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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03101280




Registration number
NCT03101280
Ethics application status
Date submitted
3/04/2017
Date registered
5/04/2017
Date last updated
22/10/2020

Titles & IDs
Public title
A Combination Study of Rucaparib and Atezolizumab in Participants With Advanced Gynecologic Cancers and Triple-Negative Breast Cancer
Scientific title
A Phase IB Combination Study of Rucaparib (CO-338) and Atezolizumab (MPDL3280A) in Participants With Advanced Gynecologic Cancers and Triple-Negative Breast Cancer
Secondary ID [1] 0 0
2016-002610-47
Secondary ID [2] 0 0
WO39409
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gynecologic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Rucaparib

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

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


Treatment: Drugs: Atezolizumab
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.

Treatment: Drugs: Rucaparib
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events
Timepoint [1] 0 0
Baseline up to approximately 45 months
Primary outcome [2] 0 0
Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]
Timepoint [2] 0 0
Cycle 1 (Day 1 up to Day 21)
Primary outcome [3] 0 0
Recommended Phase II Dose (RP2D) of Rucaparib for the Combination [Part 1]
Timepoint [3] 0 0
Cycle 1 (Day 1 up to Day 21)
Primary outcome [4] 0 0
Number of Dose Modifications due to Adverse Events [Part 2]
Timepoint [4] 0 0
Baseline up to approximately 45 months
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Secondary outcome [3] 0 0
Duration of Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1
Timepoint [3] 0 0
Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Secondary outcome [4] 0 0
DOR as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations
Timepoint [4] 0 0
Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Secondary outcome [5] 0 0
Progression-Free Survival (PFS) as Determined by Investigator Assessment Using RECIST v1.1
Timepoint [5] 0 0
Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Secondary outcome [6] 0 0
PFS as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations
Timepoint [6] 0 0
Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
Secondary outcome [7] 0 0
Overall Survival
Timepoint [7] 0 0
Baseline until Death (up to 45 months)
Secondary outcome [8] 0 0
Steady State Maximum Plasma Concentration Observed (Cmax) for Rucaparib [Part 1]
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Time to Maximum Plasma Concentration (tmax) for Rucaparib [Part 1]
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Area Under the Plasma Concentration-Time Curve (AUC) for Rucaparib [Part 1]
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Apparent Clearance (CL/F) for Rucaparib [Part 1]
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Minimum Plasma Concentration During the Dosing Interval (Cmin) for Rucaparib [Part 2]
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Serum Concentration of Atezolizumab [Parts 1 and 2]
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [14] 0 0
Baseline up to approximately 45 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/08/2020
Sample size
Target
Accrual to date
Final
29
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Lyon
Country [2] 0 0
France
State/province [2] 0 0
Pierre Benite
Country [3] 0 0
France
State/province [3] 0 0
Villejuif CEDEX
Country [4] 0 0
Spain
State/province [4] 0 0
Navarra
Country [5] 0 0
Spain
State/province [5] 0 0
Barcelona
Country [6] 0 0
Spain
State/province [6] 0 0
Madrid
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Preston
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/ct2/show/NCT03101280
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03101280