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A Combination Study of Rucaparib and Atezolizumab in Participants With Advanced Gynecologic Cancers and Triple-Negative Breast Cancer

NCT03101280

Description:

This is a Phase Ib, open-label, non-randomized study in patients with previously treated advanced ovarian or endometrial cancer (Part 1) and platinum-sensitive ovarian cancer or triple-negative breast cancer (TNBC) (Part 2) to investigate the dose, safety, pharmacokinetics, and preliminary efficacy of rucaparib in combination with atezolizumab. The study is conducted in 2 parts: a Dose-Finding Phase (Part 1) and a Dose-Expansion Phase (Part 2)

Related Conditions:
  • Breast Carcinoma
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Fallopian Tube Endometrioid Adenocarcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Ovarian Carcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Combination Study of Rucaparib and Atezolizumab in Participants With Advanced Gynecologic Cancers and Triple-Negative Breast Cancer
  • Official Title: A Phase IB Combination Study of Rucaparib (CO-338) and Atezolizumab (MPDL3280A) in Participants With Advanced Gynecologic Cancers and Triple-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: WO39409
  • SECONDARY ID: 2016-002610-47
  • NCT ID: NCT03101280

Conditions

  • Gynecologic Neoplasms

Interventions

DrugSynonymsArms
AtezolizumabMPDL3280A; TECENTRIQDose-Finding Phase (Part 1): Rucaparib and Atezolizumab
RucaparibCO-338Dose-Finding Phase (Part 1): Rucaparib and Atezolizumab

Purpose

This is a Phase Ib, open-label, non-randomized study in patients with previously treated advanced ovarian or endometrial cancer (Part 1) and platinum-sensitive ovarian cancer or triple-negative breast cancer (TNBC) (Part 2) to investigate the dose, safety, pharmacokinetics, and preliminary efficacy of rucaparib in combination with atezolizumab. The study is conducted in 2 parts: a Dose-Finding Phase (Part 1) and a Dose-Expansion Phase (Part 2)

Trial Arms

NameTypeDescriptionInterventions
Dose-Finding Phase (Part 1): Rucaparib and AtezolizumabExperimentalApproximately 6-18 participants with advanced gynecological cancers will receive different doses of rucaparib administered orally (PO) twice daily (BID) with a fixed dose of atezolizumab (1200 milligrams [mg] intravenously [IV], every 21 days) in 21-day cycles, starting with 400 mg rucaparib BID. The recommended Phase II dose (RP2D), determined by the highest dose level with an acceptable safety profile and with a minimum of 6 participants at which fewer than one-third of participants experience a DLT, was identified as 600 mg rucaparib twice a day (BID).
  • Atezolizumab
  • Rucaparib
Dose-Expansion Phase (Part 2): Rucaparib and AtezolizumabExperimentalTwo tumor-specific expansion cohorts will begin treatment with a 21-day run-in period of rucaparib monotherapy at the specified dose for rucaparib in the potential RP2D identified in Part 1 for the combination. Cohort 1 will have approximately 30 participants with advanced, platinum-sensitive ovarian cancer with tumors harboring a tBRCA mutation [tBCRA(mut)] or BRCA-like molecular signature [tBRCA(wt)/LOH(high)]. Cohort 2 will have approximately 20 participants with previously treated triple-negative breast cancer (TNBC) with a tBRCA mutation [tBCRA(mut)] or BRCA-like molecular signature [tBRCA(wt)/LOH(high)] and have not been exposed to cancer immunotherapies. Following the run in period, participants will receive the combination of rucaparib (specified dose, BID) and atezolizumab (1200 mg IV, every 21 days) in 21-day cycles.
  • Atezolizumab
  • Rucaparib

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  A life expectancy of at least 3 months

          -  Have disease that is measurable as according to RECIST v1.1

          -  Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue
             available for planned analyses

          -  For Part 1, have a histologically confirmed diagnosis of ovarian or endometrial
             cancer, and have received at least one line of prior therapy for metastatic disease

