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

Primary Purpose

Gynecologic Neoplasms

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Atezolizumab

Rucaparib

About this trial

This is an interventional treatment trial for Gynecologic Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Peter Maccallum Cancer Centre
Centre Leon Berard
Centre Hospitalier Lyon Sud; Service d'Oncologie Médicale
Gustave Roussy
Clínica Universidad de Navarra
Hospital Universitario Vall d'Hebron
La Paz University Hospital
Royal Marsden Hospital - London
University College London Hospitals NHS Foundation Trust - University College Hospital
Lancashire Teaching Hospitals NHS Foundation Trust
Royal Marsden NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dose-Finding Phase (Part 1): Rucaparib and Atezolizumab

Dose-Expansion Phase (Part 2): Rucaparib and Atezolizumab

Arm Description

Approximately 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).

Two 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.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Events

Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]

Recommended Phase II Dose (RP2D) of Rucaparib for the Combination [Part 1]

Number of Dose Modifications due to Adverse Events [Part 2]

Secondary Outcome Measures

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)

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

Duration of Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1

DOR as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations

Progression-Free Survival (PFS) as Determined by Investigator Assessment Using RECIST v1.1

PFS as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations

Overall Survival

Steady State Maximum Plasma Concentration Observed (Cmax) for Rucaparib [Part 1]

Time to Maximum Plasma Concentration (tmax) for Rucaparib [Part 1]

Area Under the Plasma Concentration-Time Curve (AUC) for Rucaparib [Part 1]

Apparent Clearance (CL/F) for Rucaparib [Part 1]

Minimum Plasma Concentration During the Dosing Interval (Cmin) for Rucaparib [Part 2]

Serum Concentration of Atezolizumab [Parts 1 and 2]

Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab

Full Information

NCT ID

NCT03101280

First Posted

April 3, 2017

Last Updated

October 20, 2020

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT03101280

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

April 27, 2017 (Actual)

Primary Completion Date

August 11, 2020 (Actual)

Study Completion Date

August 11, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gynecologic Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose-Finding Phase (Part 1): Rucaparib and Atezolizumab

Arm Type

Experimental

Arm Description

Arm Title

Dose-Expansion Phase (Part 2): Rucaparib and Atezolizumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Atezolizumab

Other Intervention Name(s)

MPDL3280A; TECENTRIQ

Intervention Description

Atezolizumab 1200 mg (equivalent to an average body weight-based dose of 15 milligrams per kilogram [mg/kg]) will be administered by IV infusion once every 3 weeks, corresponding to a 21-day treatment cycle. Participants will receive atezolizumab starting on Cycle 1, Day 1. Participants deriving clinical benefit will be allowed to continue on study treatment until the absence of unacceptable toxicity or compelling evidence of disease progression.

Intervention Type

Drug

Intervention Name(s)

Rucaparib

Other Intervention Name(s)

CO-338

Intervention Description

The starting dosage level of rucaparib for Part 1 is 400 mg PO BID during a 21-day treatment cycle. During Part 1, the rucaparib doses were increased up to a maximum of 600 mg PO BID using a standard 3 + 3 dose escalation. RP2D was identified as 600 mg BID. During Part 2 of the study, rucaparib will be dosed at the RP2D determined in Part 1. Participants in Part 1 of the study will receive rucaparib starting on Cycle 1, Day 1. During Part 2, participants will receive rucaparib monotherapy during a 21-day run-in period. After completion of the rucaparib run-in period and the first on-treatment biopsy between Days 15 and 21 of the run-in period, participants will begin Cycle 1, Day 1 of the rucaparib. Participants deriving clinical benefit will be allowed to continue on study treatment until the absence of unacceptable toxicity or compelling evidence of disease progression.

Primary Outcome Measure Information:

Title

Percentage of Participants With Adverse Events

Time Frame

Baseline up to approximately 45 months

Title

Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]

Time Frame

Cycle 1 (Day 1 up to Day 21)

Title

Recommended Phase II Dose (RP2D) of Rucaparib for the Combination [Part 1]

Time Frame

Cycle 1 (Day 1 up to Day 21)

Title

Number of Dose Modifications due to Adverse Events [Part 2]

Time Frame

Baseline up to approximately 45 months

Secondary Outcome Measure Information:

Title

Time Frame