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

• ClinicalTrials.gov Identifier: NCT04171700
• Recruitment Status: Terminated
• First Posted: November 21, 2019
• Results First Posted: October 2, 2023
• Last Update Posted: October 2, 2023
• Sponsor: pharmaand GmbH
• Information provided by (Responsible Party): pharmaand GmbH

Tracking Information

• First Submitted Date: November 19, 2019
• First Posted Date: November 21, 2019
• Results First Submitted Date: May 31, 2023
• Results First Posted Date: October 2, 2023
• Last Update Posted Date: October 2, 2023
• Actual Study Start Date: January 16, 2020
• Actual Primary Completion Date: June 8, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 11, 2023)

Best Overall Response Rate by Investigator [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]

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).

Original Primary Outcome Measures (submitted: November 19, 2019)

Best Overall Response Rate by Investigator [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]

Best overall response rate as assessed by the investigator by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in patients with advanced prostate cancer).

Current Secondary Outcome Measures (submitted: September 29, 2023)

• Overall Response Rate by Independent Radiology Review [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  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).
• Duration of Response [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression.
• Disease Control Rate [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks.
• Progression-free Survival [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  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.
• Overall Survival [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Measure of clinical benefit, defined as the duration from study enrollment to death.
• Number of Participants Experiencing Treatment-emergent Adverse Events [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
• Steady State Minimum Concentration [Cmin] [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Rucaparib pharmacokinetics

Original Secondary Outcome Measures (submitted: November 19, 2019)

• Overall Response Rate by Independent Radiology Review [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Best overall response rate by independent radiology review by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in patients with advanced prostate cancer)
• Duration of Response [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression.
• Disease Control Rate [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks.
• Progression-Free Survival [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Measure of clinical benefit, defined as the duration from study enrollment to objective tumor progression.
• Overall Survival [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Measure of clinical benefit, defined as the duration from study enrollment to death.
• Safety and Tolerability of rucaparib [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Incidence of AEs, clinical lab abnormalities, and dose modifications.
• Steady state minimum concentration [Cmin] [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
  Rucaparib PK

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes
• Official Title: A Phase 2 Multicenter, Open-label Study of Rucaparib as Treatment for Solid Tumors Associated With Deleterious Mutations in Homologous Recombination Repair Genes
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

Drug: Rucaparib

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

Other Names:

• Rubraca
• Rucaparib camsylate
• Rucaparib tablets
• CO-338
• PF 01367338
• AG 014447

Study Arms

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 BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B.

Intervention: Drug: Rucaparib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 2, 2022): 83
• Original Estimated Enrollment (submitted: November 19, 2019): 220
• Actual Study Completion Date: July 15, 2022
• Actual Primary Completion Date: June 8, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04171700
• Other Study ID Numbers: CO-338-100
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by Clovis Oncology.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: Data will be made available to qualified researchers after the primary, secondary, and/or exploratory outcomes of the study are reported or published and for 1 year thereafter.
• Access Criteria: Requests for de-identified datasets will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com.

• Current Responsible Party: pharmaand GmbH
• Original Responsible Party: Clovis Oncology, Inc.
• Current Study Sponsor: pharmaand GmbH
• Original Study Sponsor: Clovis Oncology, Inc.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kim Reiss-Binder, MD; University of Pennsylvania

• PRS Account: pharmaand GmbH
• Verification Date: September 2023