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)
18 Years and older, Male and Female
S1900A (primary)
NCI-2018-02129
S1900A
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 (recurrent). PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as rucaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing.
Objectives
PRIMARY OBJECTIVE:
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:
Ia. Cohort 1: Patients with squamous cell histology.
Ib. Cohort 2: Patients with non-squamous histology (adenocarcinoma, large cell, or non-small cell lung cancer [NSCLC] not otherwise specified [NOS], or mixed histology with any non-squamous component).
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).
TRANSLATIONAL 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. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI) throughout the study.
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.
Eligibility
- 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 be able to take oral medications.
- Patients with known >= grade 3 hypercholesterolaemia 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. >= 3 hypercholesterolemia (“cholesterol high”) is defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 as blood cholesterol measurement > 400 mg/dL.
- 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 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.
- 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.
- 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 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.
- 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.
- As a part of the OPEN registration process 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.
- Patients with impaired decision-making capacity are eligible as long as their neurological or psychologic condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator).
Treatment Sites in Georgia
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