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

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ClinicalTrials.gov Identifier: NCT03101280
Recruitment Status : Recruiting
First Posted : April 5, 2017
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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)

Condition or disease Intervention/treatment Phase
Gynecologic Neoplasms Drug: Atezolizumab Drug: Rucaparib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 4, 2017
Estimated Primary Completion Date : January 30, 2019
Estimated Study Completion Date : January 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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).
Drug: 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.
Other Name: MPDL3280A; TECENTRIQ

Drug: 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.
Other Name: CO-338

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.

Drug: 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.
Other Name: MPDL3280A; TECENTRIQ

Drug: 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.
Other Name: CO-338




Primary Outcome Measures :
  1. Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 45 months ]
  2. Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Part 1] [ Time Frame: Cycle 1 (Day 1 up to Day 21) ]
  3. Recommended Phase II Dose (RP2D) of Rucaparib for the Combination [Part 1] [ Time Frame: Cycle 1 (Day 1 up to Day 21) ]
  4. Number of Dose Modifications due to Adverse Events [Part 2] [ Time Frame: Baseline up to approximately 45 months ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. Overall Survival [ Time Frame: Baseline until Death (up to 45 months) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  • 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) 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03101280


Contacts
Contact: Reference Study ID Number: WO39409 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Australia, Victoria
Peter Maccallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
France
Centre Leon Berard Recruiting
Lyon, France, 69008
Gustave Roussy Not yet recruiting
Villejuif CEDEX, France, 94800
Spain
Clínica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31620
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain, 08035
La Paz University Hospital Recruiting
Madrid, Spain
United Kingdom
Royal Marsden Hospital - London Recruiting
London, United Kingdom, SW3 6JJ
University College London Hospitals NHS Foundation Trust - University College Hospital Recruiting
London, United Kingdom, WC1E 6AU
Lancashire Teaching Hospitals NHS Foundation Trust Not yet recruiting
Preston, United Kingdom, PR2 9HT
Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03101280     History of Changes
Other Study ID Numbers: WO39409
2016-002610-47 ( EudraCT Number )
First Posted: April 5, 2017    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Triple Negative Breast Neoplasms
Genital Neoplasms, Female
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Urogenital Neoplasms
Atezolizumab
Rucaparib
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action