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

Phase 2TerminatedNCT03992131

pharmaand GmbH25 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ovarian Cancer Triple-negative Breast Cancer Urothelial Carcinoma Solid Tumor

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Outcomes

Primary Outcomes

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.

Time frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years

Secondary Outcomes

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.

Time frame: From the date of first best response to disease progression or death, whichever occurs first, assessed up to 2 years

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.

Time frame: From the first dose of study drug to documented radiographic progression or death, whichever occurs first, assessed up to 2 years

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.

Time frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years