Description:
This is an open label, Phase 1b/2 study with multiple treatment arms evaluating the safety,
tolerability, PK, and preliminary efficacy of rucaparib in combination with a second
anticancer therapy in patients with an advanced/metastatic solid malignancy (Phase 1b),
followed by evaluation of the combination in one or more specific patient populations in an
expansion phase (Phase 2 cohorts).
Title
- Brief Title: A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor (SEASTAR)
- Official Title: SEASTAR: A Phase 1b/2, Open-label, Parallel Arm Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor
Clinical Trial IDs
- ORG STUDY ID:
CO-338-098
- NCT ID:
NCT03992131
Conditions
- Ovarian Cancer
- Triple-negative Breast Cancer
- Urothelial Carcinoma
- Solid Tumor
Interventions
Drug | Synonyms | Arms |
---|
Rucaparib | Rubraca, CO-338 | Arm A: Oral rucaparib and oral lucitanib |
Lucitanib | CO-3810 | Arm A: Oral rucaparib and oral lucitanib |
Sacituzumab govitecan | IMMU-132 | Arm B: Oral rucaparib and IV sacituzumab govitecan |
Purpose
This is an open label, Phase 1b/2 study with multiple treatment arms evaluating the safety,
tolerability, PK, and preliminary efficacy of rucaparib in combination with a second
anticancer therapy in patients with an advanced/metastatic solid malignancy (Phase 1b),
followed by evaluation of the combination in one or more specific patient populations in an
expansion phase (Phase 2 cohorts).
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: Oral rucaparib and oral lucitanib | Experimental | Phase 1b (Dose escalation): Up to 55 patients with advanced or metastatic solid tumors.
Phase 2 (Dose expansion): Up to 80 patients with High Grade Ovarian Cancer. | |
Arm B: Oral rucaparib and IV sacituzumab govitecan | Experimental | Phase 1b (Dose escalation): Up to 55 patients with metastatic Triple Negative Breast Cancer, metastatic Urothelial Cancer, platinum resistant Ovarian Cancer, or a tumor with a BRCA1, BRCA2, PALB2, RAD51C, or RAD5/1D mutation
Phase 2 (Dose expansion): Up to 139 patients with metastatic Triple Negative Breast Cancer, metastatic Urothelial Cancer, or platinum resistant Ovarian Cancer | - Rucaparib
- Sacituzumab govitecan
|
Eligibility Criteria
Inclusion Criteria Phase 1b (all arms):
- Solid tumor, advanced or metastatic, progressed on standard treatment Patients in Arm
B must have either triple negative breast cancer OR urothelial carcinoma OR ovarian
cancer OR have a solid tumor with a deleterious mutation in BRCA1, BRCA2, PALB2,
RAD51C or RAD51D
- Measurable disease per RECIST v1.1
- Adequate organ function
- ECOG 0 or 1
- Tumor tissue for genomic analysis
Exclusion Criteria Phase 1b (all arms):
- Known history of MDS
- Symptomatic and/or untreated CNS metastases
Inclusion Criteria Phase 2 (all arms):
- Histologically or cytologically confirmed solid tumor, previously treated and
measurable per RECIST v1.1, as follows:
- Arm A: ovarian cancer with gBRCAwt disease, either platinum-sensitive OR
platinum-resistant
- Arm B: Metastatic triple negative breast cancer OR advanced/ metastatic urothelial
carcinoma OR relapsed ovarian cancer
- At least 1 prior line of standard therapy for advanced disease
- Adequate organ function
- ECOG 0 or 1
- Tumor tissue for genomic analysis
Exclusion Criteria Phase 2 (all arms):
- Prior PARPi treatment allowed for patients with ovarian cancer
- Known history of MDS
- Symptomatic and/or untreated CNS metastases
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) |
Time Frame: | First dose of study drug through at least 28 days after end of treatment. |
Safety Issue: | |
Description: | Number of participants with treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs) as assessed by CTCAE v5.0 as a measure of safety and tolerability (Phase 1b) |
Secondary Outcome Measures
Measure: | Duration of Response (Phase 2) |
Time Frame: | DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first, assessed up to 2 years. |
Safety Issue: | |
Description: | |
Measure: | Progression-free survival (PFS) |
Time Frame: | PFS defined as 1+ the number of days from the first dose of study drug to documented radiographic progression or death, assessed up to 2 years. |
Safety Issue: | |
Description: | |
Measure: | Objective Response (Phase 1b) |
Time Frame: | From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years |
Safety Issue: | |
Description: | Evaluation of individual responses to study treatment according to RECIST 1.1. |
Measure: | Concentration AUC - area under curve from time zero to time t or infinity |
Time Frame: | First dose of study drug through at least 28 days after end of treatment |
Safety Issue: | |
Description: | PK Rucaparib (Phase 1b) |
Measure: | Cmax - max concentration |
Time Frame: | First dose of study drug through at least 28 days after end of treatment |
Safety Issue: | |
Description: | PK Rucaparib (Phase 1b) |
Measure: | Tmax - time to max concentration |
Time Frame: | First dose of study drug through at least 28 days after end of treatment |
Safety Issue: | |
Description: | PK Rucaparib (Phase 1b) |
Measure: | T1/2 - elimination half-life |
Time Frame: | First dose of study drug through at least 28 days after end of treatment |
Safety Issue: | |
Description: | PK Rucaparib (Phase 1b) |
Measure: | k el - elimination rate constant |
Time Frame: | First dose of study drug through at least 28 days after end of treatment |
Safety Issue: | |
Description: | PK Rucaparib (Phase 1b) |
Measure: | Vss/F - volume of distribution at steady state after non-intravenous administration; Cl/F - total plasma clearance |
Time Frame: | First dose of study drug through at least 28 days after end of treatment |
Safety Issue: | |
Description: | PK Rucaparib (Phase 1b) |
Measure: | Cl/F - total plasma clearance |
Time Frame: | First dose of study drug through at least 28 days after end of treatment |
Safety Issue: | |
Description: | PK Rucaparib (Phase 1b) |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Clovis Oncology, Inc. |
Last Updated
April 13, 2021