TX 
Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in 
sputum or bronchial washings but not visualized by imaging or bronchoscopy 
T0 
No evidence of primary tumor 
Tis 
Carcinoma in situ 
   
 
Squamous cell carcinoma in situ (SCIS) 
Adenocarcinoma in situ (AIS): adenocarcinoma with pure lepidic pattern, ≤ 3 cm in 
greatest dimension 
T1 
Tumor  ≤  3  cm  in  greatest  dimension,  surrounded  by  lung  or  visceral  pleura,  without 
bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the 
main bronchus) 
T1mi Minimally invasive adenocarcinoma: adenocarcinoma (≤ 3 cm in greatest dimension) with 
a predominantly lepidic pattern and ≤ 5 mm invasion in greatest dimension 
T1a 
Tumor  ≤  1  cm  
in  greatest  dimension.  A  superficial,  spreading  
tumor  of  any  size  whose 
invasive component is limited to the bronchial wall and may extend proximal to the main 
bronchus also is classified as T1a, but these tumors are uncommon.  
T1b 
Tumor ˃ 1 cm but ≤ 2 cm in greatest dimension 
T1c 
Tumor ˃ 2 cm but ≤ 3 cm in greatest dimension 
T2 
Tumor ˃ 3 cm but ≤ 5 cm or having any of the following features: 
• Involves  the  main  bronchus  regardless  of  distance  to  the  carina,  but  without 
involvement of the carina 
• Invades visceral pleura (PL1 or PL2) 
• Associated  with  atelectasis  or  obstructive  pneumonitis  
that  extends  
to  
the  hilar 
region, involving part or all of the lung 
T2 tumors with these features are classified as T2a if ≤ 4 cm or if the size cannot be 
determined and T2b if ˃ 4 cm but ≤ 5 cm. 
T2a   Tumor ˃ 3 cm but ≤ 4 cm in greatest dimension 
T2b 
Tumor ˃4 cm but ≤ 5 cm in greatest dimension 
T3 
Tumor ˃ 5 cm but ≤ 7 cm in greatest dimension or directly invading any of the following:  
parietal pleural (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal 
pericardium, or separate tumor nodule(s) in the same lobe as the primary 
T4 
Tumor  ˃  7  cm  or  
tumor  of  any  size  
invading  one  or  more  of  
the  
following:  
  diaphragm, 
mediastinum,  heart,  great  vessels,  trachea,  recurrent  laryngeal  nerve,  esophagus, 


 
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vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that 
of the primary 
 
Regional Lymph Nodes (N) 
 
NX 
Regional lymph nodes cannot be assessed 
N0 
No regional lymph node metastases 
N1 
Metastasis  in  ipsilateral  peribronchial  and/or  ipsilateral  hilar  lymph  nodes  and 
intrapulmonary nodes, including involvement by direct extension 
N2 
Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s) 
N3 
Metastasis  in  contralateral  mediastinal,  contralateral  hilar,  ipsilateral  or  contralateral 
scalene, or supraclavicular lymph node(s)  
 
Distant Metastasis (M) 
 
M0 
No distant metastasis 
M1 
Distant metastasis 
M1a Separate tumor nodule(s) 
in a contralateral 
lobe; tumor with pleural or malignant pleural or 
pericardial effusion. nodules or malignant pleural (or pericardial) effusion. ** 
M1b Single extrathoracic metastasis in a single organ (including involvement of a single 
nonregional node) 
M1c Multiple extrathoracic metastases in a single organ or in multiple organs 
 
** 
Most  pleural  (and  pericardial)  effusions  with  lung  cancer  are  due  to  tumor.    In  a  few 
patients,  however,  multiple  microscopic  examinations  of  pleural  (pericardial)  fluid  are 
negative for tumor, and the fluid is non-bloody and is not an exudate.  If these elements 
and clinical 
judgment dictate that the effusion 
is not related to the tumor, the effusion should 
be excluded as a staging descriptor. 
 
 
5.0 
ELIGIBILITY CRITERIA 
 
Each  of  
the  criteria  
in  
the  
following  section  must  be  met  
in  order  
for  a  patient  
to  be  considered 
eligible  for  registration.  For  each  criterion  requiring  test  results  and  dates,  please  record  this 
information on the 
Onstudy Form and submit via Medidata Rave® (see Section 14.0).  Any potential 
eligibility issues should be addressed to the Statistics and Data Management Center in Seattle at 
206/652-2267 or LUNGMAPQuestion@crab.org prior to registration. NCI policy does not allow 
for 
waiver 
of 
any 
eligibility 
criterion 
(http://ctep.cancer.gov/protocolDevelopment/policies_deviations.htm).  
 
In  calculating  days  of  tests  and  measurements,  the  day  a  test  or  measurement  is  done  is 
considered Day 0.  Therefore, if a test is done on a Monday, the Monday 4 weeks later would be 
considered Day 28.  This allows for efficient patient scheduling without exceeding the guidelines.  
If Day 7, 14, 16, 28, or 42 falls on a weekend or holiday, the limit may be extended to the next 
working day. 
 
5.1 
Sub-Study Specific Criteria 
 
a. 
Sub-Study Specific Disease Related Criteria/ Laboratory Criteria 
 
1. 
Patients  must  be  assigned  to S1900A. S1900A biomarker  eligibility 
defined as LOH high and/or deleterious BRCA1/2 mutation is as follows 
using the FMI tissue- assay: 
 
Biomarker-
positive group 
Alteration type 
Eligible alteration 


 
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LOH 
Loss of Heterozygosity (LOH) 
Genomic LOH ≥ 21% 
BRCA 
Homologous Recombination 
Deficiency (HRD) 
Deleterious mutations in 
BRCA1 or 
BRCA2 
 
2.   
Patients  must  not  have  had  prior  treatment  with  any  PARP  inhibitor, 
including  rucaparib,  talazoparib,  veliparib,  olaparib,  or  niraparib. For 
information and a 
list of PARP 
inhibitors, please consult the 
S1900A – Poly 
Polymerase  Inhibitors,  Scott  et  al.,  2015  JCO  ref  from  the  link  on  the 
S1900A protocol abstract page of the SWOG (http://swog.org) or CTSU 
(https://www.ctsu.org) websites. 
 
3. 
Patients must be able to take oral medications.  
 
4. 
Patients with known ≥ Grade 3 hypercholesterolemia must be ≤ Grade 2 
(≤400  mg/dL) within  28 days prior  to  sub-study  registration. (Fasting 
cholesterols  is  required  to  be  performed  pre-registration  only  in  those 
patients  where  clinically  indicated.)  Note:  Use  of  medication  to  lower 
cholesterol is acceptable. Caution should be noted for the use of certain 
statin drugs. See Section 3.1c.3. 
 
≥ Grade 3 hypercholesterolemia (“cholesterol high”) is defined by NCI 
CTCAE v5 as blood cholesterol measurement > 400 mg/dL 
 
b. 
Sub-Study Specific Prior/Concurrent Therapy Criteria 
 
1. 
Patients must not be planning to receive any concurrent chemotherapy or 
small  molecular  or  hormonal  
therapy  within  21  days  and biologics (e.g. 
bevacizumab, necitumumab or ramucirumab) or 
immunotherapy within 28 
days prior to sub-study registration and while receiving treatment on this 
study.  Concurrent  use  of  hormones  for  non-cancer-related  conditions 
(e.g.,  insulin  for  diabetes  and  hormone  replacement  therapy)  is 
acceptable. 
 
5.2 
Common Eligibility Criteria for all Sub-Studies 
 
a. 
Disease Related Criteria 
 
1. 
Patients must  not  have EGFR  sensitizing  mutations,  EGFR T790M 
mutation, ALK gene fusion, ROS 1 gene rearrangement, and BRAF V600E 
mutation unless  they  have  progressed  following  all  standard  of  care 
targeted therapy. 
 
2. 
Patients must not have documented evidence of acute hepatitis or have 
an active or uncontrolled infection. 
 
3. 
Patients with a known history of HIV seropositivity: 
 
i. 
Must have undetectable viral load using standard HIV assays in 
clinical practice. 
 
ii. 
Must have CD4 count ≥ 400/mcL. 
 
iii. 
Must not require prophylaxis for any opportunistic infections (i.e., 
fungal, mAC, or PCP prophylaxis). 


 
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iv. 
Must not be newly diagnosed within 12 months prior to sub-study 
registration.  
 
b. 
Prior/Concurrent Therapy Criteria 
 
1. 
Patients must have progressed (in the opinion of the treating physician) 
following the most recent line of therapy. 
 
2. 
Patients  must  not  have  received  any  prior  systemic  therapy  (systemic 
chemotherapy,  immunotherapy  or  investigational  drug)  within  21  days 
prior to sub-study registration. Patients must have recovered (≤ Grade 1) 
from any side effects of prior therapy. Patients must not have received any 
radiation  therapy  within  14  days  prior  to  sub-study  registration.  (See 
Section 5.2c.2 for criteria regarding therapy for CNS metastases). 
 
c. 
Clinical/Laboratory Criteria 
 
1. 
Patients  must  have  measurable  disease  (see S1900A Section  10.1) 
documented by CT or MRI. The CT from a combined PET/CT may be used 
to document only non-measurable disease unless 
it 
is of diagnostic quality 
as  defined  in S1900A Section  10.1c.  Measurable  disease  must  be 
assessed within 28 days prior to sub-study registration. Pleural effusions, 
ascites and 
laboratory parameters are not acceptable as the only evidence 
of  disease.  Non-measurable  disease  must  be  assessed  within  42  days 
prior  to  sub-study  registration.  All  disease  must  be  assessed  and 
documented  on  
the  Baseline  Tumor  Assessment  Form.  Patients  whose 
only measurable disease is within a previous radiation therapy port must 
demonstrate  clearly  progressive  disease  (in  the  opinion  of  the  treating 
investigator)  prior  to  registration.  See S1900A Section 15.0 and 
LUNGMAP Appendix 18.2 for guidelines and submission instructions for 
required central radiology review. CT and MRI scans must be submitted 
for central review via TRIAD. 
 
2. 
Patients  must  have  a  CT  or  MRI  scan  of  
the  brain  
to  evaluate  
for  CNS 
disease  within  42  days  prior  
to  sub-study  
registration.  Patient  must  not 
have  leptomeningeal  disease,  spinal  cord  compression  or  brain 
metastases  unless:  
(1)  metastases  have  been  
locally  
treated  and  have 
remained  clinically  controlled  and  asymptomatic  for  at  least  14  days 
following  treatment,  and  prior  to  registration,  AND  (2)  patient  has  no 
residual  neurological dysfunction and has been  off corticosteroids for at 
least 24 hours prior to sub-study registration. 
 
3. 
Patient  must  not  have  had  a  major  surgery  within  14  days  prior  
to  sub-
study  
registration.  Patient  must  have  
fully  
recovered  
from  
the  effects  of 
prior surgery in the opinion of the treating investigator. 
 
4. 
Patients must have an ANC ≥ 1,500/mcl, platelet count ≥ 100,000 mcl, and 
hemoglobin  ≥  9  g/dL  obtained  within  28  days  prior  to  sub-study 
registration. 
 
5. 
Patients must  have  adequate  hepatic  function  as  defined  by  serum 
bilirubin ≤ Institutional Upper Limit of Normal (IULN) and either ALT or AST 
≤ 2 x IULN within 28 days prior to sub-study registration (if both ALT and 
AST are done, both must be ≤ 2 IULN). For patients with 
liver metastases, 


 
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bilirubin and either ALT or AST must be ≤ 5 x IULN (if both ALT and AST 
are done, both must be ≤ 5 x IULN). 
 
6. 
Patients  must  have  a  serum  creatinine  ≤  the  IULN  OR  or  calculated 
creatinine  clearance  ≥  50  mL/min  using  the  following  Cockroft-Gault 
Formula. This specimen must have been drawn and processed within 28 
days prior to sub-study registration: 
 
Calculated Creatinine Clearance = (140 - age)  X (actual body weight in 
kg†)  
72 x serum creatinine* 
 
Multiply this number by 0.85 if the patient is a female.  
 
† The kilogram weight is the patient weight with an upper limit of 140% of 
the IBW. 
* Actual lab serum creatinine value with a minimum of 0.7 mg/ dL. 
 
7. 
Patients must have Zubrod performance status 0-1 (see S1900A Section 
10.4) documented within 28 days prior to sub-study registration. 
 
8. 
Patients must not have any Grade III/IV cardiac disease as defined by the 
New  York  Heart  Association  Criteria  
(i.e.,  patients  with  cardiac  disease 
resulting in marked limitation of physical activity or resulting in inability to 
carry  on  any physical  activity  without  discomfort),  unstable  angina 
pectoris,  and  myocardial  infarction  within  6  months,  or  serious 
uncontrolled cardiac arrhythmia (see S1900A Appendix 18.1). 
 
9. 
Pre-study history and physical exam must be obtained within 28 days prior 
to sub-study registration. 
 
10. 
No other prior malignancy is allowed except for the following: adequately 
treated  basal cell  or  squamous  cell  skin  cancer,  
in  situ  cervical  cancer, 
adequately treated Stage I or II cancer from which the patient is currently 
in  complete  remission,  or  any  other  cancer  
from  which  
the  patient  has 
been disease free for five years. 
 
11. 
Patients must not be pregnant or nursing. Women of reproductive potential 
must  have  agreed  
to  use  an  effective  contraceptive  method  during  
the 
study  and 6 months  after completion  of study  treatment. Men  of 
reproductive potential must have agreed to use an effective contraceptive 
method during the study and 3 months after completion of study treatment. 
A  woman  
is  considered  
to  be  of  
"reproductive  potential"  
if  she  has  had 
menses at any time in the preceding 12 consecutive months. In addition 
to routine contraceptive methods, "effective contraception" also includes 
heterosexual celibacy and surgery intended to prevent pregnancy (or with 
a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral 
oophorectomy  or  bilateral  tubal  ligation.  However,  if  at  any  point  a 
previously  celibate  patient  chooses  to  become  heterosexually  active 
during the time period for use of contraceptive measures outlined in the 
protocol,  he/she  is  responsible  for  beginning  contraceptive  measures 
during the study and for 6 months after study completion for females and 
3 months after study completion for males. 
 
5.3 
Specimen Submission Criteria 
 


 
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a. 
Patients must agree to have blood specimens submitted for circulating tumor DNA 
(ctDNA) as outlined in Section 15.0. 
 
b. 
Patients must also be offered participation 
in banking and 
in the correlative studies 
for collection and future use of specimens as described in S1900A Section 15.0.  
 
5.4 
Regulatory Criteria 
 
a. 
Patients must be 
informed of the 
investigational nature of this study and must sign 
and  give  written  informed  consent  in  accordance  with  institutional  and  federal 
guidelines. 
 
b. 
As a part of the OPEN registration process (see S1900A Section 13.0 for OPEN 
access instructions) the treating institution
's identity is provided in order to ensure 
that the current (within 365 days) date of 
institutional review board approval for this 
study has been entered in the system. 
 
c. 
Patients  with  impaired  decision-making  capacity  are  eligible  as  long  as  their 
neurological or psychological condition does not preclude their safe participation 
in the study (e.g., tracking pill consumption and reporting adverse events to the 
investigator). 
 
 
6.0 
STRATIFICATION FACTORS 
 
Patients will be stratified into two cohorts based on their histology. 
 
Cohort 1: Patients with squamous cell lung cancer. 
 
Cohort 2: Patients with non-squamous cell lung cancer (adenocarcinoma, large cell, NSCLC NOS, 
mixed histology with any non-squamous component). 
 
 
7.0 
TREATMENT PLAN 
 
For treatment or dose modification questions, please contact Dr. Jonathan W. Riess and Dr. Paul 
Wheatley-Price  at S1900AMedicalQuery@swog.org.  
 For  dosing  principles  or  questions,  please 
consult  the  SWOG  Policy  #38  "Dosing  Principles  for  Patients  on  Clinical  Trials"  at 
https://www.swog.org/sites/default/files/docs/2017-11/Policy38.pdf. 
 
7.1 
Disease Assessment 
 
See Section 9.0 for disease assessment time points. Submit scans as outlined in Section 
14.0 and Section 15.0. 
 
Disease Assessment During Treatment 
CT or MRI (the same method used at pre-study to meet the eligibility criteria 
in Section 5.2) 
must be repeated every 6 weeks (± 7 day window), for the first year regardless of treatment 
delays,  then  every 12  weeks (±  7  day  window) until  disease  progression and 
discontinuation of protocol treatment. The 6 weeks should start from Cycle 1 Day 1. 
 
Pre-study Brain CT/MRI 
is required 42 days prior to sub-study registration per Section 5.2. 
If patient has brain metastases at baseline, scans must use the same modality as baseline 
and be repeated every 12 weeks (± 7 day window) regardless of treatment delays, while 
on treatment. 
 


 
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Disease Assessment During Off Protocol Treatment, Prior to Progression 
After off protocol treatment prior to progression, disease assessments 
must continue every 
12 weeks (± 7 day window) until progression. 
 
If patient has brain metastases at baseline, continue brain CT or MRI scans (same modality 
as  baseline)  after  off  protocol  
treatment  prior  
to  progression,  as  clinically  
indicated. For 
alignment with the protocol and good clinical practice, recommended frequency of brain 
scans  after  off  protocol  
treatment  
(and  prior  
to  progression)  
is  at  
least  every  12  weeks, 
unless more frequent scans are clinically appropriate. 
 
7.2 
Precautions 
 
Photosensitivity 
Patients should use common precautions when going outside, such as applying sunscreen 
and/or  covering  exposed  skin  with  clothing  and  wearing  a  hat  and  sunglasses,  as 
photosensitivity has been observed. 
 
Concomitant Medications 
Use  caution  for  concomitant  medications  that  are  substrates  of  CYP1A2,  CYP2C9, 
CYP2C19 and/or CYP3A, and adjust dosage 
if clinically 
indicated. If co-administration with 
warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing the frequency of 
international  normalized  ratio  (INR)  monitoring. Although  
in  vitro  rucaparib  metabolism 
mediated  by  CYP3A4  was  slow,  a  significant  contribution  of  CYP3A4  
in  vivo  cannot  be 
excluded.  Caution  should  be  used  
for  concomitant  use  of  strong  CYP3A4  
inhibitors  or 
inducers. Selection of an alternative concomitant medication is recommended. 
 
Because rucaparib is a strong BCRP inhibitor, concomitant use of drugs that are BCRP 
substrates (e.g.,  rosuvastatin)  are not  allowed during  the  treatment  study. See  the 
following url for examples:  
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugI
nteractionsLabeling/ucm093664.htm#table5-2   
 
See Section 3.0 and Appendix 18.5 for additional details. 
 
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) 
MDS/AML  occurred  
in  patients  exposed  
to rucaparib,  
including  one  
fatal  event  of  AML. 
Monitor patients for hematological toxicity at baseline and monthly thereafter. Discontinue 
if MDS/AML is confirmed.  
 
