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Rucaparib in Treating Patients With Genomic LOH High and/or Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)

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ClinicalTrials.gov Identifier: NCT03845296
Recruitment Status : Recruiting
First Posted : February 19, 2019
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE February 15, 2019
First Posted Date  ICMJE February 19, 2019
Last Update Posted Date September 9, 2019
Actual Study Start Date  ICMJE January 28, 2019
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2019)
  • Investigator assessed progression free survival (PFS) [ Time Frame: From date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years ]
    Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times.
  • Duration of response (DoR) [ Time Frame: From date of first documentation of response (complete response [CR] or partial response [PR]) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause, assessed up to 3 years ]
    Response will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Response rates and associated confidence intervals will be calculated. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times. Response rates can be estimated within 16% with 95% confidence.
  • Overall survival [ Time Frame: From date of sub-study registration to date of death due to any cause, assessed up to 3 years ]
    Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times.
  • Time to death [ Time Frame: From date of sub-study registration to date of death due to any cause, assessed up to 3 years ]
  • Incidence of adverse events [ Time Frame: Up to 3 years ]
    Toxicity will be evaluated among all patients enrolled on the study (combining the squamous and non-squamous cohorts). Toxicity can be estimated to within 11% with 95% confidence.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03845296 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rucaparib in Treating Patients With Genomic LOH High and/or Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: Rucaparib
Given PO
Other Names:
  • 6H-Pyrrolo(4,3,2-ef)(2)benzazepin-6-one, 8-Fluoro-1,3,4,5-tetrahydro-2-(4-((methylamino)methyl)phenyl)-
  • 8-Fluoro-2-(4-((methylamino)methyl)phenyl)-1,3,4,5-tetrahydro-6H-azepino(5,4,3-cd)indol-6-one
Study Arms  ICMJE Experimental: Treatment (rucaparib)
Patients receive rucaparib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: Drug: Rucaparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 15, 2019)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2021
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must meet all SCREENING/PRE-SCREENING and SUB-STUDY REGISTRATION COMMON ELIGIBILITY CRITERIA as specified in S1400: Phase II/III Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map)
  • Patients must be assigned to S1900A. S1900A biomarker eligibility defined as LOH high and/or deleterious BRCA1/2 mutation is as follows using the Foundation Medicine Inc (FMI) tissue- assay:

    • LOH; alteration type: loss of heterozygosity (LOH); eligible alteration: Genomic LOH >= 21%
    • BRCA; alteration type: homologous recombination deficiency (HRD); eligible alteration: Deleterious mutations in BRCA1 or BRCA2
  • 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.
  • Patients must be able to take oral medications.
  • Patients must not have a >= Grade 3 hypercholesterolaemia (defined by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5) within 28 days prior to sub-study registration.
  • 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.
  • Patients must not have documented evidence of acute hepatitis or have an active or uncontrolled infection.
  • Patients with a known history of human immunodeficiency virus (HIV) seropositivity:

    • Must have undetectable viral load using standard HIV assays in clinical practice.
    • Must have CD4 count >= 400/mcL.
    • Must not require prophylaxis for any opportunistic infections (i.e., fungal, mycobacterium avium complex [mAC], or pneumocystis pneumonia [PCP] prophylaxis).
    • Must not be newly diagnosed within 12 months prior to sub-study registration.
  • Patients must have progressed (in the opinion of the treating physician) following the most recent line of therapy.
  • 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.
  • Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment 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.
  • Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. 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. CT and MRI scans must be submitted for central review via TRIAD.
  • Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (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.
  • 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.
  • Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to sub-study registration)
  • Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study registration)
  • Hemoglobin >= 9 g/dL (obtained within 28 days prior to sub-study registration)
  • Serum bilirubin =< Institutional Upper Limit of Normal (IULN). For patients with liver metastases, bilirubin must be =< 5 x IULN (within 28 days prior to sub-study registration)
  • Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN (if both ALT and AST are done, both must be < 2 IULN). For patients with liver metastases, either ALT or AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN) (within 28 days prior to sub-study registration)
  • Patients must have a serum creatinine =< the IULN OR calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to sub-study registration.
  • Patients must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration.
  • 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.
  • Pre-study history and physical exam must be obtained within 28 days prior to sub-study registration.
  • 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.
  • Patients must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method during the study and 6 months after study completion. 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 6 months after study completion
  • Patients must agree to have blood specimens submitted for circulating tumor DNA (ctDNA).
  • Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03845296
Other Study ID Numbers  ICMJE S1900A
NCI-2018-02129 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1900A ( Other Identifier: SWOG )
S1900A ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Jonathan W Riess Southwest Oncology Group
PRS Account Southwest Oncology Group
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP