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A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor (SEASTAR)

NCT03992131

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).

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
RucaparibRubraca, CO-338Arm A: Oral rucaparib and oral lucitanib
LucitanibCO-3810Arm A: Oral rucaparib and oral lucitanib
Sacituzumab govitecanIMMU-132Arm 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

NameTypeDescriptionInterventions
Arm A: Oral rucaparib and oral lucitanibExperimentalPhase 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.
  • Rucaparib
  • Lucitanib
Arm B: Oral rucaparib and IV sacituzumab govitecanExperimentalPhase 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:Recruiting
Lead Sponsor:Clovis Oncology, Inc.

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