If AML/MDS is suspected, then patient should be referred to a hematologist and analysis 
of  the  bone  marrow with  cytogenetic  studies  are  recommended  according  to  standard 
hematologic practice. Bone marrow analysis should include a bone marrow aspirate per 
standard hematologic practice. 
 
Please  see Section  8.3 for  additional  guidance  on  neutropenia,  thrombocytopenia  and 
anemia toxicities. 
 
Embryo-Fetal Toxicity 
Rucaparib can cause fetal harm. Advise females of reproductive potential of the potential 
risk to a fetus and to use effective contraception.  
 
7.3 
Pre-Medication 
 
a. 
Pre-medication associated with standard drug administration and supportive care 
(including anti-diarrheals, antibiotics, diuretics or other medications) may be given 
as  indicated  by  the  current  American  Society  of  Clinical  Oncology  (ASCO) 
guidelines. 


 
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7.4 
Treatment – S1900A 
 
Agent 
Dose 
Route 
Day 
    Schedule 
   
 
 
Rucaparib 
600 mg** 
Oral                BID            Continuous 
 
 
 
   
      
   
 
*   Note:  One cycle = 21 calendar days 
** Total daily dose = 1200mg 
 
Site and patient instructions can be found in the Intake Calendar (Section 18.6). 
 
7.5 
Drug Compliance Documentation 
 
Drug  compliance  
for  
rucaparib  will  be  
recorded  by  patients  
in  
the  
Intake  Calendar (see 
www.ctsu.org). Institutional CRAs will review and ascertain patient adherence with protocol 
therapy at the end of treatment for each cycle.  Calendar should be kept in the patient
's 
clinic chart. Sites utilizing the CIRB must use the Intake Calendar provided.   
 
7.6 
Criteria for Removal from Protocol Treatment 
 
a. 
Progression of disease or symptomatic deterioration (as defined in Sections 10.2d 
and 10.2e). * 
 
*  Upon  progression,  
the  Request  
for  New  Sub-Study  Assignment  Form  may  be 
submitted under the patient’s screening protocol (LUNGMAP or S1400) to receive 
a new sub-study assignment (see Section 14.4i). 
 
b.   
Unacceptable toxicity.  
 
c. 
Treatment delay for any reason > 28 days (or as noted in Section 8.0). 
 
d. 
The patients may withdraw from the protocol treatment at any time for any reason. 
 
7.7 
Discontinuation of Treatment 
 
All  reasons  
for  discontinuation  of  
treatment  must  be  documented  
in the  Off Treatment 
Notice. 
 
7.8 
Follow-Up Period 
 
All patients will be followed until death or 3 years after sub-study registration, whichever 
occurs first. 
 
Note: Patients who enroll on a new sub-study following progression must continue follow-
up on this sub-study, in addition to follow-up on the new sub-study. 
 
 
8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS 
 
8.1 
NCI Common Terminology Criteria for Adverse Events 
 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for toxicity and Serious Adverse Event reporting.  A copy of the CTCAE Version 
5.0 can be downloaded from the CTEP home page (http://ctep.cancer.gov).  All appropriate 
treatment areas should have access to a copy of the CTCAE Version 5.0. 
 


 
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8.2 
General Considerations 
 
a. 
Missed doses are to be omitted rather than made up. 
 
b. 
If multiple toxicities  are  experienced,  dose  modifications  will  be  based  on  the 
toxicity requiring the largest dose reduction. 
 
c. 
Once  dose  is  reduced,  patients  will  continue  at  the  new  dose.  No  dose  re-
escalations are allowed. 
 
d. 
A maximum of three dose reductions are allowed. 
 
e. 
The maximum dose delay for any reason is 28 days. 
 
See Section 7.3 for patient instructions. 
 
8.3 
Dose Modifications – Rucaparib 
 
Dose modifications should be made based on the observed toxicity, as summarized in the 
tables below.  
 
DRUG 
DOSE LEVEL 
DOSE 
Rucaparib 
Full 
600 mg BID   
 
-1 Level 
500 mg BID   
 
-2 Level 
400 mg BID   
 
-3 Level 
300 mg BID   
 
-4 Level 
Discontinue 
 
As  discussed  above,  the  most  common side effects  of  rucaparib  treatment  include 
gastrointestinal disorders (nausea, vomiting, diarrhea, and constipation), asthenia/fatigue, 
clinical  chemistry  elevations  (ALT/AST,  creatinine,  and cholesterol),  myelosuppression 
(decreases  in  hemoglobin,  lymphocytes,  platelets,  and  neutrophils),  dysgeusia,  and 
decreased appetite.  Modification of rucaparib dose may be a necessary component of AE 
management,  and  study  specific  protocol  guidelines  for  dose  modifications  should  be 
followed.  Dose  interruptions,  with  or  without  subsequent  dose  reductions,  may  help  to 
ameliorate AEs attributed to rucaparib therapy. 
 
Treatment with rucaparib should be held if any of the following are observed and a dose 
reduction should be considered or implemented.  
 
• Grade 3 or 4 hematologic toxicity (except for lymphocyte count decrease). 
 
• Grade 3 or 4 non-hematologic toxicity (except for alopecia, nausea, vomiting, or 
diarrhea  adequately controlled with systemic antiemetic/antidiarrheal  medication 
administered in standard doses according to the study center routines). Grade 3 
or Grade 4 ALT/AST elevations should be managed as described below (Table 2).  
 
• In addition, and at the discretion of the investigator, the dose of rucaparib may be 
held and/or reduced for Grade 2 toxicity not adequately controlled by concomitant 
medications and/or supportive care. 
 
 


 
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Table 1: Bone Marrow Suppression Dose Modifications/Interruptions 
Toxicity  
Dose Modification/Interruption 
Toxicity Management 
Anemia 
≥ Grade 3 
Hold   protocol   therapy   until 
resolution to ≤ Grade 2. May resume 
protocol therapy at next lower dose. 
 
If   dose   interruption   is >28 
consecutive   days,   permanently 
discontinue protocol therapy.  
 
 
If  persists >14  consecutive  days, 
or  a  dependence  upon blood 
transfusion occurs, then complete 
weekly   blood   counts   until 
resolution.* 
 
 
Neutropenia 
≥ Grade 3 
Hold  rucaparib  until  resolution  
to  ≤ 
Grade 2 and resume at lower dose. 
For   patients   with   persistent 
neutropenia that does not stabilize 
or recover with dose modification, 
consider   additional   diagnostic 
evaluation, 
including bone marrow 
examination.* 
Thrombocytopenia 
≥ Grade 3 
Evaluate  
for  other  medications  
that 
may induce  thrombocytopenia  and 
discontinue/modify   
these 
medications  if  indicated  in  the 
opinion  of  the  investigator.  Hold 
rucaparib until resolution to ≤ Grade 
1 and resume at lower dose. 
For   patients   with   persistent 
thrombocytopenia  that  does  not 
stabilize  or  recover  with  dose 
modification,  consider  additional 
diagnostic  evaluation,  including 
bone marrow examination.* 
* If  a  Grade ≥ 3  anemia,  neutropenia,  or  thrombocytopenia  occurs  and  after  28  days  of 
interruption of rucaparib, these cytopenias have not 
improved to CTCAE Grade ≤ 2, then patient 
should be referred to a hematologist and analysis of the bone marrow with cytogenetic studies 
are recommended according to standard hematologic practice. Bone marrow analysis should 
include a bone marrow aspirate per standard hematologic practice. 
 
 


 
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Table 2: ALT/AST Elevations Dose Modifications/Interruptions 
Toxicity  
Dose Modification/Interruption 
Toxicity Management 
Grade 3 
Hold protocol therapy until resolution 
to  ≤  Grade  2.  Monitor  
liver  
function 
tests. If resolves to ≤ Grade 2 within 
2  weeks,  continue  protocol  
therapy 
at same dose.  
 
If  persists  beyond  2  weeks  or 
bilirubin  or  alkaline  phosphatase  
is 
elevated, hold protocol therapy until 
≤  Grade  2  and  resume  at  dose 
reduction.  
 
If  elevation  returns  on  a  second 
occasion, reduce dose.  
 
See Section  2.3 (Overview  of 
Safety)  for  
information  on  transient 
elevation that can occur 
in the first 2-
3 weeks. 
In  the  absence  of  other  signs  of 
liver dysfunction: 
 
• 
Monitor liver function tests weekly 
until resolution to ≤ Grade 2. 
• 
Continuation  of  protocol therapy 
with  elevation  of  ALT/AST  up  to 
Grade  3  is  allowed  provided 
bilirubin  is  <  ULN  and  alkaline 
phosphatase is < 3 x ULN. 
Grade 4 
Hold  protocol  therapy  until  values 
have returned to ≤ Grade 2 or better, 
then  
resume  
rucaparib  with  a  dose 
reduction.  
Monitor  
liver  
function  
tests  weekly 
for  3  weeks  after  rucaparib  has 
been restarted. 
 
Table 3: Cholesterol Elevations Dose Modifications/Interruptions 
Toxicity  
Dose Modification/Interruption 
Toxicity Management 
Grade 3 
Hold  protocol  therapy  until values 
return  to  ≤  Grade  2(≤400  mg/dL) 
fasting  cholesterol. Then  resume 
rucaparib at same dose. 
Consider the use of concomitant 
treatment with a HMG-CoA 
reductase inhibitor (commonly 
known as statin). However, caution 
should be noted for the use of 
certain statin drugs. See Section 
3.1c.3. 
 
 
8.4 
Dose Modification Contacts 
 
For treatment or dose modification questions, please contact Dr. Jonathan Riess and Dr. 
Paul  Wheatley-Price at S1900AMedicalQuery@swog.org. For  dosing  principles  or 
questions, please consult the SWOG Policy #38 "Dosing Principles for Patients on Clinical 
Trials" at https://www.swog.org/sites/default/files/docs/2017-11/Policy38.pdf. 
 
8.5 
Adverse Event Reporting 
 
Toxicities  (including  suspected  reactions)  that  meet  the  expedited  reporting  criteria  as 
outlined 
in Section 16.0 of S1900A must be reported to the Operations Office, Study Chair 
and NCI via CTEP-AERS, and to the IRB per local IRB requirements.  
 
 


 
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9.0 
STUDY CALENDAR 
 
9.1 
Rucaparib 
 
 
  
PRE-STUDY 
(w/in 28 days 
prior to 
registration, 
unless 
otherwise 
noted) 
Cycle Length = 21 days 
(+/- 3 days) 
At Off 
Tx 
Off Tx FU Prior to 
Prog  
Off Tx FU After 
Prog 6  
 
REQUIRED 
STUDIES 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 Subsequent 
Cycles 4 
 
 
PHYSICAL 
  
 
History & Physical 
Exam 
X 
X 
X 
X 
X 
X 
X 
X 5 
  
 
Weight & 
Performance 
Status 
X 
X 
X 
X 
X 
X 
X 
X 5 
  
 
Intake Calendar 
9 
  
X 
X 
X 
X 
X 
  
  
  
 
Toxicity Notation 
  
X 
X 
X 
X 
X 
X 
X 8 
X 8 
 
Smoking Status 
Assessment 
X 
  
  
  
  
  
X 
  
  
  
LABORATORY 
  
  
  
  
  
  
  
If labs obtained w/in 14 days 
prior to tx, tests need not be 
repeated on C1D1. 
Up to 48 hours prior to Day 1 tx 
  
  
  
CBC/Diff/Platelets/ 
Hgb 
X 
X  
X 
X 
X 
X 
X 
X 8 
X 8 
 
Serum Bilirubin 
X 
X  
X 
X 
X 
X 
X 
X 8 
X 8 
 
ALT or AST 3 
X 
X  
X 
X 
X 
X 
X 
X 8 
X 8 
 
Alkaline 
Phosphatase 
X 
X  
X 
X 
X 
X 
X 
X 8 
X 8 
 
Cholesterol 
(fasting)
12 
X 
(per Sec. 
5.1a4) 
X  
X 
X 
X 
X 
X 
X 8 
X 8 


 
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PRE-STUDY 
(w/in 28 days 
prior to 
registration, 
unless 
otherwise 
noted) 
Cycle Length = 21 days 
(+/- 3 days) 
At Off 
Tx 
Off Tx FU Prior to 
Prog  
Off Tx FU After 
Prog 6  
 
REQUIRED 
STUDIES 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 Subsequent 
Cycles 4 
 
 
Serum 
Creatinine/Calc 
CrCl 
X 
X  
X 
X 
X 
X 
X 
X 8 
X 8 
 
Serum Pregnancy 
Test 
 
X 11 
(w/in 7 
days prior 
to C1D1) 
 
 
 
 
 
 
 
 
X-RAYS & SCANS 
 
CT or MRI for 
Disease 
Assessment 1 
X  
  
  
X  
(every 6 
wks, ± 7 
days) 
  
X  
(every 6 
wks, ± 7 
days) 
  
X 5 
 (every 12 wks, ± 7 
days) 
  
 
Brain CT/MRI 
2 
X  
  
  
  
X  
(every 12 
wks, ± 7 
days)  
X  
(every 12 
wks, ± 7 
days) 
  
X  
(every 12 wks, ± 7 
days) 
  
 
SPECIMEN SUBMISSION 
 
ctDNA Whole 
Blood 
 
X 10  
  
  
  
  
  
  
  
 
Buffy Coat /Plasma 
for Banking13 
X 
(pre-tx)  
X  
X  
X  
  
  
  
X 
(first progression) 
 
TREATMENT           
  
 
(21 day cycle) 
 
Rucaparib9 
  
X 
X 
X 
X 
X 
  
  
  
 
NOTE: Forms are found on the protocol abstract page on the CTSU website (www.ctsu.org).  Forms submission guidelines are found in Section 14.0. 
NOTE: Unless 
indicated otherwise 
in the protocol, scheduled procedures and assessments (treatment administration, toxicity assessment for continuous 
treatment,  disease  assessment,  specimen  collection  and  
follow-up  activities)  must  
follow  
the  established  SWOG  guidelines  on  
the  allowed 
protocol  visits/treatment  window  as  outlined  in https://www.swog.org/sites/default/files/docs/2019-07/BestPracticesupdate.pdf.  SWOG  Best 
Practices allows for a ± 3 day window for 21-day cycles. 


 
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Footnotes for Calendar 9.1 (Rucaparib): 
 
 
 
 
 
 
 
 
 
 
 
1 CT or MRI (the same method used at pre-study to meet the eligibility criteria in Section 5.2 S1900A) must be repeated every 6 weeks (± 7 day 
window) for the first year, regardless of treatment delays, then every 12 weeks (± 7 day window) until disease progression and discontinuation 
of protocol treatment. The 6 weeks should start from Cycle 1 Day 1. Submit scans as outlined in Section 14.0 and Section 15.0 S1900A.   
2 Brain CT or MRI is required per Section 5.2.  If patient has brain metastases at baseline, brain scans must use the same modality as baseline 
and be repeated every 12 weeks (± 7 days) regardless of treatment delays, while on treatment. If patient has brain metastases at baseline, 
continue brain CT or MRI scans (same modality as baseline) after off protocol treatment prior to progression, as clinically 
indicated. For alignment 
with the protocol and good clinical practice, recommended frequency of brain scans after off protocol treatment (and prior to progression) is at 
least every 12 weeks, unless more frequent scans are clinically appropriate. 
3 If ALT/AST elevation of ≥ Grade 3, monitor liver function tests weekly until resolution to ≤ Grade 2. See Section 8.3 Table 2. 
4 During continued treatment, 
items marked under physical and laboratory should be performed prior to every subsequent cycle, unless otherwise 
noted.  Disease assessments and image submission are to take place every 6 weeks (± 7 days) regardless of treatment delays. Treatment and 
evaluation will continue until any one of the criteria in Section 7.5 S1900A is met. 
5 After off protocol treatment prior to progression, patients should be followed by repeating indicated studies every 12 weeks or more often as 
clinically indicated until progression. Disease assessments should continue every 12 weeks until progression. 
6 After off protocol treatment after progression, follow-up will occur (with lab tests and scans performed at the discretion of the treating physician) 
every 6 months for 2 years then at end of 3 years from date of sub-study registration. Note: Patients who enroll on a new sub-study following 
progression must continue follow-up on this sub-study, in addition to follow-up on the new sub-study. 
7 This footnote has been removed. 
8 Assessments should continue until resolution of all acute adverse events. 
9 The CRA will review the Intake Calendar  at the end of each cycle and confirm patient  adherence (See Intake Calendar for site and patient 
instructions in Section 18.6) 
10 ctDNA must be collected prior to treatment initiation per Section 15.3.  Note: Kits must be ordered and will take up to 3 days to arrive. 
11 Women of child bearing potential must have a negative serum pregnancy test within 7 days prior to Cycle 1 Day 1. 
12 Pre-Study  fasting  cholesterol  to  be  performed  as  clinically  indicated  per  Section  5.1a4. It  is  acceptable  to  perform  a  non-fasting  test  for 
subsequent timepoints; however, if the participant experiences a ≥ Grade 3 hypercholesterolemia, a follow-up fasting cholesterol check must be 
performed.  If ≥ Grade 3 hypercholesterolemia is confirmed, proceed to managing the toxicity as outlined in Section 8.3 Table 3.  
13 See Section 15.2 for details. 


 
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10.0 CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS 
 
10.1 Measurability of Lesions (28) 
 
a. 
Measurable disease: Measurable disease is defined differently for lymph nodes 
compared with other disease and will be addressed in a separate section below. 
 
1. 
Lesions that  can  be  accurately  measured  in  at  least  one  dimension 
(longest diameter to be recorded) as ≥ 2.0 cm by chest x-ray, by ≥ 1.0 cm 
with CT or MRI scans, or ≥ 1.0 cm with calipers by clinical exam. All tumor 
measurements must be recorded in decimal fractions of centimeters (or 
millimeters). 
 
The  defined  measurability  of  lesions  on  CT  scan  is  based  on  the 
assumption  that  CT  slice  thickness  is  0.5  cm  or  less. It  is strongly 
recommended that CT slice of 0.5 cm be used.  If CT scans have slice 
thickness greater than 0.5 cm, the minimum size for a measurable lesion 
should be twice the slice thickness.   
 
2. 
Malignant lymph nodes are to be considered pathologically enlarged and 
measurable  
if it  measures  ≥ 1.5 cm in SHORT AXIS (greatest diameter 
perpendicular to the long axis of the lymph node) when assessed by scan 
(CT scan slice recommended being no greater than 0.5 cm). 
 
b. 
Non-measurable disease:  All other lesions (or sites of disease), including small 
lesions (longest diameter < 1.0 cm or pathologic lymph nodes with ≥ 1.0 cm to < 
1.5  cm  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  as  are  previously 
radiated lesions that have not progressed. 
 
c. 
Notes on measurability 
 
1. 
For CT and MRIs, the same type of scanner should be used and the 
image 
acquisition  protocol  should  be  followed  as  closely  as  possible  to  prior 
scans.  It  is  no  longer  necessary  to  distinguish  between  spiral  and 
conventional CT. 
 
