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)

Summary

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.