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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)

NCT03845296

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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)

Clinical Trial IDs

  • ORG STUDY ID: S1900A
  • SECONDARY ID: NCI-2018-02129
  • SECONDARY ID: S1900A
  • SECONDARY ID: S1900A
  • SECONDARY ID: U10CA180888
  • NCT ID: 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

Interventions

DrugSynonymsArms
Rucaparib6H-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-oneTreatment (rucaparib)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (rucaparib)ExperimentalPatients receive rucaparib PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Rucaparib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

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