2. 
Body scans should be performed with breath-hold scanning techniques, if 
possible.  
 
3. 
PET-CT: At present, the low dose or attenuation correction CT portion of 
a  PET-CT  is  not  always  of  optimal  diagnostic  CT  quality  for  use  with 
RECIST  measurements. However,  
if  
the site can document that the CT 
performed  as  part  of  a  PET-CT  is  of  identical  diagnostic  quality  to  a 
diagnostic CT, then the CT portion of the PET-CT can be used for RECIST 
measurements  and  can  be  used  
interchangeably  with  stand-alone  CT. 
The slice thickness of 0.5 cm or less is highly recommended. If CT scans 
have slice thickness > 0.5 cm, the minimum size for a measurable lesion 
should be twice the slice thickness. 
 
4. 
Ultrasound:  Ultrasound  is  not  useful  in  assessment  of  lesion  size  and 
should not be used as a method of measurement. 
 
5. 
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. 


 
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6. 
If a target lesion becomes very small some radiologists indicate that it is 
too  small  to  measure.  If  the  lesion  is  actually  still  present,  a  default 
measurement of 0.5 cm should be applied. If the radiologist believes the 
lesion has gone, a default measurement of 0.0 cm should be recorded. 
 
10.2 Objective Status at Each Disease Evaluation 
 
Objective  Status  
is  to  be  recorded  at  each  evaluation.  All  measurable  
lesions  up  to  a 
maximum of 2 lesions per organ, 5 lesions in total, representative of all involved organs, 
should  be  
identified  as target lesions  at  baseline.  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.  Measurements  must  be  provided  for  target  measurable  
lesions, 
while presence or absence must be noted for non-target measurable and non-measurable 
disease.  
 
For studies that use disease progression as an endpoint, all potential sites of metastases 
should be evaluated at each time point rather than following only sites of disease identified 
at baseline. It is acceptable to image only the areas of the body most likely to be involved 
with metastatic disease for the tumor type (chest, abdomen, pelvis, and/or bone scan are 
typical),  with  
the  addition  of  any  areas  with  suspected  
involvement  based  upon  clinical 
symptoms.  For study-specific imaging requirements, see the Study Calendar in Section 
9.0. 
 
a. 
Complete Response (CR): Complete disappearance of all target and non-target 
lesions (with the exception of lymph nodes mentioned below). No new lesions. No 
disease related symptoms.  Any lymph nodes (whether target or non-target) must 
have reduction in short axis to < 1.0 cm. All disease must be assessed using the 
same technique as baseline. 
 
b. 
Partial  Response  (PR): Applies  only  
to  patients  with  at  
least  one  measurable 
lesion.  Greater  than  or  equal  to  30%  decrease  under  baseline  of  the  sum  of 
appropriate  diameters  of  all  target  measurable  lesions.  No  unequivocal 
progression  of  non-measurable  disease.  No  new  
lesions.  All  
target  measurable 
lesions must be assessed using the same techniques as baseline. 
 
c. 
Stable: Does not qualify for CR, PR, Progression or Symptomatic Deterioration. 
All  
target  measurable  
lesions  must  be  assessed  using  
the  same  
techniques  as 
baseline. 
 
d. 
Progression: One or more of the following must occur: 20% increase in the sum 
of appropriate diameters of target measurable 
lesions over smallest sum observed 
(over  baseline  if  no  decrease  during  therapy)  using  the  same  techniques  as 
baseline,  as  well  as  an  absolute  increase  of  at  least  0.5  cm.  Unequivocal 
progression of non-measurable disease 
in the opinion of the treating physician (an 
explanation must be provided).  Appearance of any new lesion/site. Death due to 
disease  without  prior  documentation  of  progression  and  without  symptomatic 
deterioration (see 10.2e). 
 
 
 


 
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Notes on progression and new lesions:  
 
1. 
For equivocal findings of progression (e.g. very small and uncertain new 
lesions;  cystic  changes  or  necrosis  
in  existing  lesions),  treatment  may 
continue  until the next scheduled  assessment.  If at the next scheduled 
assessment, progression is confirmed, the date of progression should be 
the earlier date when progression was suspected. 
 
2. 
FDG-PET  imaging  can  complement  regular  scans  in  identifying  new 
lesions according to the following algorithm.   
• Negative  FDG-PET  at  baseline,  with  a  positive  FDG-PET  at 
follow-up is a sign of progression based on a new lesion. 
o No  FDG-PET  at  baseline  and  a  positive  FDG-PET  at  
follow-up 
corresponding  to  a  potential  new site  of  disease  must  have  a 
confirmation by anatomical assessment (e.g. CT, MRI, x-ray) as 
new site of disease to be considered progressive disease. In such 
a case, the date of progressive disease will be the date of the 
initial 
abnormal FDG-PET.   
 
3. 
A previous  abnormal  target  lymph  node  that  became  normal  and 
subsequently  enlarged  
in  size  meeting  
the  criteria  
for  a  pathologic  and 
measurable lymph node (a short axis of ≥ 1.5 cm) should be added to the 
sum of diameters to determine if criteria for progression are met based on 
target lesions. 
 
4. 
A  previously  abnormal  non-target  
lymph  node  
that  became  normal  and 
subsequently  recurred  must  meet  
the  criteria  
for  progression  based  on 
non-target lesions to be considered progression. 
 
5. 
A normal lymph node at baseline (<1.0 cm) that subsequently becomes 
pathologic  is  considered  a  new  lesion  and  should  be  considered 
progression. 
 
6. 
If  a  single  pathologic  lymph  node  is  driving  the  progression  event, 
continuation  of  treatment/follow-up  and  confirmation  by  a  subsequent 
exam should be contemplated. If 
it becomes clear that the new 
lymph node 
has not resolved, or has increased in size, the date of progression would 
be the date the new lymph node was first documented. 
 
e. 
Symptomatic  deterioration:  Global  deterioration  of  health  status  requiring 
discontinuation  of  treatment  without  objective  evidence  of  progression.  Efforts 
should be made to obtain objective evidence of progression after discontinuation. 
 
f. 
Assessment  inadequate,  objective  status  unknown: Progression  or 
symptomatic  deterioration  has  not  been  documented,  and  one  or  more  target 
measurable 
lesions have not been assessed or 
inconsistent assessment methods 
were used. 
Objective status notes: 
1. 
Non-measurable  and  non-target  measurable  disease  do  not  affect 
Objective Status in determination of CR (must be absent--a patient who 
otherwise  has  a  CR,  but  who  has  non-measurable  or  non-target 
measurable disease present or not assessed, will be classified as having 
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determination  of  progression  (if  new  sites  of  disease  develop  or  if 
unequivocal progression occurs in the opinion of the treating physician).  
2. 
An objective status of PR or stable cannot follow one of CR. Stable can 
follow PR only in the rare case that tumor increases too little to qualify as 
progression, but enough that a previously documented 30% decrease no 
longer holds. 
3. 
In  cases  for  which  initial  flare  reaction  is  possible (hypercalcemia, 
increased  bone  pain,  erythema  of  skin  
lesions),  objective  status  
is  not 
progression  unless either symptoms persist beyond 4 weeks or there  
is 
additional evidence of progression. 
4. 
Lesions that appear to increase in size due to presence of necrotic tissue 
will not be considered to have progressed.  
5. 
For bone disease documented on bone scan only, increased uptake does 
not  constitute  unequivocal  progression.  However,  increase  in  the  soft 
tissue component of a lesion as measured by CT or MRI would constitute 
progression. 
6. 
Appearance  of  new  pleural  effusions  does  not  constitute  unequivocal 
progression unless cytologically proven of neoplastic  origin, since some 
effusions  are  a  toxicity  related  to  therapy  or  other  medical  conditions. 
Increase 
in the size of an existing effusion does not constitute unequivocal 
progression, since the fluid status of the patient could alter the size of the 
effusion.  
7. 
If CR determination depends on a lesion for which the status is unclear by 
the required tests, it is recommended the residual lesion be investigated 
with biopsy or fine needle aspirate.  
8. 
Lymph nodes are considered one organ.  Only two lymph nodes should 
be  selected  as  target  
lesions.    Other  
involved  
lymph  nodes  should  be 
assessed and followed as non-target lesions. 
9. 
“Paired” organs, 
i.e. 
lungs, kidneys and ovaries, are considered one organ.   
10. 
Pleural-based lung lesions are considered part of the lung in determining 
target  lesions  (a  maximum  of  two  lung  lesions  should  be  selected), 
whereas pleural effusions/thickening can be reported as a separate site. 
 
10.3 Best Response 
 
This is calculated from the sequence of objective statuses. 
 
a. 
CR:    Two  or  more  objective  statuses  of  CR  a  minimum  of  four  weeks  apart 
documented before progression or symptomatic deterioration. 
 
b. 
PR:  Two or more objective statuses of PR or better a minimum of four weeks apart 
documented before progression or symptomatic deterioration, but not qualifying as 
CR. 
 
c. 
Unconfirmed CR:  One objective status of CR documented before progression or 
symptomatic deterioration but not qualifying as CR or PR. 
 
d. 
Unconfirmed PR:  One objective status of PR documented before progression or 
symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR. 
 
e. 
Stable/no  response:    At  least  one  objective  status  of  stable/no  response 
documented  at  least  6  weeks  after  registration  and  before  progression  or 
symptomatic deterioration, but not qualifying as anything else above. 
 
f. 
Increasing  disease:    Objective  status  of  progression  within  12  weeks  of 
registration, not qualifying as anything else above. 
 


 
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g. 
Symptomatic deterioration: Objective status of symptomatic deterioration within 12 
weeks of registration, not qualifying as anything else above.   
 
h. 
Inadequate  assessment,  response  unknown:    Progression  or  symptomatic 
deterioration  greater  than  12  weeks  after  registration  and  no  other  response 
category applies. 
 
10.4 Performance Status 
 
Patients will be graded according to the Zubrod Performance Status Scale. 
 
POINT 
DESCRIPTION 
 
0 
Fully active, able to carry on all pre-disease performance without 
restriction. 
 
1 
Restricted 
in physically strenuous activity but ambulatory and able 
to  carry  out  work  of  a  light  or  sedentary  nature,  e.g.,  light 
housework, office work. 
 
2 
Ambulatory and capable of self-care but unable to carry out any 
work activities; up and about more than 50% of waking hours. 
 
3 
Capable of limited self-care, confined to bed or chair more than 
50% of waking hours. 
 
4 
Completely  disabled;  cannot  carry  on  any  self-care;  totally 
confined to bed or chair. 
 
10.5 
Time to Death 
 
From date of sub-study registration  to date of death due to any cause.  Patients 
last known 
to be alive are censored at date of last contact. 
 
10.6 Investigator-Assessed Progression-Free Survival 
 
From date of sub-study registration to date of first documentation of progression assessed 
by 
local review or symptomatic deterioration (as defined above), or death due to any cause.  
Patients last known to be alive without report of progression are censored at date of last 
disease  assessment.  For  patients  with  a  missing  scan  (or  consecutive  missing  scans) 
whose  subsequent  scan  determines  progression,  
the  expected  date  of  
the  
first  missing 
scan  (as  defined  by  the  disease  assessment  schedule)  will  be  used  as  the  date  of 
progression.  
 
10.7 Progression-Free Survival by Central Review 
 
From date of sub-study registration to date of first documentation of progression assessed 
by  central  
review  or  symptomatic  deterioration  
(as  defined  above),  or  death  due  
to  any 
cause.  Patients last known to be alive without report of progression are censored at date 
of  
last  disease  assessment.  For  patients  with  a  missing  scan  (or  consecutive  missing 
scans)  whose  subsequent  scan  determines  progression,  
the  expected  date  of  the  
first 
missing scan (as defined by the disease assessment schedule) will be used as the date of 
progression.  
 
10.8 Duration of Response (DoR) 
 


 
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From date of first documentation of response (CR or PR) to date of first documentation of 
progression assessed by local review or symptomatic deterioration (as defined above), or 
death due to any cause among patients who achieve a response (CR or PR).  Patients 
last 
known  to  be  alive  without  report  of  progression  are  censored  at  date  of  last  disease 
assessment.  For  patients  with  a  missing  scan  (or  consecutive  missing  scans)  whose 
subsequent scan determines progression, the expected date of the first missing scan (as 
defined by the disease assessment schedule) will be used as the date of progression. 
 
 
11.0 STATISTICAL CONSIDERATIONS 
 
11.1 Sample Size with Power Justification 
 
The primary objective is to evaluate the response rate for rucaparib among patients found 
to have LOH or BRCA positive tumors as summarized in Table 1.  
 
Table 1. Eligibility Biomarkers 
Biomarker-positive 
group 
Alteration type 
Eligible alteration 
LOH  
Loss of Heterozygosity (LOH) 
Genomic LOH ≥ 21% 
BRCA  
Homologous Recombination 
Deficiency (HRD) 
Deleterious mutation in 
BRCA1 or 
BRCA2 
 
This study will use the Phase II design implemented 
in biomarker-driven sub-studies within 
Lung-MAP. The study will evaluate rucaparib among patients with tumors defined to meet 
the biomarker eligibility criteria defined in Table 1.  
 
Accrual will be stratified into the cohorts by histology as defined in Section 6.0 (squamous 
and non-squamous histology). The following details pertain to each cohort.  
 
Within  a  cohort, the  accrual  goal  
is  40  eligible and  evaluable patients. Patients  will  be 
considered evaluable if they receive at least one dose of rucaparib. Assuming that 10% of 
patients who are enrolled will be not eligible or evaluable retrospectively, the total accrual 
goal per cohort is 44 patients, for a total of 88 patients in the study.    
 
A design  with  91%  power  and  1-sided  0.05  level  type  I  error  would  require  40 
patients/cohort to rule out an objective response rate (ORR) of 15% or 
less 
if the true ORR 
is 35% or greater.  Calculations were performed using the calculators at 
www.swogstat.org.  
We note that the exact power and type I error are 93% and 6.6%, respectively.   
 
The expected prevalence  of LOH positivity is 16% for Cohort 1 (squamous) and 9% for 
Cohort 2 (non-squamous). The expected prevalence of BRCA 1/2 is 5.8% for squamous 
patients and 1.4% for non-squamous patients.  The estimated percentage of patients with 
both LOH+ and BRCA+ cancers is 0.1% for cohort 1 and 1% for cohort 2 resulting in an 
estimate eligibility rate for the study of 22% for squamous histology NSCLC and 11% for 
non-squamous NSCLC.  
 
Sites are notified of a patient’s sub-study assignment by the SWOG Statistics and Data 
Management Center (SDMC) after the results of the biomarker testing have been reported 
to the SDMC. As described 
in LUNGMAP Section 11.0 (the Lung-MAP screening protocol), 
patients with biomarkers matching only this study will be assigned to this study and sub-
study  assignment  will  be  based  on  randomization  for  patients  eligible  for  multiple 
biomarker-driven  sub-studies.  The  
frequency  of  patients  assigned  
to  
this  sub-study  will 


 
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depend  on  
the  other  biomarker-driven  sub-studies  actively  accruing  while  
this  study  
is 
accruing and could be less than the percentages eligible for the sub-studies. To account 
for this, the estimated percentage of screened patients (with successful biomarker testing) 
assigned to this study is 20% (same for both cohorts).  
 
The expected average monthly accrual rate 
is 4 patients/cohort per month.  We expect the 
rates  to  be  approximately  equal  between  the  cohorts  given  the  history  of  Lung-MAP 
focusing on squamous and abundance of competing studies in non-squamous histology, 
despite the fact that prevalence of squamous histology is about a quarter of all NSCLC. 
The anticipated duration of accrual is 11 months per cohort.  
 
11.2 Analysis Plan 
 
An  
interim  analysis  will  
take  place  when  20  patients/cohort  are  evaluable  
for  
response.  
Evaluability for response is defined based on RECIST 1.1 and accrual is to remain open 
while  patients  are  being  evaluated  for  response.    However,  if  20  or  more  eligible 
patients/cohort  for  the  first  interim  analysis  have  made  it  to  their  second  disease 
assessment and the required number of responses to continue past that interim analysis 
has not been observed, then the accrual to the cohort will be placed in temporary closure 
until the response status for all patients in the interim analysis set is known. 
 
This 
interim analysis will only evaluate early stopping for futility. If 2 or fewer responses are 
observed  (within  a  cohort),  this  will  be  considered  evidence  of  futility  and  the 
recommendation will be to close the cohort for lack of evidence of efficacy of the regimen. 
Interim decisions within a cohort will not affect the outcome of the other cohort.  
 
If the study continues to full accrual, the observation of at least 10 responses within 
a  cohort  will  be  considered  evidence  to  rule  out  the  null  hypothesis of  a  15% 
response rate within that cohort.  
 
Response rates and associated confidence intervals will be calculated. OS, IA-PFS, and 
DoR  will  be  estimated  using  the  method  of  Kaplan-Meier.  The  Brookmeyer-Crowley 
method will be used to calculate confidence intervals for median times. With 40 patients, 
response rates can be estimated within 16% with 95% confidence.  
 
Toxicity  will  be  evaluated  among  all  patients  enrolled  on  the  study  (combining  the 
squamous and non-squamous cohorts).  With 80 patients, any toxicity can be estimated to 
within 11% with 95% confidence. Any toxicity with at least 5% prevalence has at least a 
98% chance of being observed.  
 
Analysis of IA-PFS will take place when 31 IA-PFS events/cohort have been observed. A 
key secondary objective is an assessment of median IA-PFS (mPFS). If the ORR rate is 
less  
than  25%,  but  
the  mPFS  
is  at  
least  4.5  months,  
this  may  be  considered  sufficient 
evidence to continue to the follow-on Phase III.  With 40 patients/cohort this design has 
87% power to rule out a mPFS of 3 months or less, if the true mPFS is 6 months, at the 
0.05  1-sided  
level.  This  
is  based  on  using  Brookmeyer-Crowley  
test  of  null  of  3  month 
mPFS versus alternative of 6 month mPFS with 10 months of accrual and 6 months’ follow-
up. The observation of an mPFS of at least 4.6 months would be considered evidence to 
rule out an mPFS of 3 months or less.  
 
