Clinical trial NCT03101280: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gynecologic Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-04-05
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to approximately 45 months
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]
timeFrame: Cycle 1 (Day 1 up to Day 21)
measure: Recommended Phase II Dose (RP2D) of Rucaparib for the Combination [Part 1]
timeFrame: Cycle 1 (Day 1 up to Day 21)
measure: Number of Dose Modifications due to Adverse Events [Part 2]
timeFrame: Baseline up to approximately 45 months
Secondary outcomes:
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)
timeFrame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
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
timeFrame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
measure: Duration of Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1
timeFrame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
measure: DOR as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations
timeFrame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
measure: Progression-Free Survival (PFS) as Determined by Investigator Assessment Using RECIST v1.1
timeFrame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
measure: PFS as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations
timeFrame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)
measure: Overall Survival
timeFrame: Baseline until Death (up to 45 months)
measure: Steady State Maximum Plasma Concentration Observed (Cmax) for Rucaparib [Part 1]
timeFrame: 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)
measure: Time to Maximum Plasma Concentration (tmax) for Rucaparib [Part 1]
timeFrame: 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)
measure: Area Under the Plasma Concentration-Time Curve (AUC) for Rucaparib [Part 1]
timeFrame: 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)
measure: Apparent Clearance (CL/F) for Rucaparib [Part 1]
timeFrame: 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)
measure: Minimum Plasma Concentration During the Dosing Interval (Cmin) for Rucaparib [Part 2]
timeFrame: 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)
measure: Serum Concentration of Atezolizumab [Parts 1 and 2]
timeFrame: 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)
measure: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
timeFrame: Baseline up to approximately 45 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Lyon
country: France
facility: Centre Leon Berard
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud; Service d'Oncologie Médicale
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: La Paz University Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital - London
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - University College Hospital
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: