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

A Phase 2 Multicenter, Open-label Study of Rucaparib as Treatment for Solid Tumors Associated With Deleterious Mutations in Homologous Recombination Repair Genes

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04171700

Acronym

LODESTAR

Enrollment

Registered

2019-11-21

Start date

2020-01-16

Completion date

2022-07-15

Last updated

2023-10-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid Tumor

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

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.

Interventions

DRUGRucaparib

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Best Overall Response Rate by Investigator	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).

Secondary

Measure	Time frame	Description
Duration of Response	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	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	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 Response Rate by Independent Radiology Review	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).
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]	From first dose of study drug until disease progression (up to approximately 2 years)	Rucaparib pharmacokinetics
Overall Survival	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.

Countries

United States

Participant flow

Recruitment details

A total of 83 participants were enrolled across 19 US sites between January 2020 and March 2022. 63 participants were enrolled in cohort A and 20 in cohort B. Cohort A comprised participants with a deleterious mutation in one of the following genes; BRCA1, BRCA2, PALB2, RAD51C, RAD51D. Cohort B comprised participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, RAD51B.

Participants by arm

Arm	Count
Rucaparib Cohort A Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.	63
Rucaparib Cohort B Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.	20
Total	83

Baseline characteristics

Characteristic	Rucaparib Cohort A	Rucaparib Cohort B	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	30 Participants	12 Participants	42 Participants
Age, Categorical Between 18 and 65 years	33 Participants	8 Participants	41 Participants
Age, Continuous	64.7 Years STANDARD_DEVIATION 10.85	65.2 Years STANDARD_DEVIATION 13.38	64.8 Years STANDARD_DEVIATION 11.43
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	0 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants	20 Participants	81 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) Black or African American	5 Participants	0 Participants	5 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	56 Participants	19 Participants	75 Participants
Region of Enrollment United States	63 participants	20 participants	83 participants
Sex: Female, Male Female	36 Participants	14 Participants	50 Participants
Sex: Female, Male Male	27 Participants	6 Participants	33 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	23 / 63	10 / 20
other Total, other adverse events	63 / 63	19 / 20
serious Total, serious adverse events	13 / 63	5 / 20

Outcome results

Primary

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).