 
12.0 DISCIPLINE REVIEW 
 
12.1 Radiology Review 
 
Central collection is required but review of scans will not be triggered if the study will not 
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scans  will  be  triggered  only  if  deemed  necessary  for  FDA  evaluation.  A  detailed 
description  of  
the  central  
radiology  PFS  
review,  
including  
image  acquisition  parameters 
and image submission instructions, can be found in LUNGMAP Section 18.2f. 
 
a. 
To  ensure  
the  highest  standards  and  consistency  between  different  centers,  all 
scans for disease assessment (baseline, 
interim and end of treatment scans) must 
be  submitted  
to  
the  National  Cancer  
Institute’s  National  Clinical  Trials  Network 
(NCTN)  Imaging  and  RT  Quality  Assurance  Service  Core  (IROC)  in  Ohio  for 
centralized review (see S1900A Section 15.0). 
 
b. 
Centralized review will be  performed  by 3 radiology  experts.  
 The scans will be 
submitted to IROC.  IROC will transmit the scans to the reviewers who will transmit 
the results to the SWOG Statistics and Data Management Center. 
 
c. 
Details of submission of scans to IROC for centralized review and on the central 
review process are listed in S1900A Section 15.0 and LUNGMAP Appendix 18.2. 
 
 
13.0 REGISTRATION GUIDELINES 
 
See Section 13.0 of LUNGMAP for registration guidelines. 
 
In  order  
to  open  Lung-MAP  studies  at  
the  site,  a  separate  Study  Specific  Worksheet  
(SSW)  
is 
required to be submitted to the CIRB for the LUNGMAP screening protocol and each sub-study. 
 
13.1 Registration Timing 
 
Patients must plan to begin treatment within 10 calendar days after sub-study registration. 
 
13.2  Investigator/Site Registration 
 
For investigator/site registration, please refer to Section 13.2 of the LUNGMAP screening 
protocol. In addition, a Delegation Task Log is required for this sub-study.  
 
Delegation Task Log (DTL): 
Each site must complete a protocol-specific Delegation of Tasks Log (DTL) using the DTL 
application  
in  
the  Delegation  Log  section  on  
the  CTSU  members’  website.  The  Clinical 
Investigator  (CI)  
is  required  to  review  and  electronically  sign  the  DTL  prior  to  the  site 
receiving  an  approved  site  registration  status  and  enrolling  patients  to  the  study.  To 
maintain an approved site registration status the CI must re-sign the DTL at least annually 
and  when  a  new  version  of  the  DTL  is  released;  and  activate  new  task  assignments 
requiring CI sign-off. Any 
individual at the enrolling site on a participating roster may 
initiate 
the  site  DTL.  Once  the  DTL  is  submitted  for  CI  approval,  only  the  designated  DTL 
Administrators  or  
the  CI  may  update  
the DTL.  
Instructions  on  completing  
the  DTL  are 
available in the Help Topics button in the DTL application and include a Master Task List, 
which describes DTL task assignments, CI signature, and CTEP registration requirements. 
 
 
14.0 DATA SUBMISSION SCHEDULE 
 
14.1 Data Submission Requirements 
 
Data must be submitted according to the protocol requirements for ALL patients registered, 
whether  or  not  assigned  treatment  is  administered,  including  patients  deemed  to  be 
ineligible.    Patients  for  whom  documentation  is  inadequate  to  determine  eligibility  will 
generally be deemed ineligible. 
 


 
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14.2 Master Forms 
 
Master forms can be found on the protocol page on the CTSU website (www.ctsu.org) and 
(with the exception of the sample consent form and the Registration Worksheet) must be 
submitted on-line via the Web; see S1900A Section 14.3 for details. 
 
14.3 Data Submission Procedures 
 
a. 
Medidata  Rave  is  a  clinical  data  management  system  being  used  for  data 
collection for this trial/study. Access to the trial in Rave is controlled through the 
CTEP-IAM system and role assignments.  
 
b. 
Requirements to access Rave via iMedidata: 
• A valid CTEP-IAM account; and 
• Assigned a Rave role on the LPO or PO roster at the enrolling site of:  
Rave CRA, Rave Read Only, Rave CRA (LabAdmin), Rave SLA, or 
Rave Investigator.  
 
Rave role requirements: 
o Rave CRA or Rave CRA (Lab Admin) role must have a minimum of 
an Associate Plus (AP) registration type; 
o Rave Investigator role must be registered as a Non-Physician 
Investigator (NPIVR) or Investigator (IVR); and   
o Rave Read Only role must have at a minimum an Associates (A) 
registration type.  
 
Refer to https://ctep.cancer.gov/investigatorResources/default.htm for registration 
types and documentation required. 
 
This study has a Delegation of Tasks Log (DTL). Therefore, those requiring write 
access to Rave must also be assigned the appropriate Rave tasks on the DTL. 
 
Upon initial site registration approval for the study in Regulatory Support System 
(RSS), all persons with Rave roles assigned on the appropriate roster will be sent 
a study 
invitation e-mail from 
iMedidata. To accept the 
invitation, site staff must 
log 
in to the Select Login (https://login.imedidata.com/selectlogin) using their CTEP-
IAM username and password, and click on the accept link 
in the upper right-corner 
of the iMedidata page. Site staff will not be able to access the study in Rave until 
all required Medidata and study specific trainings are completed. Trainings will be 
in the form of electronic learnings (eLearnings) and can be accessed by clicking 
on  
the  
link  
in  
the  upper  right  pane  of  
the  
iMedidata  screen. If  an  eLearning  
is 
required and has not yet been taken, the link to the eLearning will appear under 
the study name in iMedidata instead of the Rave EDC link; once the successful 
completion of the eLearning has been recorded, access to the study in Rave will 
be granted, and a Rave EDC link will display under the study name. 
 
Site staff that have not previously activated their iMedidata/Rave account at the 
time of initial site registration approval for the study in RSS will receive a separate 
invitation from iMedidata to activate their account. Account activation instructions 
are 
located on the CTSU website in 
the Data Management section under the Rave 
resource  materials  (Medidata  Account  Activation  and  Study  Invitation 
Acceptance). Additional information on iMedidata/Rave is available on the CTSU 
members’   website in the Data   Management   > Rave section at 
www.ctsu.org/RAVE/ or by contacting the CTSU Help Desk at 1-888/823-5923 or 
by e-mail at mailto:ctsucontact@westat.com. 
 


 
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c. 
You  may  also  access  Rave®  via  the  SWOG  CRA  Workbench via  the  SWOG 
website (www.swog.org).    
 
For difficulties with the CRA Workbench, please email  
technicalquestion@crab.org.  
 
d. 
Institutions  participating  
through  
the  Cancer  Trials  Support Unit  
(CTSU), please 
refer to the CTSU Participation Table. 
 
e. 
Data Quality Portal 
 
The Data Quality Portal (DQP) provides a central location for site staff to manage 
unanswered queries and form delinquencies, monitor data quality and timeliness, 
generate reports, and review metrics.  
 
The DQP 
is 
located on the CTSU members’ website under Data Management. The 
Rave  Home  section  displays  a  table  providing  summary  counts  of  Total 
Delinquencies and Total Queries. DQP Queries, DQP Delinquent Forms and the 
DQP Reports modules are available to access details and reports of unanswered 
queries, delinquent forms, and timeliness reports. Review the DQP modules on a 
regular basis to manage specified queries and delinquent forms. 
 
The DQP is accessible by site staff that are rostered to a site and have access to 
the CTSU website. Staff that have Rave study access can access the Rave study 
data using a direct link on the DQP. 
 
To learn more about DQP use and access, click on the Help icon displayed on the 
Rave Home, DQP Queries, and DQP Delinquent Forms modules. 
 
Note:  Some  Rave  protocols  may  not  have  delinquent  form  details  or  reports 
specified  on  the  DQP.  A  protocol  must  have  the  Calendar  functionality 
implemented 
in Rave by the Lead Protocol Organization (LPO) for delinquent form 
details and reports to be available on the DQP. Site staff should contact the LPO 
Data  Manager  for  their  protocol  regarding  questions  about  Rave  Calendar 
functionality. 
 
14.4 Data Submission Overview and Timepoints  
 
a. 
WITHIN 15 DAYS OF S1900A REGISTRATION, SUBMIT: 
 
 
S1900A Eligibility Criteria Form 
 
S1900A Onstudy Form 
 
If needed, also submit: 
Radiation Therapy Form 
Brain Metastases Form 
 
Smoking Status Assessment Form 
 
Baseline Tumor Assessment Form (RECIST 1.1) 
 
Radiology reports from all scans performed to assess disease at baseline*  
 
If needed, RT summary and/or planning document* 
   
   
   
 


 
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If needed, radiology report from brain CT/MRI* 
 
*(NOTE: Upload reports via the Source Documentation: Baseline form in Rave)  
 
Submit  
to  
IROC  via  TRIAD  
for  Central  Radiology  Review:  
  
Images  
from  scans 
performed to assess disease at baseline as specified in S1900A Section 15.5 
 
b. 
IF PATIENT CONSENTS, SUBMIT SPECIMENS: 
 
Specimens as specified in Section 15.0 S1900A 
 
c. 
WITHIN 15 DAYS AFTER EACH CYCLE (CYCLE = 21 DAYS) OF TREATMENT, 
SUBMIT: 
 
S1900A Treatment Form 
 
S1900A Adverse Event Form* 
 
S1900A Laboratory Values Form  
 
For Cycle 1 only: Submit the S1900A Pre-Treatment Laboratory Values Form. 
 
*For the 
last cycle of treatment, 
include all adverse events occurring within 30 days 
after the last treatment. 
 
d. 
WITHIN 15 DAYS AFTER EVERY DISEASE ASSESSMENT (INCLUDING BOTH 
ON  TREATMENT  AND  OFF PROTOCOL TREATMENT  PRIOR  TO  DISEASE 
PROGRESSION  
(see S1900A Section  9.0 for  Disease  Assessment  Schedule), 
SUBMIT: 
 
Follow-Up  Tumor  Assessment  Form  (RECIST  1.1)  documenting  results  of 
assessment 
 
Radiology reports from all scans performed to assess disease at follow-up (NOTE: 
Upload reports via the Source Documentation: Follow-up form in Rave) 
 
Submit  
to  
IROC  via  TRIAD  
for  Central  Radiology  Review:  
  
Images  
from scans 
performed to assess disease as specified in S1900A Section 15.5. 
 
e. 
WITHIN 15 DAYS OF DISCONTINUATION OF TREATMENT, SUBMIT: 
 
Off Treatment Notice documenting reasons for off protocol treatment 
 
Smoking Status Assessment Form 
 
Forms specified in Section 14.4c. 
 
f. 
ONCE OFF PROTOCOL TREATMENT EVERY 6 MONTHS FOR THE FIRST 2 
YEARS FROM S1900A REGISTRATION, THEN AT THE END OF YEAR 3 FROM 
SUB-STUDY REGISTRATION SUBMIT: 
 
Advanced NSCLC Follow-Up Form 
 
If needed, also submit: 
Radiation Therapy Form 
Brain Metastases Form 
 


 
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Late Adverse Events (if prior to treatment for progression or relapse or a second 
primary, and prior to non-protocol treatment, the patient experiences any severe 
[Grade ≥ 3] adverse event that 
is possibly, probably, or definitely related to protocol 
treatment, or a Serious Adverse Event [SAE] of any grade/attribution, that has not 
been previously reported). 
 
g. 
WITHIN 15 DAYS OF PROGRESSION/RELAPSE, SUBMIT: 
 
Site(s) of Progression or Relapse Form 
 
Follow-Up Tumor Assessment Form (RECIST 1.1) 
 
Radiology reports from all scans performed to assess disease at follow-up (NOTE: 
Upload reports via the Source Documentation: Follow-up form in Rave) 
 
Submit  
to  
IROC  via  TRIAD  
for  Central  Radiology  Review:  
  
Images  
from  scans 
performed to assess disease as specified in S1900A Section 15.5. 
 
h. 
WITHIN 30 DAYS OF KNOWLEDGE OF DEATH: 
 
Submit  
the Notice  of Death documenting death  
information and S1900A End of 
Study  form.    In  addition,  if  the  patient  was  still  on  protocol  treatment,  submit 
materials  specified  in S1900A Section  14.4e or  if  patient  was  no  longer  on 
treatment, submit a final Advanced NSCLC Follow-Up Form. 
 
i. 
Data Submission FOR PATIENTS WHO HAVE PROGRESSED AND WISH TO 
REGISTER TO A NEW SUB-STUDY: 
 
WITHIN 15 DAYS OF PROGRESSION/RELAPSE: 
 
Submit  the  Request  for  New  Sub-Study  Assignment  Form  under the  patient’s 
screening  protocol  (LUNGMAP  or S1400) in  Rave®. Continue  follow-up  on 
S1900A per Section 9.0. See Section 14.0 of the screening protocol for additional 
data submission requirements following request for new sub-study assignment. 
 
j. 
WITHIN 30 DAYS OF MAXIMUM FOLLOW-UP OF 3 YEARS: 
 
S1900A End of Study Form 
 
 
15.0 SPECIAL INSTRUCTIONS 
 
15.1 SWOG Specimen Tracking System (STS) 
 
See LUNGMAP Section 5.1 for SWOG Specimen Tracking System (STS) instructions. 
 
15.2  Translational Medicine and Banking (OPTIONAL FOR PATIENT) 
 
Specimens for translational medicine and banking (submitted to the SWOG Biospecimen 
Bank – Solid Tissue, Myeloma and Lymphoma Division, Lab #201) are considered optional 
for the patient: 
 
a. 
With patient’s consent, specimens must be collected and submitted as follows: 
 
1. 
Buffy Coat and Plasma: 
 
Specimens must be collected at the following times. 


 
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• Pre-study (after consenting and prior to treatment initiation on 
sub-study 
Note:  If  a  patient  provided  buffy  coat  and  plasma for 
LUNGMAP (see Section 15.0 of LUNGMAP) and the blood 
collection  was within  42  days prior  to  the  sub-study 
registration,  
then  no  additional  pre-study  blood  specimen  
is 
required. 
• Weeks 4, 7, and 10 - Patients that go off protocol treatment 
are not required to continue to submit specimens. 
• First progression after study treatment. 
 
Collect approximately 8-10 mL of blood in EDTA tubes. Blood should be 
processed  within  one  hour  after  venipuncture.  If  
immediate  processing 
within this time frame 
is not possible, then refrigerate (4°C) blood in EDTA 
tubes.  The  approximate  time  from  collection  to  processing  should  be 
recorded as part of the patient’s source documentation. EDTA tubes must 
be centrifuged at 800 x g for 10 minutes at 4˚C for the collection of plasma. 
[Note: Sites that do not have a refrigerated centrifuge should spin at room 
temperature  and  ensure  specimens  are  placed  on  
ice  
(regular,  not  dry) 
immediately  after  being  drawn  and  process  rapidly.]  Using  a  pipette, 
transfer  
the  plasma to a 15-mL centrifuge  
tube. Remove  
the  buffy  coat 
layer (thin white or gray layer of cells between the plasma and red blood 
cells) and split between two appropriately labeled 2-mL cryovials.  
 
Spin the plasma in the 15-mL centrifuge tube at 800 x g for an additional 
10 minutes. Avoiding any pelleted material, pipette the plasma into coded 
cryovials at 0.5 ml aliquots. Plasma must be clear before freezing; no cells 
or debris should be present.  
 
Plasma  and  buffy  coat  vials must  be  placed upright in  a -80˚C  
freezer 
immediately after processing to ensure long-term viability.   
 
Frozen plasma and buffy coat specimens should be shipped to the SWOG 
Biospecimen Bank on dry ice. 
 
b. 
Specimen Collection, Submission, and Labeling Instructions 
 
Samples  for  multiple  patients may be  shipped  in  batches to  the  SWOG 
Biospecimen Bank – Solid Tissue, Myeloma and Lymphoma Division, Lab #201, 
at least every 3 months if not more frequently. 
 
For  additional  information  about  labeling  and shipping instructions for  frozen 
plasma  and  buffy  coat  specimens,  refer  to  the  SWOG  Specimen  Submission 
webpage  
(https://www.swog.org/clinical-trials/biospecimen-resources/biospecimen-
processing-and-submission-procedures).  
 
1. 
Liquid specimens must be labeled with the following: 
• SWOG patient number 
• Patient initials 
• Collection date (date the specimen was collected from the patient) 
• Specimen type (e.g. blood, serum, etc.) 
 
c. 
Specimen collection kits are not being provided for this submission; sites must use 
institutional supplies. 
 


 
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15.3 LUNGMAP ctDNA Research Assay – ctDNA  bTMB Peripheral Whole Blood (REQUIRED 
FOR PATIENTS prior to treatment initiation) 
   
   
 
Blood specimens will be collected 
in order to isolate and 
investigate circulating tumor DNA 
(ctDNA) and blood tumor mutational burden (bTMB) – a form of fragmented DNA released 
into patient peripheral circulation specifically from the tumors. Analysis of ctDNA can reveal 
the  presence  of  tumor-specific  mutations  and  other  abnormalities  that  can  serve  as 
biomarkers. The 
information collected will be 
limited to tumor-specific abnormalities known 
or suspected to play roles 
in tumor evolution.  Patient germ-line genetic 
information will not 
be collected. 
 
a. 
Kit Ordering 
 
Immediately after identifying a patient for trial and prior to treatment 
initiation, sites 
must contact Foundation Medicine Inc. – Blood Samples, Lab #232, to order kits 
as follows: 
 
• Call  FMI  Client  Services  at  1-888/988-3639  or  email  request  to 
lung.map@foundationmedicine.com 
• Site must identify itself as a participant in the S1900A SWOG Lung-MAP sub-
study and request the “Lung-MAP ctDNA Clinical Trial Kit.” 
• Reference  the  FMI  Study  ID: FoundationOneLiquidDX-AMC-PRO-20-1496 
and Product ID: FMI-P-020 
• Provide the following information: 
o Treating physician
's name 
o Treating physician
's email address 
o Contact name 
o Contact email address 
o Contact phone 
o Address to which kits should be sent 
o Number of kits needed (one per patient per timepoint) 
 
Kits will arrive within 3 days after ordering (excluding weekends and holidays). 
 
Kits will be gray and white in color, read “Foundation Medicine Clinical Trials Kit,” 
and  and include  four  Roche  Cell-Free  DNA  blood  collection  tubes,  collection 
instructions,  FedEx  return  bags,  and pre-printed  FedEx  airway  bills.  Blood 
collection tubes must be used before their expiration date. 
 
b. 
Timepoints 
 
Collect blood after sub-study registration and prior to treatment initiation. 
 
• Recommended to collect on Cycle 1 Day 1 (prior to treatment) during 
other labs to lessen patients visits. 
 
Note: This is a separate requirement for a ctDNA whole blood specimen 
for all patients registered to S1900A, regardless of whether or not there 
was a ctDNA blood collection for LUNGMAP. 
 
c. 
Specimen Collection and Shipment Instructions 
 
Specimen must be logged via the SWOG Specimen Tracking System. 
 
Step 1: Check special tubes provided in kits to confirm liquid is clear and without 
cloudiness or crystals. 
 


