A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes (LODESTAR)

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Status and phase: Terminated; Phase 2

Conditions: Solid Tumor

Treatments: Drug: Rucaparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04171700

CO-338-100

Details and patient eligibility

About

A Phase 2, open-label, single-arm trial to evaluate the response of rucaparib in participants with various solid tumors and with deleterious mutations in Homologous Recombination Repair (HRR) genes.

Enrollment: 83 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Unresectable, locally advanced or metastatic solid tumor and relapsed/progressive disease
• Measurable disease per RECIST v1.1 or modified RECIST v1.1 and PCWG3 (for prostate cancer)
• Have a deleterious mutation (germline or somatic) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B. Note: Breast cancer patients that are HER2 negative and have germline BRCA1 or BRCA2 mutations AND patients with epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer or metastatic castration-resistant prostate cancer with BRCA1 or BRCA2 mutations are ineligible for this trial.
• At least one prior line of therapy extending overall survival or standard of care therapy for advanced disease. Note: Some tumor types have specific inclusion/exclusion criteria for previous treatments.
• ECOG 0 or 1
• Tumor tissue available for genomic analysis, or must be willing to have a biopsy if no archival tumor tissue available
• Adequate organ function
• Life expectancy of 4 months

Key Exclusion Criteria:

• Active central nervous system brain metastases, leptomeningeal disease or primary tumor of CNS origin
• Active second malignancy (Exceptions: Successfully treated malignancy with no active disease for 1 year, surgically cured and/or low-risk tumors, or patients receiving ongoing anticancer hormonal therapy for a previously treated cancer)
• Pre-existing gastrointestinal disorders/conditions interfering with ingestion/absorption of rucaparib
• Prior treatment with a PARP inhibitor
• More than 3 prior lines of chemotherapy in the locally advanced/metastatic setting
• History of myelodysplastic syndrome or acute myeloid leukemia

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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83 participants in 1 patient group

Rucaparib

Experimental group

Description:

Eligible participants will be enrolled in either Cohort A or Cohort B. Cohort A: Up to 200 participants with deleterious mutations in BRCA1, BRCA2, PALB2, RAD51C or RAD51D. Cohort B (Exploratory): Up to 20 participants with deleterious mutations in BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B.

Treatment:

Drug: Rucaparib