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

• ClinicalTrials.gov Identifier: NCT03992131
• Recruitment Status: Terminated
• First Posted: June 20, 2019
• Results First Posted: January 16, 2024
• Last Update Posted: January 16, 2024
• Sponsor: pharmaand GmbH
• Collaborator: Gilead Sciences
• Information provided by (Responsible Party): pharmaand GmbH

Tracking Information

• First Submitted Date: June 4, 2019
• First Posted Date: June 20, 2019
• Results First Submitted Date: December 4, 2023
• Results First Posted Date: January 16, 2024
• Last Update Posted Date: January 16, 2024
• Actual Study Start Date: June 28, 2019
• Actual Primary Completion Date: March 8, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 4, 2023)

Number of Participants With Objective Response, as Assessed by the Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 (Phase 2) [ Time Frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years ]

Objective response was defined as a documented and confirmed best overall response of complete response (CR) or partial response (PR) as assessed by the investigator. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeters (mm); and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Original Primary Outcome Measures (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)

Current Secondary Outcome Measures (submitted: December 4, 2023)

• Duration of Response (DOR) (Phase 2) [ Time Frame: From the date of first best response to disease progression or death, whichever occurs first, assessed up to 2 years ]
  Duration of response was measured from the date that best response (CR or PR) was first recorded until the first date that disease progression was documented per RECIST v1.1. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm; and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression.
• Progression-free Survival (PFS) (Phase 2) [ Time Frame: From the first dose of study drug to documented radiographic progression or death, whichever occurs first, assessed up to 2 years ]
  PFS was measured as the 1+ the number of days from the first dose of study drug to documented radiographic progression, according to RECIST v1.1, as determined by the investigator, or death due to any cause, whichever occurred first. Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression.
• Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) [ Time Frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years ]
  Objective response was defined as a documented and confirmed best overall response of CR or PR as assessed by the investigator. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm; and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Original Secondary Outcome Measures (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)

• 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 Combination With Other Anticancer Agents in Participants 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
• Brief Summary: This is an open label, Phase 1b/2 study with multiple treatment arms evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of rucaparib in combination with a second anticancer therapy in participants with an advanced/metastatic solid malignancy (Phase 1b), followed by evaluation of the combination in one or more specific participant populations in an expansion phase (Phase 2 cohorts).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Ovarian Cancer
• Triple-negative Breast Cancer
• Urothelial Carcinoma
• Solid Tumor

Intervention

• Drug: Rucaparib
  Rucaparib will be administered per schedule specified in the arm description.
  Other Names:

  • Rubraca
  • CO-338
• Drug: Lucitanib
  Lucitanib will be administered per schedule specified in the arm description.
  Other Name: CO-3810
• Drug: Sacituzumab govitecan
  Sacituzumab govitecan will be administered per schedule specified in the arm description.
  Other Name: IMMU-132

Study Arms

• Experimental: Arm A: Rucaparib and Lucitanib
  Participants will receive oral rucaparib twice daily (BID) and oral lucitanib once daily (QD) continuously in 28-day cycles.
  Interventions:

  • Drug: Rucaparib
  • Drug: Lucitanib
• Experimental: Arm B: Rucaparib BID and Sacituzumab Govitecan
  Participants will receive oral rucaparib BID, administered continuously, in combination with intravenous (IV) sacituzumab govitecan administration on Day 1 and Day 8 of a 21-day cycle.
  Interventions:

  • Drug: Rucaparib
  • Drug: Sacituzumab govitecan
• Experimental: Arm B: Rucaparib QD and Sacituzumab Govitecan
  Participants will receive oral rucaparib QD, administered continuously, in combination with IV sacituzumab govitecan administration on Day 1 and Day 8 of a 21-day cycle.
  Interventions:

  • Drug: Rucaparib
  • Drug: Sacituzumab govitecan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 26, 2022): 25
• Original Estimated Enrollment (submitted: June 18, 2019): 329
• Actual Study Completion Date: April 22, 2022
• Actual Primary Completion Date: March 8, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria Phase 1b (all arms):

• Solid tumor, advanced or metastatic, progressed on standard treatment participants 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
• Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Tumor tissue for genomic analysis

Exclusion Criteria Phase 1b (all arms):

• Known history of myelodysplastic syndrome (MDS)
• Symptomatic and/or untreated central nervous system (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 poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor treatment allowed for participants with ovarian cancer
• Known history of MDS
• Symptomatic and/or untreated CNS metastases

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: NCT03992131
• Other Study ID Numbers: CO-338-098; 2018-003759-39 ( EudraCT Number )
• 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: Not Provided
• Current Responsible Party: pharmaand GmbH
• Original Responsible Party: Clovis Oncology, Inc.
• Current Study Sponsor: pharmaand GmbH
• Original Study Sponsor: Clovis Oncology, Inc.
• Collaborators: Gilead Sciences
• Investigators: Not Provided
• PRS Account: pharmaand GmbH
• Verification Date: January 2024