 
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Step 2: Label tubes with date of collection, patient identifiers as requested on the 
included labels (patient data of birth can be added as an extra identifier), 
and sub-study number. 
 
Step 3: Collect four tubes of whole blood (8.5 mL per tube) 
o Prevent backflow: tubes contain chemical additives and it is important 
to avoid backflow into patient 
o Collect specimen by venipuncture 
o Fill tubes completely (8.5 mL per tube) 
 
Step 4: Remove the tube from adapter and immediately mix by gentle inversion 8 
to 10 times. Inadequate or delayed mixing  may result in inaccurate test 
results. One inversion is a complete turn of the wrist, 180
̊ and back, per 
the figure below. 
 
 
 
Step 5: Place specimen into the specimen collection kit. 
o Confirm  each  
tube  
is  
labeled  with  
the  supplied  
labels  
indicating  
the 
date of collection and two unique patient identifiers (label included in 
kit). 
 
Step 6: Select  “Ship  this  Shipment  and  Generate  Packing  List”  in the  SWOG 
Specimen  Tracking  System to  generate  
the  Packing  List. A copy of the 
SWOG Specimen Tracking Packing List must be 
included 
in the shipment. 
Confirm that the tubes are labeled as specified on the Packing List. 
 
Step 7: Preferably on the same day of collection, ship to FMI – Blood Samples, 
Lab  #232 via  FedEx  overnight  delivery  at  ambient  
temperature.  Do  not 
freeze or refrigerate blood samples. Keep at 43-99
̊ F (6-37
̊ C). 
 
FMI  accepts  Saturday  deliveries.  If  shipping  on  a  Friday,  please  overnight 
shipment and mark for Saturday delivery. 
 
d. 
Specimen Usage 
 
Whole blood will be collected from each patient as per collection 
instructions 
in the 
dedicated tubes provided in the LUNGMAP ctDNA Research Kit, and shipped at 
room  temperature  on  the  same  day of  draw,  following  all  indicated  directions 
above. The blood will be processed at FMI; DNA will be extracted and analyzed 
using a hybrid-capture next-generation sequencing approach optimized for ctDNA 
extracted  from  plasma.  Alterations  in  clinically  significant  cancer  genes 
(oncogenes and tumor suppressor genes) will be 
identified and quantitated relative 
to  wild-type  sequences. Tumor-specific  alterations  will  
include  point  mutations, 
small  insertions  and  deletions,  chromosomal  rearrangements  and  copy 
number/amplification events in 311 genes (LUNGMAP ctDNA Research Assay).   
The panel identifies 
chromosomal rearrangements that result 
in oncogenic fusions 
in six genes highly relevant to lung cancer (ALK, EGFR, FGFR3, PDGFRA, RET 
and ROS1). Data reported will 
include the specific base substitutions, 
insertions or 


 
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deletions  at  their  mutant  allele  frequency  (the  proportion  of  mutant  sequences 
relative  to  wild-type  sequences,  a  quantification  of  gene  copy  number 
abnormalities,  and  the  presence  of  fusions,  including  the  fusion  partners  and 
breakpoint  information. The  ctDNA  translational  medicine  proposal  will  be 
submitted as an amendment for CTEP review and approval prior to SDMC review 
of assay results.     
 
The  ctDNA results  are  for  research  purposes  and  will  not  be  shared  with  the 
investigator or patient.  
 
15.4 Specimen Flow Diagram 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lab #211: Foundation Medicine, Inc. (FMI) 
– Tissue Samples 
Test: Screening Biomarker Profiling 
(Required) See LUNGMAP Section 15.2.  
(note: tissue testing may have been performed 
under the legacy S1400 protocol). 
 
Lab #232: Foundation Medicine, Inc. – 
Blood Samples 
 
Test: ctDNA Whole Blood 
(Required) See Section 15.3 
For approved translational medicine 
studies,  
SWOG Biospecimen Bank will forward the 
required specimens  
to the corresponding testing lab. 
Lab #201: SWOG 
Biospecimen Bank – Solid 
Tissue 
 
Banking 
(Optional 
b) 
 
See Section 15.2. 
Screening/Pre-Screening 
Tumor Tissue 
(Required) 
(note: tissue testing may 
have been performed under 
the legacy S1400 protocol). 
See LUNGMAP Section 5.1 
Buffy Coat and 
Plasma (Optional a) 
See Section 15.2. 
a With patient
's consent. 
b Remaining tissue will be sent to the SWOG Biospecimen Bank -Solid Tissue, Myeloma and 
Lymphoma Division, Lab #201, for use of the Translational Medicine studies within any sub-study the 
patient is enrolled in. SWOG Biospecimen Bank will prepare and ship the required specimens to the 
appropriate laboratory. The specimen will be kept until there are no additional sub-studies for the 
patient to enroll in or the tissue is used up, whichever happens first. With patient’s consent, any 
leftover tissue will remain at the SWOG Biospecimen Bank for future exploratory analysis. 
Site 
ctDNA Whole Blood 
(Required) 
See  
Section 15.3. 


 
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15.5 
Radiology Review (REQUIRED) 
 
CT,  PET/CT,  and/or  MRI  
images  must  be  
locally  
read  and  
interpreted  by  
the  
local  site 
radiology service.  Imaging exams must then be submitted to the Imaging and Radiation 
Oncology Core (IROC) at Ohio via TRIAD Imaging Submission procedures for central data 
collection and quality control (QC) check as well as retrospective central review. 
 
a. 
CT,  PET/CT,  and/or  MRI  
images  must  be  submitted  to  IROC  Ohio  for central 
review at the timepoints specified in Section 7.1. 
 
All study participants must have a CT (or MR or PET/CT) exam prior to sub-study 
entry.  Participants  must  then  undergo  additional  imaging  at  the  timepoints 
specified in Section 7.1 until progression of disease.  The same imaging modality 
used for the pre-treatment exam must be used for the post-treatment exams (see 
LUNGMAP Section 10.1). Each exam should be performed per Appendix 18.2 of 
LUNGMAP.  IROC will perform a QC of the imaging exams.   
 
Clinical  management  and  treatment  decisions  will  be  made  by  the  treating 
physician  based  on  local  site  assessments  and  other  clinical  appropriate 
considerations. 
 
Central review of scans will not be triggered 
if the study will not be submitted to the 
FDA for FDA approval of the investigational therapy.  Central review of scans will 
be triggered only if deemed necessary for FDA evaluation.  A detailed description 
of the central radiology PFS review, including image acquisition parameters and 
image submission instructions, can be found in Appendix 18.2 of LUNGMAP. 
 
b. 
TRIAD Digital Image Submission  
 
Transfer  of  Images  and  Data  (TRIAD) is  the  American  College  of  Radiology’s 
(ACR) image exchange application.  TRIAD provides sites participating in clinical 
trials a secure method to transmit images. TRIAD anonymizes and validates the 
images as they are transferred. 
 
TRIAD Access Requirements: 
 
• A valid CTEP-IAM account (see LUNGMAP Section 13.2). 
• Registration and  Credential  Repository  (RCR)  registration  type  of: 
Associate (A), Associate Plus (AP), Non-Physician Investigator (NPIVR), 
or  Investigator  (IVR)  registration  type.  Refer  to  the CTEP Registration 
Procedures  section  for  instructions  on  how  to  request  a  CTEP-IAM 
account and complete registration in RCR. 
• TRIAD Site User role on an NCTN or ETCTN roster. 
All individuals on the Imaging and Radiation Oncology Core provider roster have 
access  to  TRIAD  and  may  submit  images  for  credentialing  purposes,  or  for 
enrollments to which the provider is linked in OPEN. 
 
TRIAD Installations: 
 
To  submit  
images,  
the  
individual  holding  
the  TRIAD  Site  User  
role  will  need  
to 
install the  TRIAD  application  on their workstation. TRIAD  installation 
documentation is available at:  
https://triadinstall.acr.org/triadclient/.     
 
This  process  can  be  done  
in  parallel  
to  obtaining  your  CTEP-IAM  account and 
RCR registration. 
 


 
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For questions, contact    TRIAD Technical  Support  staff  via  email TRIAD-
Support@acr.org or 1-703-390-9858. 
 
 
16.0 ETHICAL AND REGULATORY CONSIDERATIONS 
 
The following must be observed to comply with Food and Drug Administration regulations for the 
conduct and monitoring of clinical investigations; they also represent sound research practice. 
 
Informed Consent 
 
The  principles  of  informed  consent  are  described  by  Federal  Regulatory  Guidelines  (Federal 
Register Vol. 46, No. 17, January 27, 1981, part 50) and the Office for Protection from Research 
Risks Reports:  Protection of Human Subjects (Code of Federal Regulations 45 CFR 46).  They 
must  be  followed  to  comply  with  FDA  regulations  for  the  conduct  and  monitoring  of  clinical 
investigations. 
 
Institutional Review 
 
This study must be approved by an appropriate 
institutional review committee as defined by Federal 
Regulatory Guidelines (Ref. Federal Register Vol. 46, No. 17, January 27, 1981, part 56) and the 
Office for Protection from Research Risks Reports:  Protection of Human Subjects (Code of Federal 
Regulations 45 CFR 46.  
 
Drug Accountability 
 
An investigator is required to maintain adequate records of the disposition of investigational drugs 
according  to  procedures  and  requirements  governing  the  use  of investigational  new  drugs  as 
described in the Code of Federal Regulations 21 CFR 312 and the CTEP Investigator’s Handbook. 
 
Publication and Industry Contact 
 
The  agents  supplied  by  CTEP,  DCTD,  NCI  used  
in  
this  protocol  are  provided  
to  
the  NCI  under 
Collaborative  Agreements  (CRADA,  CTA,  CSA)  between  the  Pharmaceutical  Companies 
(hereinafter  referred  to  as  "Collaborators")  and  the  NCI  Division  of  Cancer  Treatment  and 
Diagnosis.    Therefore,  the  following  obligations/guidelines  in  addition  to  the  provisions  in the 
"Intellectual Property Option to Collaborator"  
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm)  contained  within  the 
terms of award apply to the use of the Agents in this study: 
 
a. 
Agents may not be used for any purpose outside the scope of this protocol, nor can Agents 
be transferred or licensed to any party not participating in the clinical study.  Collaborators 
data for Agents are confidential and proprietary to Collaborators and shall be maintained 
as such by the investigators.  The protocol documents for studies utilizing Agents contain 
confidential information and should not be shared or distributed without the permission of 
the NCI.  If a copy  of this  protocol is requested by a  patient  or patient’s family  member 
participating on the study, the 
individual should sign a confidentiality agreement. A suitable 
model agreement can be downloaded from: http://ctep.cancer.gov.   
 
b. 
For  a  clinical  protocol  where  
there  
is  an  
investigational  Agent  used  
in  combination  with 
(an)other investigational Agent(s), each the subject of different Collaborative Agreements, 
the access to and use of data by each Collaborator shall be as follows (data pertaining to 
such combination use shall hereinafter be referred to as "Multi-Party Data"): 
 
1. 
NCI will provide all Collaborators with written notice regarding the existence and 
nature of any agreements governing their collaboration with NCI, the design of the 


 
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proposed combination protocol, and the existence of any obligations which would 
tend to restrict NCI
's participation in the proposed combination protocol. 
 
2. 
Each Collaborator shall agree to permit use of the Multi-Party Data from the clinical 
trial by any other Collaborator solely to the extent necessary to allow said other 
Collaborator  to  develop,  obtain  regulatory  approval  or  commercialize  its  own 
investigational Agent. 
 
3. 
Any Collaborator having the right to use the Multi-Party Data from these trials must 
agree in writing prior to the commencement of the trials that it will use the Multi-
Party Data solely for development, regulatory approval, and commercialization of 
its own Agent. 
 
c. 
Clinical Trial Data and Results and Raw Data developed under a Collaborative Agreement 
will be made available exclusively to Collaborators, the NCI, and the FDA, as appropriate 
and unless additional disclosure is required by law or court order as described in the IP 
Option to Collaborator 
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm).  Additionally, all 
Clinical Data and Results and Raw Data will be collected, used and disclosed consistent 
with all applicable federal statutes and regulations for the protection of human subjects, 
including,  if  applicable, the Standards  for  Privacy  of  Individually  Identifiable  Health 
Information set forth in 45 C.F.R. Part 164. 
 
d. 
When a Collaborator wishes to initiate a data request, the request should first be sent to 
the NCI,  who will then notify the appropriate investigators (Group Chair for Cooperative 
Group studies, or PI for other studies) of Collaborator
's wish to contact them. 
 
e. 
Any data provided to the Collaborators for Phase III studies must be in accordance with 
the guidelines and policies of the responsible Data Monitoring Committee (DMC), if there 
is a DMC for this clinical trial. 
 
f. 
Any manuscripts reporting the results of this clinical trial must be provided to CTEP by the 
Group  office  for  Cooperative  Group  studies  or  by  the  principal  investigator  for  non-
Cooperative Group studies for 
immediate delivery to Collaborators for advisory review and 
comment prior to submission for publication.  Collaborators will have 30 days from the date 
of receipt for review.  Collaborator shall have the right to request that publication be delayed 
for  up  to  an  additional  30  days  
in  order  to  ensure  that  Collaborator
's  confidential  and 
proprietary data, in addition to the Collaborator’s intellectual property rights, are protected.  
Copies of abstracts must be provided to CTEP for forwarding to Collaborators for courtesy 
review as soon as possible and preferably at least three (3) days prior to submission, but 
in any case, prior to presentation at the meeting or publication in the proceedings.  Press 
releases and other media presentations must also be forwarded to CTEP prior to release.  
Copies of any manuscript, abstract and/or press release/media presentation should be sent 
to: 
E-mail:  ncicteppubs@mail.nih.gov  
 
The  Regulatory  Affairs  Branch  will  then  distribute  them  to  the  Collaborators.    No 
publication,  manuscript  or  other  form  of  public  disclosure  shall  contain  any  of  the 
Collaborator
's confidential/proprietary information. 
 
Monitoring 
 
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.  Cumulative 
CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are due January 31, 
April 30, July 31 and October 31. 
 
Trial Master File 


 
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This  study is  a potential FDA  
registration study;  
therefore,  all  participating  sites  should  be  FDA 
"inspection ready". This entails maintaining a Trial Master File that includes essential documents 
that  may  be  subject  
to  FDA  oversight.  A  
list  of  essential  documents  
is  available  on  
the  SWOG 
website under QA/Audits, https://swog.org/Visitors/QA/Index.asp.  
 
Confidentiality 
 
Please note that the information contained in this protocol is considered confidential and should 
not be used or shared beyond the purposes of completing protocol requirements until or unless 
additional permission is obtained. 
 
16.1 Adverse Event Reporting Requirements 
 
a. 
Definition and Purpose 
 
Definition:  
  Adverse  event  means  any  untoward  medical  occurrence  associated 
with the use of a drug in humans, whether or not considered drug related. (FDA, 
21 CFR 312.32). See Table 16.1 for definition of a Serious Adverse Event (SAE) 
and reporting requirements. 
 
Adverse event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled 
in the studies as well 
as those who will enroll in future studies using similar agents. Adverse events are 
reported  
in  a  routine  manner  at  scheduled  times  during  a  trial.  (Directions  for 
routine reporting are provided 
in Section 14.0.) Additionally, certain adverse events 
must be reported in an expedited manner to allow for more timely monitoring of 
patient  safety  and  care.  The  following  guidelines  prescribe  expedited  adverse 
event reporting for this protocol.  
 
b. 
Reporting method 
 
This  study  requires  that  expedited  adverse  events  be  reported  to  SWOG 
Operations Office using the Cancer Therapy Evaluation Program Adverse Event 
Reporting  System  (CTEP-AERS).    CTEP’s  guidelines  for  CTEP-AERS  can  be 
found at http://ctep.cancer.gov 
 
NOTE:  For this study, all adverse events requiring expedited reporting must 
initially be reported on the Adverse Event Form in the appropriate Treatment 
Cycle folder in Medidata Rave.  The CTEP-AERS report must then be initiated 
directly from the Adverse Event Form in Medidata Rave.  Do not initiate the 
CTEP-AERS report via the CTEP-AERS website. 
 
c. 
When to report an event in an expedited manner 
 
 Some adverse events require 24-hour notification (refer to Table 16.1) via CTEP-
AERS.  
 
In the rare event when internet connectivity is disrupted a 24-hour notification is 
made to SWOG by telephone at 210-614-8808 or by email adr@swog.org .  An 
electronic  report MUST be  submitted  immediately  upon  re-establishment  of 
internet connection. 
 
When the adverse event requires expedited reporting, submit the report via CTEP-
AERS  within  
the  number  of  calendar  days  of  
learning  of  
the  event  specified  
in 
Table 16.1. 
 


 
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d. 
Other recipients of adverse event reports 
 
The  SWOG  Operations  Office  will  forward  reports  and  documentation  to  the 
appropriate regulatory agencies and drug companies as required. 
 
Adverse  events  determined  to  be  reportable  to  the  Institutional  Review  Board 
responsible for oversight of the patient must be reported according to local policy 
and procedures. 
 
Copies  of  all  adverse  event  
reports  submitted  
to  
the  FDA  should  be  
forwarded 
electronically to CTEPSupportAE@tech-res.com with the protocol number in the 
subject line.  
 
e. 
Expedited reporting for investigational agents 
 
Expedited reporting is required if the patient has received at least one dose of the 
investigational agent(s) as part of the trial. Reporting requirements are provided in 
Table 16.1.  The investigational agent used in this study is rucaparib.   
 
If there is  any question  about the reportability  of  an  adverse event or  
if Internet 
connectivity  is  please  telephone  or  email  the  SAE  Program  Manager  at  the 
Operations Office, 210-614-8808 or adr@swog.org, before preparing the report. 
 
NOTE: For this study, all adverse events requiring expedited reporting must 
initially  be  reported  on  the  Adverse  Event  Form  in  the  appropriated 
Treatment Cycle folder in Medidata Rave.  Once the adverse event is entered 
into RAVE, the Rules Engine will confirm whether or not the adverse event 
requires expedited reporting.  The CTEP-AERS report must then be initiated 
directly from the Adverse Event Form in Medidata Rave.  Do not initiate the 
CTEP-AERS  report  via  the  CTEP-AERS  website.  
  Sites are  encouraged  to 
confirm  the  Expedited  Reporting  Evaluation  Recommendation  with  the 
reporting criteria outlined in Table 16.1. 
 
