A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes
Condition: Solid Tumor
MeSH terms: Neoplasms
Intervention: Rucaparib
Intervention description: Oral rucaparib will be administered twice daily. The starting dose will be 600 mg daily (BID).
Intervention MeSH terms: Rucaparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 83.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: rucaparib; PARPi; rare tumor; solid tumor; CO-338; ovarian cancer; prostate cancer; pancreatic cancer; breast cancer; lung cancer; colon cancer; gastric cancer; bladder cancer; colorectal cancer; PARP inhibitor; homologous recombination; DNA repair; LODESTAR; germline; somatic; BRCA1; BRCA2; PALB2; RAD51C; RAD51D; BARD1; BRIP1; FANCA; RAD51; RAD51B; sarcoma; HRR; HRD; platinum sensitive; platinum resistant; primary peritoneal cancer; fallopian tube cancer; tumor agnostic; basket study; basket trial; metastatic; locally advanced; esophageal cancer; leiomyosarcoma; ampullary carcinoma; carcinosarcoma; endometrial cancer; cervical cancer

Summary:

      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.
    

Eligibility 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