A Study To Evaluate Rucaparib In Participants With Solid Tumors And With Deleterious Mutations In HRR Genes

Study Overview

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

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.

N/A

Solid Tumor

DRUG: Rucaparib

CO-338-100

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-11-19	Results First Submitted 2023-05-31	Last Update Submitted that met QC Criteria 2023-09-29
First Submitted that Met QC Criteria 2019-11-19	Results First Submitted that Met QC Criteria 2023-09-29	Last Update Posted (ACTUAL) 2023-10-02
First Posted (ACTUAL) 2019-11-21	Results First Posted 2023-10-02	Last Verified 2023-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Rucaparib 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 BARD	DRUG: Rucaparib Oral rucaparib will be administered twice daily. The starting dose will be 600 mg daily (BID).

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Rucaparib

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 BARD

DRUG: Rucaparib

Oral rucaparib will be administered twice daily. The starting dose will be 600 mg daily (BID).

Primary Outcome Measures	Measure Description	Time Frame
Best Overall Response Rate by Investigator	Best overall response rate as assessed by the investigator by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer).	From first dose of study drug until disease progression (up to approximately 2 years)

Secondary Outcome Measures	Measure Description	Time Frame
Overall Response Rate by Independent Radiology Review	Best overall response rate by independent radiology review by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer).	From first dose of study drug until disease progression (up to approximately 2 years)
Duration of Response	Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression.	From first dose of study drug until disease progression (up to approximately 2 years)
Disease Control Rate	Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks.	From first dose of study drug until disease progression (up to approximately 2 years)
Progression-free Survival	Measure of clinical benefit, defined as the duration from study enrollment to objective tumor progression. Progression was defined using RECIST v1.1, as a 20% increase in the sum of diameters of target lesions (and an absolute increase of at least 5 mm), or unequivocal progression of existing non-target lesions, or the appearance of new lesions. For mCRPC disease, the PCWG3 confirmed bone disease progression criteria (2+2) were also incorporated.	From first dose of study drug until disease progression (up to approximately 2 years)
Overall Survival	Measure of clinical benefit, defined as the duration from study enrollment to death.	From first dose of study drug until disease progression (up to approximately 2 years)
Number of Participants Experiencing Treatment-emergent Adverse Events		From first dose of study drug until disease progression (up to approximately 2 years)
Steady State Minimum Concentration [Cmin]	Rucaparib pharmacokinetics	From first dose of study drug until disease progression (up to approximately 2 years)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Kim Reiss-Binder, MD, University of Pennsylvania

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Anbil S, Seewald NJ, Chiorean EG, Hussein M, Kasi PM, Laux DE, Schwartz GK, Shapiro GI, Lin KK, Craib M, Maloney L, McLachlan K, Tukachinsky H, Schrock AB, Wang S, Sokol ES, Decker B, Nathanson KL, Domchek SM, Reiss KA. LODESTAR: A Single-Arm Phase II Study of Rucaparib in Solid Tumors With Pathogenic Germline or Somatic Variants in Homologous Recombination Repair Genes. JCO Precis Oncol. 2025 Jul;9:e2500090. doi: 10.1200/PO-25-00090. Epub 2025 Jul 9.

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