 
 


 
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Table 16.1: 
Late Phase 2 and Phase 3 Studies:  Expedited Reporting Requirements for Adverse Events that 
Occur  on  Studies  under  a  Non-CTEP  IND  within  30  Days  of  the  Last  Administration  of  the 
Investigational Agent/Intervention rucaparib
1 
 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or not 
they are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
 
 An adverse event is considered serious if it results in ANY of the following outcomes:   
1) Death 
2) A life-threatening adverse event  
3) An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) A congenital anomaly/birth defect.  
6) Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via CTEP-
AERS within the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization  
≥ 24 hrs 
10 Calendar Days 
24-Hour 5 
Calendar Days 
Not resulting in 
Hospitalization  
≥ 24 hrs 
Not required 
10 Calendar Days 
NOTE:  Protocol specific exceptions to expedited reporting of serious adverse events are found in the Specific 
Protocol Exceptions to Expedited Reporting (SPEER) portion of the CAEPR or Section 16.1f.  
Expedited AE reporting timelines are defined as: 
o  
“24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-AERS within 24 hours of 
learning of the AE, followed by a complete expedited report within 5 calendar days of the initial 24-
hour report. 
 
o “10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 calendar 
days of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
 
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
• All Grade 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
• Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization  
• Grade 3 adverse events 
May 5, 2011 
 
 


 
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f. 
Additional  
Instructions  or  Exceptions  
to  CTEP-AERS  Expedited  Reporting 
Requirements for Late Phase 2 and Phase 3 Studies Utilizing an Agent under 
a Non-CTEP-IND: 
 
1. 
Group-specific instructions. 
 
Supporting Documentation Submission – Within 5 calendar days submit 
documentation  supporting  the  CTEP-AERS  report  to  the  SWOG 
Operations Office by fax 210-614-0006. Specific instructions will be sent 
by email to the reporting site by the SAE Program Manager. 
 
2. 
The  adverse  events  listed  below  also  require  expedited  reporting via 
CTEP-AERS for this trial: 
 
• All second and secondary malignancies (See Section 16.1g) 
 
• Any grade of pneumonitis is reportable:  
 
o pneumonitis  
o interstitial lung disease  
o pulmonary fibrosis  
o acute interstitial pneumonitis 
o alveolitis necrotizing 
o alveolitis 
o hypersensitivity pneumonitis 
o organizing pneumonia 
 
g. 
Reporting Secondary Malignancy, including AML/ALL/MDS 
 
1. 
A secondary malignancy is a cancer caused by treatment for a previous 
malignancy  (e.g.,  treatment  with  investigational  agent/intervention, 
radiation or chemotherapy).  A secondary malignancy is not considered a 
metastasis of the initial neoplasm. 
 
SWOG requires all secondary malignancies that occur following treatment 
with an agent under a Non-NCI IND to be reported via CTEP-AERS.  Three 
options are available to describe the event. 
 
• Leukemia  secondary  to  oncology  chemotherapy  (e.g.,  Acute 
Myelocytic Leukemia [AML]) 
 
• Myelodysplastic syndrome (MDS) 
 
• Treatment-related secondary malignancy 
 
Any malignancy possibly related to cancer treatment (including AML/MDS) 
should also be reported via the routine reporting mechanisms outlined in 
each protocol. 
 
A  second  malignancy  is  one  unrelated  to  the  treatment  of  a prior 
malignancy (and is NOT a metastasis from the 
initial malignancy). For this 
protocol, second malignancies also require expedited reporting via CTEP-
AERS.  
 
For more information see: 


 
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http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/
aeguidelines.pdf  
 
2. 
Supporting  documentation  should  be  submitted  
to  CTEP  
in accordance 
with  instructions  provided  by  the  CTEP-AERS  system.    Supporting 
documentation must also be submitted to SWOG Operations Office by fax 
to 210-614-0006. 
 
NOTE: If a patient has been enrolled in more than one NCI-sponsored 
study, the report must be submitted for the most recent trial. 
 
h. 
Reporting Serious Adverse Events to Clovis 
 
SWOG Operations will forward reports of all serious adverse events and events of 
overdose  
(defined  as  any  dose  above  
the  protocol-specified  dose  of rucaparib) 
associated with an SAE within 24 hours of NCI/CTEP receipt of serious adverse 
event documentation from the study site.  
 
i. 
Reporting Pregnancy, Pregnancy Loss, and Death Neonatal 
 
1. 
Pregnancy Study participants who become pregnant while on study; that 
pregnancy should be reported in an expedited  manner via CTEP-AERS 
as Grade 3 “Pregnancy, puerperium and perinatal conditions – Other 
(pregnancy)” under  the Pregnancy,  puerperium  and  perinatal 
conditions SOC.   
 
Additionally,  the  pregnancy  outcome  for  patients  on  study  should  be 
reported  via  CTEP-AERS  at  the  time  the  outcome  becomes  known, 
accompanied  by  the  same  Pregnancy  Report  Form  used  for  the  
initial 
report. 
 
2. 
Pregnancy  Loss   Pregnancy  loss  is  defined  in  CTCAE  as  “Death  in 
utero.”  Pregnancy  loss  should  be  reported  expeditiously  as Grade  4 
“Pregnancy  loss”  under  the  Pregnancy,  puerperium  and  perinatal 
conditions SOC.   
 
A Pregnancy loss should NOT be reported as a Grade 5 event under the 
Pregnancy, puerperium and perinatal conditions SOC, as currently CTEP-
AERS recognizes this event as a patient death. 
 
3. 
Death Neonatal  Death neonatal 
is defined 
in CTCAE as “Newborn death 
occurring during the first 28 days after birth  A neonatal death should be 
reported expeditiously as Grade 4 “Death neonatal” under the General 
disorders and administration SOC. 
 
Neonatal  death  should NOT be  
reported  as  a  Grade  5  event  under  
the 
General  disorders  and  administration  SOC  as  currently  CTEP-AERS 
recognizes this event as a patient death. 
 
 


 
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NOTE:  When submitting CTEP-AERS reports for “Pregnancy, “Pregnancy loss”, 
or “Neonatal 
loss”, the Pregnancy Information Form should also be completed and 
faxed with any additional medical information to 210-614-0006.  The potential risk 
of exposure of the fetus to the investigational agent(s) or chemotherapy agent(s) 
should be  documented  
in the “Description  of Event” section  of the CTEP-AERS 
report.  
 
The Pregnancy Information Form is available at:  
http://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm.  
 
 


 
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17.0 BIBLIOGRAPHY 
 
1  
Curtin,  N.J., Inhibiting  
the  DNA  damage  response  as  a  
therapeutic  manoeuvre  
in  cancer. Br  J 
Pharmacol 169(8): p. 1745-65, 2013. 
 
2  
Broustas, C.G., Lieberman, H. B., DNA Damage Response Genes and the Development of Cancer 
Metastasis. Radiat Res. 181 (2): 111-130, 2014. PMCID: PMC4064942 
 
3  
Swisher,  E.M.,  et  al., Rucaparib  in  relapsed,  platinum-sensitive  high-grade  ovarian  carcinoma 
(ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 18(1): p. 75-
87, 2017. 
 
4  
Mateo, J., et al., DNA repair defects and olaparib in metastatic prostate cancer. NEJM, 2015. 
 
5  
Shroff, R., et  al., Rucaparib  monotherapy  in  patients  with  pancreatic  cancer  and  a  known 
deleterious BRCA mutation. JCO-Precision Oncology, 2018. 
 
6  
Owonikoko, T.K., et al., A systematic analysis of efficacy of second-line chemotherapy in sensitive 
and refractory small-cell lung cancer. J Thorac Oncol 7(5): p. 866-72, 2012. 
 
7  
Fung-Kee-Fung,  M.,  et  al., Optimal  chemotherapy  treatment  for  women  with  recurrent  ovarian 
cancer. Curr Oncol 14(5): p. 195-208, 2007. 
 
8  
Giaccone, G., et al., Teniposide in the treatment of small-cell lung cancer: the influence of prior 
chemotherapy. J Clin Oncol 6(8): p. 1264-70, 1988. 
 
9  
Ledermann, J., et al., Olaparib maintenance therapy in patients with platinum-sensitive relapsed 
serous  ovarian  cancer:  a  preplanned  retrospective  analysis  of  outcomes  by  BRCA  status  
in  a 
randomised phase 2 trial. Lancet Oncol 15(8): p. 852-61, 2014. 
 
10  
Fong, P.C., et al., Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA 
carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol 28(15): p. 2512-9, 2010. 
 
11  
Mazzoni,  F.,  et  al.,  From  clinical  
trials  
to  clinical  practice:  predictors  of  response  
to  erlotinib  
in 
advanced non-small cell lung cancer patients pretreated with chemotherapy. Tumori 97(2): p. 160-
5, 2011. 
 
12  
Swisher,  E.M.,  et  al.,  Rucaparib  in  relapsed,  platinum-sensitive  high-grade  ovarian  carcinoma 
(ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 18(1): p. 75-
87, 2017. 
 
13  
Mazzoni,  F.,  et  al.,  From  clinical  
trials  
to  clinical  practice:  predictors  of  response  
to  erlotinib  
in 
advanced non-small cell lung cancer patients pretreated with chemotherapy. Tumori 97(2): p. 160-
5, 2011. 
 
14  
Coleman,  R.L.,  et  al.,  Rucaparib  maintenance  treatment  for  recurrent  ovarian  carcinoma  after 
response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 
trial. Lancet 390(10106): p. 1949-1961, 2017. 
 
15  
Plummer,  R.,  et  al.,  Phase  1  dose-escalation  study  of  the  PARP  inhibitor  CEP-9722  as 
monotherapy or 
in combination with temozolomide 
in patients with solid tumors. Cancer Chemother 
Pharmacol 74(2): p. 257-65, 2014. 
 


 
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16  
Plummer,  R.,  et  al.,  A  phase  II  study  of  the  potent  PARP  inhibitor,  Rucaparib  (PF-01367338, 
AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of 
chemopotentiation. Cancer Chemother Pharmacol 71(5): p. 1191-9, 2013. 
 
17  
Wilson,  R.H.,  et  al.,  A  phase  I  study  of  intravenous  and  oral  rucaparib  in  combination  with 
chemotherapy in patients with advanced solid tumours. Br J Cancer 116(7): p. 884-892, 2017. 
 
18  
Kristeleit,  R.,  et  al.,  A  Phase  I-II  Study  of  the  Oral  PARP  Inhibitor  Rucaparib  in  Patients  with 
Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res 23(15): 
p. 4095-4106, 2017. 
 
19  
Swisher,  E.M.,  et  al.,  Rucaparib  in  relapsed, platinum-sensitive  high-grade  ovarian  carcinoma 
(ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 18(1): p. 75-
87, 2017. 
 
20  
Coleman,  R.L.,  et  al.,  Rucaparib  maintenance  treatment  for  recurrent  ovarian  carcinoma  after 
response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 
trial. Lancet 390(10106): p. 1949-1961, 2017. 
 
21  
Oza  AM,  Tinker  AV,  Oaknin  A,  Shapira-Frommer  R,  McNeish  
IA,  Swisher  EM,  et  al.  Antitumor 
activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma 
and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 
and ARIEL2. Gynecol Oncol, 2017. 
 
22  
Coleman,  R.L.,  et  al.,  Rucaparib  maintenance  treatment  for  recurrent  ovarian  carcinoma  after 
response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 
trial. Lancet 390(10106): p. 1949-1961, 2017. 
 
23  
Oza  AM,  Tinker  AV,  Oaknin  A,  Shapira-Frommer  R,  McNeish  
IA,  Swisher EM,  et  al.  Antitumor 
activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma 
and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 
and ARIEL2. Gynecol Oncol, 2017. 
 
24  
Coleman,  R.L.,  et  al.,  Rucaparib  maintenance  treatment  for  recurrent  ovarian  carcinoma  after 
response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 
trial. Lancet 390(10106): p. 1949-1961, 2017. 
 
25  
Oza  AM,  Tinker  AV, Oaknin  A,  Shapira-Frommer  R,  McNeish  
IA,  Swisher  EM,  et  al.  Antitumor 
activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma 
and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 
and ARIEL2. Gynecol Oncol, 2017. 
26  
Fulcher N, Shenolikar RA, Durden E, Moore KN, editors. Incidence of secondary myelodysplastic 
syndrome  and  acute  myeloid  
leukemia  
in  patients  with  ovarian  and  breast  cancer  
in  
real-world 
setting in the U.S. 2017 ASCO Annual Meeting: J Clin Oncol 35 (suppl; abstr 5574), 2017. 
 
27  
Friedenson  B.  The  BRCA1/2  pathway  prevents  hematologic  cancers  
in  addition  to  breast  and 
ovarian cancers. BMC Cancer 7:152, 2007. 
 
28  
Eisenhauer,  E.,  Therasse,  P.,  Bogaerts,  J.,  Schwartz,  L.,  Sargent,  D.,  Ford,  R.,  …  Verweij,  J. 
(2009). New response evaluation criteria 
in solid tumours: Revised RECIST guideline (version 1.1). 
European Journal of Cancer, 45(2), 228–247. doi: 10.1016/j.ejca.2008.10.026 
 


 
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18.0 APPENDIX 
 
18.1 
New York Association Classification 
 
18.2 
Monitoring Plan 
 
18.3 Instructions for the SWOG Biospecimen Bank 
 
18.4 Investigational Product Incident Report Form 
18.5 Examples of Cytochrome (CYP) Substrates 
18.6 Intake Calendar – Rucaparib 
18.7 Patient Drug Information Handout and Wallet Card 
 
 
 
 
 


 
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18.1 New York Heart Association Classification 
 
 
 
 
Need for 
Physical Ability    
Class 
Cardiac Symptoms 
Limitations 
Additional Rest* 
To Work**   
 
 
 
I 
None 
None 
None 
Full Time 
 
II 
Only moderate 
Slight 
Usually only slight 
Usually full time 
   
    
or occasional 
 
III 
Defined, with less 
Marked 
Usually moderate 
Usually part time 
 
than ordinary 
 
activity 
 
IV 
May be present 
Extreme 
Marked 
Unable to work 
 
even at rest, & any 
 
activity increases 
 
discomfort 
 
* 
To control or relieve symptoms, as determined by the patient, rather than as advised by 
the physician. 
** 
At accustomed occupation or usual tasks. 
 
 


 
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18.2 Monitoring Plan 
 
For information on the LUNGMAP Monitoring Plan, please refer to LUNGMAP Appendix 
18.2. 
 
 
 
 
 
 
 


 
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18.3 Instructions for the SWOG Biospecimen Bank 
 
Frozen Plasma and Buffy Coat 
The SWOG Biospecimen Bank will receive frozen plasma and buffy coat at up to 5 time 
points per patient. Upon receipt, the Bank will accession, barcode, and Bank specimens 
in a -80°C freezer.   
 
Formalin-fixed Paraffin-Embedded (FFPE) Tissue 
The SWOG Biospecimen Bank will receive FFPE specimens as either blocks or 
slides/sections at up to 1 timepoint per patient. Upon receipt, the Bank will accession, 
barcode, and Bank specimens at ambient temperature.   
 
At the end of the study, the Bank will receive notification from the SWOG Statistics and 
Data Management Center to distribute specimens for testing.   
 
 
 


 
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18.4 Investigational Product Incident Report Form 
 
For  information  on  rucaparib  storage  temperature  excursion,  please  refer  to S1900A 
Section  3.1 and submit  this  form to  Clovis  within  24  hours  after  becoming  aware  of 
excursion and prior to dosing. 
 
 


 
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Investigator Initiated Trial Information 
IIT Number: 
 
Investigator:  
Site Number, if 
applicable:  
 
Site Country:  
Study Staff Name:   
Title: 
 
Email:   
Tel:   
Report Date: 
 
Investigational Product Incident Summary 
IP Name: 
Active IP Dosage Form and  Strength: 
Placebo Dosage Form and  Strength: 
rucaparib tablets
     
200mg   250mg    300mg    
200mg      250mg    300mg    
Lot No(s): (i.e H02288A1) 
IP Type: 
(ex: bottle, blister, vial)   Bottle 
Select type of incident: temperature excursion, lost IP, damaged IP, miscount, or other. Complete one form for each incident. 
  Lost IP / Damaged Shipment (Shipment # if applicable:_________________)                Damaged IP        
 
Miscount   
  over-filled     under-filled                                Other:_____________________________          
Patient ID: 
Visit Cycle # 
Patient’s Current Dose:  
 
Frequency: 
Patient Next Visit Date (DD-MMM-YYYY):  
 
Date Patient Reported incident to the Site (DD-MMM-YYYY):  
 
Please indicate number of IP tablets/bottles/etc. that were affected:  
 
Did patient miss any doses?  
If yes, please ensure the patient recorded the missed dose in their patient diary, if applicable.  
  Yes            No 
Do you need urgent resupply due to this event? 
  Yes            No 
Did you attach accompanying documents and/or photos?  
  Yes            No 
  Temperature Excursion                                                         
Please complete below table for summary of excursion and explanation of event.  Check  appropriate boxes. 
Excursion  
Date 
(DD-MMM-YYYY) 
Minimum 
Excursion 
Temperature 
Maximum 
Excursion 
Temperature 
Excursion  
Duration  
(hours) 
Temperature  
Log 
Attached? 
Was the IP previously involved in 
another temperature excursion?  
If yes, please provide date. 
 
        
oC   oF  
       
oC  oF                   
  
Yes   No Yes   No 
(DD-MMM-YYYY) 
Comments:   
 
                                                                                                                                                             
                                                         
                                                                                                      
                                         N/A  (if no additional comments)                        


 
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Signature: ______________________________________________________ 
 
Date: __________________ 
 
Email this form to RucaSupply@clovisoncology.com (preferred)  
or Fax to + 1 415 276 5777 
THIS SECTION IS TO BE COMPLETED BY CLOVIS PERSONNEL ONLY  
Clovis Comment: 
 
 
 
Clovis Review Name & Title: 
Clovis Signature: _________________________________________________  
Date: ___________________ 
 
 
 
 


 
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18.5 Examples of Cytochrome (CYP) Substrates 
 
See Section 7.2 for precautions.  
 
Because 
lists of these agents are constantly changing, it is important to regularly consult a 
frequently-updated  
list  
for  
the  most up-to-date  
listing  of  agents;  medical  
reference  
texts 
such as the Physicians’ Desk Reference may also provide this information. 
 
Please  consult  the “Drug  Development  and  Drug  Interactions:  Table  of  Substrates, 
Inhibitors and Inducers,” which can be found on the U.S. Food and Drug Administration 
website  at  See  
the  
following  FDA  
links  
for  additional  examples  of  sensitive  substrates. 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugI
nteractionsLabeling/ucm093664.htm    
 
 
 
 
 


 
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18.6 Intake Calendar – Rucaparib SWOG Study: S1900A 
 
Site Personnel Instructions 
 
• Patient number should be recorded on the bottle label in the spaces provided by 
site personnel at the time of assignment to patient. 
 
• Ensure that patient clearly understands the guidelines for self-medication. 
 
• Patient should be given enough supply to last until their next study visit. 
 
• Unused drug and/or empty bottles should be returned to the site at the next study 
visit. 
 
