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出境医 / 临床实验 / A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor (SEASTAR)

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

Study Description
Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Ovarian Cancer Triple-negative Breast Cancer Urothelial Carcinoma Solid Tumor Drug: Rucaparib Drug: Lucitanib Drug: Sacituzumab govitecan Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 329 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 28, 2019
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : March 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: Arm A: Oral rucaparib and oral lucitanib

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.

 Drug: Rucaparib
Oral rucaparib will be administered twice daily
Other Names:
  • Rubraca
  • CO-338

Drug: Lucitanib
Oral lucitanib will be administered once daily
Other Name: CO-3810
Experimental: Arm B: Oral rucaparib and IV sacituzumab govitecan

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

 Drug: Rucaparib
Oral rucaparib will be administered twice daily
Other Names:
  • Rubraca
  • CO-338

Drug: Sacituzumab govitecan
IV Sacituzumab govitecan will be administered Days 1 and 8 every 21 days
Other Name: IMMU-132
Outcome Measures
Primary Outcome Measures :
  1. 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. ]
    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)

  2. Number of participants who experience dose limiting toxicity as defined in the protocol. (Phase 1b) [ Time Frame: Up to 2 years ]
    The highest dose level at which less than 2 of 6 participants or less than 33% of participants experience a dose limiting toxicity will be considered the maximum tolerated dose / recommended phase 2 dose.

  3. Overall Response Rate (Phase 2) [ Time Frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years. ]
    Preliminary overall response rate (ORR) defined as the proportion of patients with a best overall response of CR or PR according to RECIST 1.1 (Phase 1b)


Secondary Outcome Measures :
  1. 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. ]
  2. 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. ]
  3. 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 ]
    Evaluation of individual responses to study treatment according to RECIST 1.1.

  4. 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 ]
    PK Rucaparib (Phase 1b)

  5. Cmax - max concentration [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)

  6. Tmax - time to max concentration [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)

  7. T1/2 - elimination half-life [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)

  8. k el - elimination rate constant [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)

  9. 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 ]
    PK Rucaparib (Phase 1b)

  10. Cl/F - total plasma clearance [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Locations
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United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Clovis Oncology, Inc.
Gilead Sciences
Tracking Information
First Submitted Date  ICMJE June 4, 2019
First Posted Date  ICMJE June 20, 2019
Last Update Posted Date April 13, 2021
Actual Study Start Date  ICMJE June 28, 2019
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2019)
  • 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. ]
    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)
  • Number of participants who experience dose limiting toxicity as defined in the protocol. (Phase 1b) [ Time Frame: Up to 2 years ]
    The highest dose level at which less than 2 of 6 participants or less than 33% of participants experience a dose limiting toxicity will be considered the maximum tolerated dose / recommended phase 2 dose.
  • Overall Response Rate (Phase 2) [ Time Frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years. ]
    Preliminary overall response rate (ORR) defined as the proportion of patients with a best overall response of CR or PR according to RECIST 1.1 (Phase 1b)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2019)
  • 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. ]
  • 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. ]
  • 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 ]
    Evaluation of individual responses to study treatment according to RECIST 1.1.
  • 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 ]
    PK Rucaparib (Phase 1b)
  • Cmax - max concentration [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)
  • Tmax - time to max concentration [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)
  • T1/2 - elimination half-life [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)
  • k el - elimination rate constant [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)
  • 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 ]
    PK Rucaparib (Phase 1b)
  • Cl/F - total plasma clearance [ Time Frame: First dose of study drug through at least 28 days after end of treatment ]
    PK Rucaparib (Phase 1b)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor (SEASTAR)
Official Title  ICMJE 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
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Cancer
  • Triple-negative Breast Cancer
  • Urothelial Carcinoma
  • Solid Tumor
Intervention  ICMJE
  • Drug: Rucaparib
    Oral rucaparib will be administered twice daily
    Other Names:
    • Rubraca
    • CO-338
  • Drug: Lucitanib
    Oral lucitanib will be administered once daily
    Other Name: CO-3810
  • Drug: Sacituzumab govitecan
    IV Sacituzumab govitecan will be administered Days 1 and 8 every 21 days
    Other Name: IMMU-132
Study Arms  ICMJE
  • Experimental: Arm A: Oral rucaparib and oral lucitanib

    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.

    Interventions:
    • Drug: Rucaparib
    • Drug: Lucitanib
  • Experimental: Arm B: Oral rucaparib and IV sacituzumab govitecan

    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

    Interventions:
    • Drug: Rucaparib
    • Drug: Sacituzumab govitecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 18, 2019) 		329
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03992131
Other Study ID Numbers  ICMJE CO-338-098
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  ICMJE Not Provided
Responsible Party Clovis Oncology, Inc.
Study Sponsor  ICMJE Clovis Oncology, Inc.
Collaborators  ICMJE Gilead Sciences
Investigators  ICMJE Not Provided
PRS Account Clovis Oncology, Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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