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.
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
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Given PO
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
Anchorage Associates in Radiation Medicine
Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States
Overall Response Rate
Percentage of participants with a complete or partial, confirmed or unconfirmed response. Complete Response (CR): Complete disappearance of all target and non-target lesions. 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. Partial Response (PR): Applies only to participants 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.
Time frame: From date of registration to a maximum of 3 years or death
Investigator-Assessed Progression-Free Survival (IA-PFS)
Time from date of registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause. Participants last known to be alive without report of progression are censored at date of last disease assessment. For participants 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) is used as the date of progression. Progression: One or more of: 20% increase in sum of diameters of target lesions over smallest sum observed and absolute increase of at least 0.5cm; Unequivocal progression of non-measurable disease in opinion of the treating physician; Appearance of any new lesion/site; Death due to disease w/o prior progression or symptomatic deterioration Symptomatic deterioration: Global deterioration of health status requiring treatment discontinuation w/o objective evidence of progression
Time frame: From date of registration to a maximum of 3 years or death
Overall Survival (OS)
Time from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact.
Time frame: From date of registration to a maximum of 3 years or death
Duration of Response (DoR)
Time from date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause among participants who achieve a response. Participants last known to be alive without report of progression are censored at date of last disease assessment. For participants with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan will be used as the date of progression.
Time frame: From date of registration to a maximum of 3 years or death
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 5.0 was used for routine toxicity reporting and serious adverse events (SAEs).
Time frame: Duration of treatment and follow up until death or 3 years post registration
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