• A new Intake Calendar must be given to a patient with a change in dose or tablet 
strength.  Re-educate the patient regarding their dose schedule as stated below. 
 
• It is recommended that sites contact the patient/caregiver by telephone to confirm 
dosage adherence  in  the  first  few  days  of  Cycle  1 and  during  the  first  cycle 
following any tablet strength change. 
 
Please review the following with the patient: 
 
• Cycle, Start Date and Start Time information with the patient. If possible, have the 
patient document their first dose in the appropriate calendar box. 
 
• Patient’s dose schedule: Rucaparib should be taken twice a day, as close to the 
same time each day as possible. Provide patient with the instructions on how to 
document this schedule appropriately. 
 
Include on the Intake Calendar and review with the patient: dosage, strength 
of tablets provided, quantity to take at each dose, and tablet description (i.e. 
blue, round tablet).   
 
Verify  that  the  tablet  strength  listed  on  the  bottle  label  matches  the 
instructions provided to the patient. 
 
Tell the patient what the tablets will look like based on the strength provided: 
o 200 mg tablets: blue, round shaped tablets, marked with “C2” 
o 250 mg tablets: white, diamond shaped tablets, marked with “C25” 
o 300 mg tablets: yellow, oval shaped tablets, marked with “C3” 
 
• Rucaparib can be taken with or without food.  
 
• How  to  document  vomited,  missed, or  skipped  doses  in  the  specific  areas 
provided. 
 
 


 
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SWOG Study: S1900A 
 
 
Cycle: __________ 
Start Date: __________ 
      Start Day (circle one): Sun  M  Tu  W  Th  F  Sat 
 
 
 
Instructions for the patient: 
This is a 21-day cycle calendar on which you are to record the number of rucaparib tablets you take 
each day. You should: 
• Take rucaparib 2 times a day at the same time of day as close to 12 hours apart as possible, 
unless otherwise instructed.  
• Take rucaparib with at least 8 oz. (240 mL) of room temperature water with or without food. 
• Put the date in the box on the calendar and note the time of both doses for each day.  
• Check off if the dose was taken or not 
• Swallow the tablet whole; do not chew them prior to swallowing.  
• Document any changes to taking the doses in the comments section provided below 
 If you miss a dose, take your next dose at your usual scheduled time.  Do not take an extra 
dose to make up for a missed dose. 
 If you vomit a dose, do not take an extra dose. Take your next dose at your usual scheduled 
time. 
 If you take too much of rucaparib, call your site personnel listed below. 
 If you develop any side effects, mark this on the calendar on the day you note 
the effect. Contact site personnel listed below. 
• Take medication as directed by study doctor. 
 
Storage: 
Store rucaparib tablets should be stored at room temperature (between 15 ºC and 30ºC) in their original 
container. Keep the medication in their bottles: do not transfer to any other container or share your 
medication with anyone.  Keep out of the reach of children and pets. 
 
Your dose is:  ________________________ (example: 600mg twice daily)    
You should take:  ______ (number of pills) _________ mg (example: 300 mg, 200 mg or 250 mg). 
Description of tablet: ______________________ (i.e. blue, round tablet)  
 
 
If you have questions, contact: _________________________    Telephone: ______________________ 
Special Instructions:  
 
Date 
Was dose taken? 
What time? 
# tablets taken (tablet 
strength) 
Comments 
Example 
1st dose: 
 
    8   :   00  am/pm 
    8   :   00  am/pm 
 
1st dose:   2 (300 mg)    . 
 2nd dose:   2 (300 mg)   . 
 
 Yes 
□ No 
2nd dose: 
 
 Yes 
□ No 
Day1    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
 ____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
 


 
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Date 
Was dose taken? 
What time? 
# tablets taken (tablet 
strength) 
Comments 
Example 
1st dose: 
 
    8   :   00  am/pm 
    8   :   00  am/pm 
 
1st dose:   2 (300 mg)    . 
 2nd dose:   2 (300 mg)   . 
 
 Yes 
□ No 
2nd dose: 
 
 Yes 
□ No 
Day2    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 3    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 4    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 5    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 6    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 7    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 8    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 9    
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 10   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 11   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
 
 


 
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Date 
Was dose taken? 
What time? 
# tablets taken (tablet 
strength) 
Comments 
Example 
1st dose: 
 
    8   :   00  am/pm 
    8   :   00  am/pm 
 
1st dose:   2 (300 mg)    . 
 2nd dose:   2 (300 mg)   . 
 
 Yes 
□ No 
2nd dose: 
 
 Yes 
□ No 
Day 12   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 13   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 14   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 15   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
 ____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 16   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 17   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
 ____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 18   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 19   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 20   
____/____/____ 
1st dose: 
 
 ____:____am/pm 
 ____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
Day 21 
____/____/____ 
1st dose: 
 
 ____:____am/pm 
____:____am/pm 
 1st dose: ____________ 
 
 2nd dose:____________    
 
□ Yes 
□ No 
2nd dose: 
 
□ Yes 
□ No 
 
 
 


 
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18.7  PATIENT DRUG INFORMATION HANDOUT AND WALLET CARD 
 
Information for Patients, Their Caregivers and Non-Study Healthcare Team on Possible 
Interactions with Other Drugs and Herbal Supplements  
The patient ____________________________ is enrolled on a clinical trial using the experimental study 
drug, Rucaparib. This clinical trial is sponsored by SWOG.  This form is addressed to the patient but 
includes important information for others who care for this patient.  
 
These are the things that you as a healthcare provider need to know: 
 Rucaparib interacts with certain specific enzymes in your liver, certain transport proteins that help move 
drugs in and out of cells.  These enzymes and transport proteins may interact with over-the-counter, 
herbal, and prescriptions medications. 
• The enzymes in question are CYP1A2, CYP2C9, CYP2C19, and CYP3A.  Rucaparib blocks drugs 
that need these enzymes to break down further in the liver.  Co-administration of rucaparib with drugs 
that are CYP1A2, CYP2C9, CYP2C19, and CYP3A substrates may increase risks of toxicities of 
these drugs. 
• Rucaparib also inhibits the function of MATE1, MATE2-K, and OCT1, which are proteins that move 
drugs in and out of cells/organ. Co-administration of rucaparib with drugs that are substrates of these 
transport proteins may increase risks of toxicities of these drugs. 
 
To the patient: Take this paper with you to your medical appointments and keep the attached 
information card in your wallet.   
Rucaparib may interact with other drugs which can cause side effects. For this reason, it is very important 
to tell your study doctors of any medicines you are taking before you enroll onto this clinical trial.  It is also 
very important to tell your doctors if you stop taking any regular medicines, or if you start taking a new 
medicine while you take part in this study.  When you talk about your current medications with your 
doctors, include medicine you buy without a prescription (over-the-counter remedy), or any herbal 
supplements such as St. John’s Wort.  It is helpful to bring your medication bottles or an updated 
medication list with you. 
 
Many health care providers can write prescriptions.  You must tell all your health care providers (doctors, 
physician assistants, nurse practitioners, pharmacists) you are taking part in a clinical trial.  
 
These are the things that you and they need to know:  
 
Rucaparib must be used very carefully with other medicines that use certain liver enzymes or transport 
proteins to be effective or to be cleared from your system.  Before you enroll onto the clinical trial, your 
study doctor will work with your regular health care providers to review any medicines and herbal 
supplements that are considered “strong inducers/inhibitors or substrates” of CYP450, transport proteins 
MATE1, MATE2-K, and OCT1.  These characteristics may change how rucaparib or other medicine 
works in your body. 
 
• Please be very careful!  Over-the-counter drugs (including herbal supplements) may contain 
ingredients that could interact with your study drug.  Speak to your doctors or pharmacist to 
determine if there could be any side effects.  
 
 


 
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o Prescription drugs such as metformin (for diabetes), digoxin (for heart conditions), or drugs with 
narrow therapeutic window like warfarin (or Coumadin, for blood clots). 
• Your regular health care provider should check a frequently updated medical reference or call your 
study doctor before prescribing any new medicine or discontinuing any medicine.  Your study doctor’s 
name is  
_____________________________________ and he or she can be contacted at  
 
_____________________________________. 
 
 
 


 
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STUDY DRUG INFORMATION WALLET CARD   
You are enrolled on a clinical trial using the experimental study drug 
rucaparib.  This clinical trial is sponsored by the NCI.  Rucaparib 
may interact with drugs that are processed by your liver, or use certain 
transport proteins in your body.  Because of this, it is very important 
to: 
 Tell your doctors if you stop taking any medicines or if you start 
taking any new medicines. 
 Tell all your health care providers (doctors, physician assistants, 
nurse practitioners, or pharmacists) that you are taking part in a 
clinical trial. 
 Check with your doctor or pharmacist whenever you need to use 
an over-the-counter medicine or herbal supplement. 
 
 
 
 
 Rucaparib interacts with specific liver enzymes called CYP1A2, 
CYP2C9/19, and CYP3A, transport proteins (MATE1/2-K, and 
OCT1) and must be used very carefully with medicines that require 
these enzymes and transport proteins.  
 Before prescribing new medicines, your regular health care 
providers should go to a frequently-updated 
medical reference for a list of drugs to avoid, or contact 
your study doctor.   
 Your study doctor’s name is _____________________________ 
and can be contacted at _________________________________.  

ICF_001.pdf: 
Readability Statistics: 
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Flesch-Kincaid Grade Level 8.2 
Version Date 12/14/20 
 
 
 
 
Research Study Informed Consent Document 
 
Study Title for Participants: Targeted Treatment (rucaparib) for Advanced Non-Small 
Cell Lung Cancer 
 
LUNGMAP, “A Master Protocol to Evaluate Biomarker-Driven Therapies and 
Immunotherapies in Previously-Treated Non-Small Cell Lung Cancer (Lung-MAP 
Screening Study)” 
 
Official Study Title for Internet Search on http://www.ClinicalTrials.gov:  
 
S1900A, “A Phase II Study of Rucaparib in Patients with Genomic LOH High And/Or 
Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-Small Cell Lung Cancer 
(Lung-MAP Sub-Study)” 
(NCT 03845296) 
 
Overview and Key Information  
 
What am I being asked to do? 
 
We are asking you to take part in a research study.  We do research studies to try to answer 
questions about how to prevent, diagnose, and treat diseases like cancer. 
 
We are asking you to take part in this research study because you have non-small cell lung 
cancer that has spread outside your lungs, and your tumor sample has a biomarker which is 
positive for LOH (loss of heterozygosity) or BRCA1/2 mutations that matches one of the 
treatment studies that are open.  
 
Taking part in this study is your choice.  
 
You can choose to take part or you can choose not to take part in this study.  You also can 
change your mind at any time.  Whatever choice you make, you will not lose access to your 
medical care or give up any legal rights or benefits. 
 
This document has important information to help you make your choice. Take time to read it.  
Talk to your doctor, family, or friends about the risks and benefits of taking part in the study.  
It’s important that you have as much information as you need and that all your questions are 
answered.  See the “Where can I get more information?” section for resources for more clinical 
trials and general cancer information. 
 
 


 
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Why is this study being done? 
 
This study is being done to answer the following question:  
 
Can we lower the chance of your lung cancer growing or spreading by using a drug that targets a 
biomarker present in your tumor? 
 
We are doing this study because we want to find out if this approach is better or worse than the 
usual approach for your lung cancer.  The usual approach is defined as care most people get for 
their lung cancer. 
 
What is the usual approach to my lung cancer? 
 
The usual approach for patients who are not in a study is treatment with chemotherapy or 
immunotherapy drugs.  If you have already received chemotherapy, other chemotherapy drugs or 
immunotherapy may be an option.  If you have already received immunotherapy, chemotherapy 
may be an option.  In addition, immunotherapy has been Food and Drug Administration (FDA) 
approved for patients with previously untreated non-small cell lung cancer whose tumors have 
high expression of a marker called PD-L1, as well as for patients who previously received 
chemotherapy and then had progression of their cancer.  
  
What are my choices if I decide not to take part in this study? 
 
• You may choose to have the usual approach described above. 
• You may choose to take part in a different research study, if one is available. 
• You may choose not to be treated for cancer. 
• You may choose to only get comfort care to help relieve your symptoms and not get 
treated for your cancer.   
 
What will happen if I decide to take part in this study? 
 
If you decide to take part in this study, you will get the study drug (rucaparib), until your disease 
gets worse or the side effects become too severe.  
 
After you finish your study treatment, your doctor will continue to follow your condition for up 
to three years from the time you went on study and watch you for side effects. If your disease has 
not gotten worse, follow up visits will occur every 3 months for the first year, then every 6 
months up to 3 years from the time you go on study. If your disease has gotten worse, follow up 
visits will occur every 6 months for 2 years, then at the end of the 3 years from the time you go 
on study. At the follow up visits you will have a physical exam, blood tests, and scans.  Your 
doctor may give you other tests or procedures if they think they are needed for the regular care of 
your disease.  
 


 
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Should your disease worsen, you have the option to participate in a different sub-study. As 
before, the new sub-study that you will be offered will depend on a combination of the results of 
the previous testing done on your tumor sample and the sub-studies available. If the tests show 
that your tumor has more than one biomarker that qualifies you for a different sub-study, you 
will be assigned to one of these sub-studies randomly (by chance). A sub-study may be available 
if your tumor does not have any additional biomarkers being tested or you were not eligible to 
participate in other sub-studies. 
 
What are the risks and benefits of taking part in this study? 
 
There are both risks and benefits to taking part in this study.  It is important for you to think 
carefully about these as you make your decision.     
 
Risks 
 
We want to make sure you know about a few key risks right now.  We give you more 
information in the “What risks can I expect from taking part in this study?” section. 
 
If you choose to take part in this study, there is a risk that the study approach may not be as good 
as the usual approach for your cancer at shrinking or stabilizing your cancer.   
 
There is also a risk that you could have side effects from the study drug. These side effects may 
be worse and may be different than you would get with the usual approach for your cancer.   
 
Some of the most common side effects that the study doctors know about are: 
• Nausea and vomiting 
• Diarrhea and constipation 
• Tiredness 
• Decreased appetite 
• Changes in taste 
• Sensitivity to sunlight 
 
Some of the rare side effects that the study doctors know about are: 
• Damage to bone marrow (irreversible) which may cause infection, bleeding, and may 
require transfusions 
• Cancer of the blood and bone marrow 
 
There may be some risks that the study doctors do not yet know about.   
 
Benefits 
 
There is evidence that rucaparib could shrink your type of cancer or prevent it from returning. It 
is unlikely that it will work in everyone with your cancer or help you live longer. This study will 
help the study doctors learn things that may help other people in the future. 
 


 
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If I decide to take part in this study, can I stop later? 
 
Yes, you can decide to stop taking part in the study at any time.  
 
If you decide to stop, let your study doctor know as soon as possible.  It’s important that you stop 
safely.  This may mean slowly stopping the study drug so that there is not a sudden, unsafe 
change, risk to your health. If you stop, you can decide if you want to keep letting the study 
doctor know how you are doing. 
 
Your study doctor will tell you about new information or changes in the study that may affect 
your health or your willingness to continue in the study. 
 
Are there other reasons why I might stop being in the study? 
 
Yes.  The study doctor may take you off the study if: 
 
• Your health changes and the study is no longer in your best interest. 
• New information becomes available and the study is no longer in your best interest. 
• You do not follow the study rules. 
• For women: You become pregnant while on the study. 
• The study is stopped by the National Cancer Institute (NCI), Institutional Review Board 
(IRB), Food and Drug Administration (FDA), or study sponsor (SWOG).  The study 
sponsor is the organization who oversees the study.   
 
It is important that you understand the information in the informed consent before making 
your decision. Please read, or have someone read to you, the rest of this document. If there is 
anything you don’t understand, be sure to ask your study doctor or nurse. 
 
End of Overview and Key Information  
 
What is the purpose of this study? 
 
There are several investigational treatments that are being tested in various sub-studies as part of 
this study. You will have already received the information on your biomarker testing. You have 
been assigned to this treatment study because your tumor sample is LOH-positive (Loss of 
Heterozygosity, which is a genomic variation in the make-up of your cells) or BRCA-positive (a 
mutation in either the BRCA1 or BRCA2 genes, which are tumor suppressor genes). LOH and 
BRCA are changes in genes that may make your cancer respond to a poly (ADP) ribose 
polymerase (PARP) inhibitor. A PARP inhibitor is a drug that blocks the PARP enzyme in cells. 
The PARP enzyme helps cancer cells to be able to repair, and inhibiting this enzyme can cause 
cancer cells to die. For this sub-study, you will be assigned to treatment with an investigational 
drug called rucaparib, a PARP inhibitor.  
 
 


 
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The purpose of this study is to test the good and bad effects of the study drug, rucaparib.  
Rucaparib is a drug that works by slowing or stopping the growth of cancer cells, but it could 
also cause side effects, which are described in the risks section below.  The study doctors hope to 
learn if the study drug will shrink the cancer by at least one quarter compared to its present size.   
Another purpose of this study is for the study doctors to learn if a biomarker test for LOH or 
BRCA 1 or BRCA 2 genes is helpful in assigning treatment.  
 
Rucaparib is not approved by the FDA for use in advanced lung cancer.  There will be up to 88 
people taking part in this study. 
 
What are the study groups? 
 
This study has 2 study groups. Both groups will receive rucaparib.  
 
Rucaparib will be taken twice daily at about the same time every day. The tablets will be 
swallowed whole without crushing. You will take the tablets with at least 8 oz. of water with or 
without food. You will not make up skipped doses. 
 
• Group 1 – Receive rucaparib for your squamous cell lung cancer 
 
If you are in this group, you will get the study drug called rucaparib for your squamous 
cell lung cancer. Rucaparib will be given by mouth twice a day about the same time 
every day as close to 12 hours apart as possible. It is important to swallow whole and not 
to chew the tablets. You will receive rucaparib until your disease gets worse or the side 
effects become too severe. Each cycle lasts 21 days.  
 
You also will keep a pill diary.  This helps you keep track of when you take your pills.  
The study doctor will show you how to use this diary.  Each time you visit the clinic, you 
must bring the pill diary, any remaining pills, and the pill bottle. 
 
There will be up to 44 people in this group. 
 
• Group 2 – Receive rucaparib for your non-squamous cell lung cancer 
 
If you are in this group, you will get the study drug called rucaparib for your non-
squamous cell lung cancer.  Rucaparib will be given by mouth twice a day about the 
same time every day as close to 12 hours apart as possible. It is important to swallow 
whole and not to chew the tablets. You will receive rucaparib until your disease gets 
worse or the side effects become too severe. Each cycle lasts 21 days.  
 
You also will keep a pill diary.  This helps you keep track of when you take your pills.  
The study doctor will show you how to use this diary.  Each time you visit the clinic, you 
must bring the pill diary, any remaining pills, and the pill bottle. 
 


 
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There will be up to 44 people in this group. 
 