          -  For Part 2 ONLY, have disease that can be safely biopsied

          -  For Part 2 ONLY, have a deleterious germline or somatic breast cancer susceptibility
             gene 1 (BRCA1) or BRCA2 mutation or tumors that are wild-type BRCA but show high
             levels of loss of heterozygosity (LOH) (tBRCAwt/LOHhigh) signature

          -  For Part 2 Cohort 1 (ovarian cancer), high-grade serous or Grade 3 endometrioid
             epithelial ovarian, fallopian tube, or primary peritoneal cancer (PPC)

          -  For Part 2 Cohort 1, have received at least one and no more than two lines of prior
             platinum-containing therapy and progressed after the most recent platinum therapy in a
             platinum-sensitive timeframe

          -  For Part 2 ONLY, Cohort 1, have a CA125 measurement that is greater than 2 times the
             upper limit of normal (ULN)

          -  For Part 2 Cohort 2 (TNBC), metastatic, histologically confirmed estrogen receptor
             (ER)-negative, progesterone receptor-negative, and HER2-negative adenocarcinoma of the
             breast per local laboratory assessment

          -  For Part 2 Cohort 2, radiologic/objective evidence of recurrence or disease
             progression after one line of chemotherapy for TNBC in the metastatic setting

          -  Have adequate organ function

        Exclusion Criteria:

          -  History of prior malignancy except a) curatively treated non-melanoma skin cancer, b)
             solid tumor treated curatively more than 3 years ago without evidence of recurrence,
             c) For Cohort 1 (ovarian cancer): breast cancer with no evidence of disease or
             inactive for at least 3 years, and d) synchronous endometrial cancer (Stage 1A) with
             ovarian cancer

          -  Treatment with chemotherapy, radiation, hormones (except corticosteroids and megestrol
             acetate), or other anticancer therapies less than or equal to (<=) 14 days prior to
             first dose of study treatment

          -  Preexisting duodenal stent and/or any gastrointestinal disorder or defect that would,
             in the opinion of the investigator, interfere with absorption of rucaparib

          -  Symptomatic and/or untreated central nervous system metastases

          -  Prior treatment with any poly adenosine diphosphate−ribose polymerase (PARP) inhibitor
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Adverse Events
Time Frame:Baseline up to approximately 45 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame:Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Objective Response of CR or PR as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (Cancer Antigen 125 [CA125] Response) Considerations
Time Frame:Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Safety Issue:
Description:
Measure:Duration of Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1
Time Frame:Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Safety Issue:
Description:
Measure:DOR as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations
Time Frame:Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) as Determined by Investigator Assessment Using RECIST v1.1
Time Frame:Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Safety Issue:
Description:
Measure:PFS as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations
Time Frame:Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Baseline until Death (up to 45 months)
Safety Issue:
Description:
Measure:Steady State Maximum Plasma Concentration Observed (Cmax) for Rucaparib [Part 1]
Time Frame:Predose (0 hours [hrs]) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)
Safety Issue:
Description:
Measure:Time to Maximum Plasma Concentration (tmax) for Rucaparib [Part 1]
Time Frame:Predose (0 hrs) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curve (AUC) for Rucaparib [Part 1]
Time Frame:Predose (0 hrs) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)
Safety Issue:
Description:
Measure:Apparent Clearance (CL/F) for Rucaparib [Part 1]
Time Frame:Predose (0 hrs) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)
Safety Issue:
Description:
Measure:Minimum Plasma Concentration During the Dosing Interval (Cmin) for Rucaparib [Part 2]
Time Frame:Predose (0 hrs) on Day 1 of Cycles 1-4; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab [Parts 1 and 2]
Time Frame:Predose (0 hrs) on Day 1 of Cycles 1-4, 8 and every 8 cycles (up to 45 months); 0.5 hrs postdose (infusion duration=30-60 minutes) on Day 1 of Cycles 1 and 3; at 30 and 120 days after last dose of study treatment (up to 45 months; cycle length=21 days)
Safety Issue:
Description:
Measure:Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame:Baseline up to approximately 45 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Hoffmann-La Roche

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