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

Ovarian Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03992131
• Other study ID #: CO-338-098
• Secondary ID: 2018-003759-39
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 28, 2019
• Est. completion date: April 22, 2022

Study information

• Verified date: January 2024
• Source: pharmaand GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: April 22, 2022
• Est. primary completion date: March 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Rucaparib
Rucaparib will be administered per schedule specified in the arm description.
• Lucitanib
Lucitanib will be administered per schedule specified in the arm description.
• Sacituzumab govitecan
Sacituzumab govitecan will be administered per schedule specified in the arm description.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
pharmaand GmbH	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years
Secondary	Duration of Response (DOR) (Phase 2)	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.	From the date of first best response to disease progression or death, whichever occurs first, assessed up to 2 years
Secondary	Progression-free Survival (PFS) (Phase 2)	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.	From the first dose of study drug to documented radiographic progression or death, whichever occurs first, assessed up to 2 years
Secondary	Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b)	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.	From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years