You will be put into Group 1 if you have squamous cell lung cancer. You will be put into Group 
2 if you have non-squamous cell lung cancer.  
 
Another way to find out what will happen to you during this study is to read the chart below. 
Start reading at the left side and read across to the right, following the lines and arrows.  
 
 
 
 
What exams, tests, and procedures are involved in this study? 
 
Before you begin the study, there are some extra tests that you will need to have if you take part 
in this study: 
 
• Blood Test (circulating tumor DNA) 
You will be required to have about 2.5 tablespoons of your blood collected for the 
circulating tumor DNA testing.  An attempt will be made to do this blood draw at the 
same time as other blood draws. There is a chance that you will have another stick to 
obtain the blood. This blood will be tested for DNA not normally found in cells but that is 
present in your blood because it has been released from the tumors in your body.  The 
information collected will help the study doctors learn about tumor abnormalities that 
may play a role in tumor evolution. The results of this blood test are not part of normal 
clinical decision making. You and your doctor will not receive the results of this blood 
test. 
 
 
What risks can I expect from taking part in this study? 
 
General Risks 
 
If you choose to take part in this study, there is a risk that the study approach may not be as good 
as the usual approach for your cancer at shrinking or stabilizing your cancer.   
 
 
Group 2 
Receive rucaparib for 
your non-squamous cell 
lung cancer 
You agree to take 
part in the study 
and sign this 
consent form. 
Group 1 
Receive rucaparib for 
your squamous cell lung 
cancer 


 
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You also may have the following discomforts: 
 
• Spend more time in the hospital or doctor’s office. 
• Be asked sensitive or private questions about things you normally do not discuss. 
• May not be able to take part in future studies.  
 
The drug used in this study could be very harmful to an unborn or newborn baby.  There may be 
some risks that doctors do not yet know about.  It is very important that you check with your 
study doctor about what types of birth control or pregnancy prevention to use during the study 
and for 6 months after you have completed the study. 
 
Side Effect Risks 
 
The drug used in this study may affect how different parts of your body work such as your liver, 
kidneys, heart, and blood.  The study doctor will test your blood and let you know if changes 
occur that may affect your health. 
 
There is also a risk that you could have other side effects from the study drug. 
 
Here are important things to know about side effects: 
 
1. The study doctors do not know who will or will not have side effects. 
2. Some side effects may go away soon, some may last a long time, and some may never go 
away. 
3. Some side effects may make it hard for you to have children. 
4. Some side effects may be mild.  Other side effects may be very serious and even result in 
death. 
 
You can ask your study doctor questions about side effects at any time.  Here are important ways 
to make side effects less of a problem: 
 
• If you notice or feel anything different, tell your study doctor.  He or she can check to see 
if it is a side effect. 
• Your study doctor will work with you to treat your side effects. 
• Your study doctor may adjust the study drugs to try to reduce side effects. 
 
Drug Risks 
 
The tables below show the most common and most serious side effects doctors know about.  
Keep in mind that there might be other side effects doctors do not yet know about.  If important 
new side effects are found, the study doctor will discuss these with you. 
 
Possible side effects of rucaparib are listed in the tables below.   
 
 


 
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Possible Side Effects of Rucaparib  
(Table Version Date: November 2, 2020) 
 
COMMON, SOME MAY BE SERIOUS   
In 100 people receiving rucaparib, more than 20 and up to 100 may have: 
 
• Anemia which may cause tiredness, or may require blood transfusion 
• Bruising and bleeding 
• Pain in belly 
• Constipation 
• Diarrhea 
• Nausea  
• Vomiting 
• Tiredness 
• Decreased appetite  
• Changes in taste 
 
OCCASIONAL, SOME MAY BE SERIOUS   
In 100 people receiving rucaparib, from 4 to 20 may have:  
• Bloating 
• Heartburn 
• Dry mouth 
• Painful swelling and sores inside the mouth 
• Swelling of mucous linings in the body 
• Swelling of arms, legs 
• Fever 
• Infection especially when white blood cell count is low 
• Cold symptoms such as stuffy nose, sneezing, sore throat 
• Infection which may cause painful and frequent urination 
• Dehydration 
• Pain in joints 
• Pain in back 
• Pain in muscles, bone, ligaments, nerves 
• Pain in arms, legs 
• Dizziness 
• Headache 
• Worry 
• Depression 
• Difficulty sleeping 
• Cough 
• Shortness of breath 


 
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• Hair loss 
• Dry skin 
• Redness of the skin 
• Increased risk of sunburn 
• Itching 
• Rash 
• Hot flash 
• High blood pressure which may cause headaches, dizziness, blurred vision 
 
RARE, AND SERIOUS 
In 100 people receiving rucaparib, 3 or fewer may have: 
• Damage to bone marrow (irreversible) which may cause infection, bleeding, and 
may require transfusions 
• Cancer of the blood and bone marrow such as acute myeloid leukemia (AML) or 
myelodysplastic syndrome (MDS) 
• Damage to the lungs which may cause shortness of breath 
 
 
Additional Drug Risks 
 
Photosensitivity Reaction 
 
It is possible that rucaparib may make your skin and eyes more sensitive to sunlight. You should 
take all of the usual sun protection precautions when going outside. It is advised that you avoid 
excessive sun exposure, wear protective clothing (including wearing a hat and sunglasses), and 
use sunscreens regularly (sun protection factor 50 or greater).  
 
Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) 
 
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been reported in a 
very small number of patients treated with rucaparib.  MDS is a pre-cancerous condition where 
the bone marrow is not as good at producing blood cells (red and/or white blood cells and/or 
platelets) as it was before.  People with MDS need transfusions (red blood cells and/or platelets) 
and/or other treatments.  In some cases, MDS will progress to AML, which is a cancer of the 
bone marrow where more abnormal and immature white blood cells (also called blasts) are made 
than normal white blood cells.  People with AML need treatment with chemotherapy and/or a 
transplant.  Patients may develop AML without first being diagnosed with MDS. 
 
Cases of MDS and AML have also been reported with PARP inhibitors similar to rucaparib.  At 
this time, it is not known whether rucaparib or other PARP inhibitors cause MDS or AML, or if 
these developed as a result of previous chemotherapy these patients received.  Your study doctor 


 
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will closely monitor your blood cell levels during treatment.  If your study doctor has any 
concerns about your blood counts you may be asked to have a biopsy of your bone marrow. 
Drug Interactions 
 
Over the counter, herbal medicines and other prescribed drugs will be reviewed by the study 
team for potential drug interactions.  Your doctor or a member of the study team will tell you if 
you need to stop, modify or change any of these medicines or drugs before you start taking 
rucaparib. If you are taking metformin (for diabetes), drugs that inhibit a substance known as 
BCRP (such as the statin rosuvastatin, often called Crestor), or warfarin (such as Coumadin, for 
blood clots) while you are taking rucaparib, your doctor will monitor you closely during 
treatment. Throughout your treatment, you should inform your doctor about any medication 
changes.  
Rarely, there are problems getting enough supplies of the study drug.  If that happens, your 
doctor will talk with you about your options. 
 
What are my responsibilities in this study? 
 
If you choose to take part in this study you will need to: 
 
• Keep your study appointments. 
• Tell your doctor about: 
o all medications and supplements you are taking 
o any side effects  
o any doctors’ visits or hospital stays outside of this study  
o and if you have been or are currently in another research study. 
 
For women: Do not get pregnant or breastfeed while taking part in this study. You must 
continue to use your approved method of birth control during the study and for 6 months after 
last dose.   
For men: Do not father a baby while taking part in this study. You must continue to use your 
approved method of birth control during the study and for 3 months after last dose. Do not 
donate sperm while taking part in this study and for 3 months after your last dose of study 
treatment. 
For all: Tell your study doctor right away if you think that you or your partner have become 
pregnant during the study or within 6 months after your last dose of study treatment. 
 
What are the costs of taking part in this study? 
 
You and/or your insurance plan will need to pay for the standard of care costs of medical care 
you get as part of the study, just as you would if you were getting the usual care for your cancer.  
This includes: 
 


 
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• the costs of tests, exams, procedures, and drugs that you get during the study to monitor 
your safety, and prevent and treat side effects.   
• the costs of getting the study agent (rucaparib) ready and giving it to you. 
• your insurance co-pays and deductibles. 
 
Talk to your insurance provider and make sure that you understand what your insurance pays for 
and what it doesn’t pay for if you take part in this clinical trial.  Also, find out if you need 
approval from your plan before you can take part in the study.  
 
Ask your doctor or nurse for help finding the right person to talk to if you are unsure which costs 
will be billed to you or your insurance provider.  
 
You and/or your insurance provider will not have to pay for exams, tests, and procedures done 
for research purposes only or that are covered by the study. This includes: 
 
• The collection or testing of the circulating tumor DNA at the beginning of the study. 
 
You or your insurance provider will not have to pay for the rucaparib while you take part in this 
study.  
 
Taking part in this study may mean that you need to make more visits to the clinic or hospital 
than if you were getting the usual approach to treat your cancer.  You may: 
 
• Have more travel costs. 
• Need to take more time off work. 
• Have other additional personal costs. 
 
You will not be paid for taking part in this study.  The research may lead to new tests, drugs, or 
other products for sale.  If it does, you will not get any payment.   
 
What happens if I am injured because I took part in this study? 
 
If you are injured as a result of taking part in this study and need medical treatment, please talk 
with your study doctor right away about your treatment options.  The study sponsors will not pay 
for medical treatment for injury.  Your insurance company may not be willing to pay for a study-
related injury.  Ask them if they will pay.  If you do not have insurance, then you would need to 
pay for these medical costs. 
 
If you feel this injury was caused by medical error on the part of the study doctors or others 
involved in the study, you have the legal right to seek payment, even though you are in a study.  
Agreeing to take part in this study does not mean you give up these rights. 
 
Who will see my medical information? 
 


 
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Your privacy is very important to us.  The study doctors will make every effort to protect it.  The 
study doctors have a privacy permit to help protect your records if there is a court case. 
However, some of your medical information may be given out if required by law.  If this should 
happen, the study doctors will do their best to make sure that any information that goes out to 
others will not identify who you are.  
 
Some of your health information, such as your response to cancer treatment, results of study 
tests, and medicines you took, will be kept by the study sponsor in a central research database.  
However, your name and contact information will not be put in the database.  If information 
from this study is published or presented at scientific meetings, your name and other personal 
information will not be used.  
 
There are organizations that may look at your study records.  Your health information in the 
research database also may be shared with these organizations.  They must keep your 
information private, unless required by law to give it to another group.   
 
Some of these organizations are: 
 
• The study sponsor, SWOG and any company supporting the study now or in the future.  
• The Institutional Review Board, (IRB), which is a group of people who review the 
research with the goal of protecting the people who take part in the study. 
• The Food and Drug Administration, (FDA), and the groups it works with to review 
research.   
• The National Cancer Institute, (NCI), and the groups it works with to review research. 
• The NCI’s National Clinical Trials Network and the groups it works with to conduct 
research. 
Transmission of Imaging and Data (TRIAD) and Imaging and Radiation Oncology Core 
(IROC) – Your medical images with clinical study data (e.g., the treatment Group you re 
assigned to, etc.) will be transferred using a computer program called TRIAD or IROC, a 
central imaging laboratory sponsored by the NCI and located at Ohio State University in 
Columbus, Ohio.  Your medical images will be reviewed by physicians at this 
organization as part of the study analysis for this trial. 
 
Your study records also will be stored for future use.  However, your name and other personal 
information will not be used.  Some types of future research may include looking at your records 
and those of other patients to see who had side effects across many studies or comparing new 
study data with older study data.  However, we don’t know what research may be done in the 
future using your information.  This means that: 
 
• You will not be asked if you agree to take part in the specific future research studies 
using your health information.   
• You and your study doctor will not be told when or what type of research will be done. 
• You will not get reports or other information about any research that is done using your 
information.  
 


 
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There are laws that protect your genetic information.  However, there is a risk that someone 
could get access to your genetic information and identify you by name.  In some cases, 
employers could use your genetic information to decide whether to hire or fire you.  The study 
doctors believe the risk of this happening is very small.  However, the risk may increase in the 
future as people find new ways of tracing information.  For more information about the laws that 
protect you, ask your study doctor. 
 
Where can I get more information?   
 
You may visit the NCI web site at http://cancer.gov/ for more information about studies or 
general information about cancer.  You may also call the NCI Cancer Information Service to get 
the same information at: 1-800-4-CANCER (1-800-422-6237). 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
 
You can talk to the study doctor about any questions or concerns you have about this study or to 
report side effects or injuries.  Contact the study doctor __________________ (insert name of 
study doctor[s]) at __________________ (insert telephone number). 
 
For questions about your rights while in this study, call the __________________ (insert name 
of organization or center) Institutional Review Board at __________________ (insert telephone 
number).  
 
Optional studies that you can choose to take part in 
 
This part of the consent form is about optional studies that you can choose to take part in.  They 
are separate from the main study described above.  These optional studies will not benefit your 
health.  The researchers leading these optional studies hope the results will help other people 
with cancer in the future. The results will not be added to your medical records and you or your 
study doctor will not know the results. 
 
Taking part in these optional studies is your choice.  You can still take part in the main study 
even if you say “no” to any or all of these studies. There is no penalty for saying “no.” You and 
your insurance company will not be billed for these optional studies.  If you sign up for, but 
cannot complete any of these studies for any reason, you can still take part in the main study. 
 
Circle your choice of “yes” or “no” for each of the following studies. 
 
Future contact 
I agree to allow my study doctor, or someone approved by my study doctor, to contact me 
regarding future research involving my participation in this study.  


 
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Yes 
No 
 
Optional sample collections for known laboratory studies and/or storage for possible 
future studies 
 
Researchers are trying to learn more about cancer and other health problems using blood samples 
from people who take part in clinical trials.  By studying these samples, researchers hope to find 
new ways to prevent, detect, treat, or cure diseases. 
 
Some of these studies may be about how genes affect health and disease.  Other studies may look 
at how genes affect a person’s response to treatment.  Genes carry information about traits that 
are found in you and your family.  Examples of traits are the color of your eyes, having curly or 
straight hair, and certain health conditions that are passed down in families.  Some of the studies 
may lead to new products, such as drugs or tests for diseases. 
 
Unknown future studies 
 
If you choose to take part in this optional study, your blood samples will be collected and stored.  
Storing samples for future studies is called “biobanking.”  The biobank is being run by SWOG 
and is supported by the NCI.  Also, any health-related information, such as your response to 
cancer treatment, results of study tests, and medicines you took, will be stored for future use.   
 
We don’t know what research may be done in the future using your blood and tissue samples.   
 
This means that: 
 
• You will not be asked if you agree to take part in the future research studies.   
• You and your study doctor will not be told when or what type of research will be done. 
• Future research studies may include sequencing of all or part of your DNA called 
genomic sequencing.  All your genetic information makes up your genome.  Genomic 
sequencing is a test that records all or part of the pieces of DNA that are in your genes, 
piece by piece.  This is usually done to look for changes in your genome that may cause 
health problems.   
• You will not get reports or other information about any research that is done using your 
samples.  
 
What is involved in this optional sample collection? 
 
If you agree to take part, here is what will happen next: 
 
1. About 2 tablespoons of blood will be collected from a vein in your arm (at the same time 
as other study blood tests) on Weeks 4, 7, 10, and again if your cancer gets worse.  


 
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2. Your samples will be stored in the biobank.  There is no limit on the length of time we 
will keep your samples and research information.  The samples will be kept until they are 
used for research or destroyed. 
3. Researchers can only get samples from the biobank after their research has been 
approved by experts.  Researchers will not be given your name or contact information.   
4. Some of your genetic and health information may be placed in central databases for 
researchers to use.  The databases will not include your name or contact information.   
 
What are the risks in this optional sample collection? 
 
1. The most common risks related to drawing blood from your arm are brief pain and maybe 
a bruise.   
2. Your medical and genetic information is unique to you.  There is a risk that someone 
outside of the research study could get access to your study records or trace information 
in a database back to you.  They could use that information in a way that could harm you.  
Researchers believe the chance that someone could access and misuse your information is 
very small.  However, the risk may increase in the future as people find new ways of 
tracing information.  
3. In some cases, this information could be used to make it harder for you to get or keep a 
job and get or keep health insurance.  There are laws against the misuse of genetic 
information, but they may not give full protection. For more information about the laws 
that protect you, ask your study doctor or visit:  https://www.genome.gov/10002328/  
 
How will information about me be kept private? 
 
Your privacy is very important to the study researchers and biobank.  They will make every 
effort to protect it.  Here are just a few of the steps they will take: 
 
1. They will remove identifiers, such as your initials, from your sample and information.   
They will replace them with a code number.  There will be a master list linking the code 
numbers to names, but they will keep it separate from the samples and information. 
2. Researchers who study your sample and information will not know who you are.   They 
also must agree that they will not try to find out who you are. 
3. Your personal information will not be given to anyone unless it is required by law.  
4. If research results are published, your name and other personal information will not be 
used. 
 
 
 


 
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What are the benefits to taking part in this optional sample collection? 
 
You will not benefit from taking part.  
 
The researchers, using the samples from you and others, might make discoveries that could help 
people in the future. 
 
Are there any costs or payments to this optional sample collection? 
 
There are no costs to you or your insurance.  You will not be paid for taking part in this study.  
The research may lead to new tests, drugs, or other products for sale.  If it does, you will not get 
any payment. 
 
What if I change my mind about this optional sample collection? 
 
If you decide you no longer want your samples to be used, you can call the study doctor, 
______________________ (insert name of study doctor for main trial) at __________________ 
(insert telephone number of study doctor for main trial), who will let the biobank know.  Then, 
any sample that remains in the biobank will be destroyed or returned to your study doctor.  This 
will not apply to any samples or related health information that have already been given to or 
used by researchers. 
 
What if I have questions about this optional sample collection? 
 
If you have questions about the use of your samples for research, contact the study doctor, 
______________________ (insert name of study doctor for main trial) at __________________ 
(insert telephone number of study doctor for main trial). 
 
Please circle your answer below to show if you would or would not like to take part in each 
optional study: 
 
Samples for unknown future studies: 
 
 
1. 
My samples and related information may be kept in a Biobank for use in future 
health research. 
 
YES 
 
NO 
 
This is the end of the section about optional studies. 
 
 
 


 
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My signature agreeing to take part in the study 
 
I have read this consent form or had it read to me.  I have discussed it with the study doctor and 
my questions have been answered.  I will be given a signed and dated copy of this form.  I agree 
to take part in the main study.  I also agree to take part in any additional studies where I circled 
“yes”. 
 
Participant’s signature (or legally authorized representative)  
_____________________________________________________________________________ 
 
Date of signature   ______________________________________________________________  
 
 
Signature of person(s) conducting the informed consent discussion 
 
_____________________________________________________________________________  
 
Date of signature   ______________________________________________________________