A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy (ATHENA)

• ClinicalTrials.gov Identifier: NCT03522246
• Recruitment Status: Active, not recruiting
• First Posted: May 11, 2018
• Last Update Posted: October 30, 2020
• Sponsor: Clovis Oncology, Inc.
• Collaborators: Bristol-Myers Squibb; Gynecologic Oncology Group; European Network of Gynaecological Oncological Trial Groups (ENGOT); Foundation Medicine
• Information provided by (Responsible Party): Clovis Oncology, Inc.

Tracking Information

• First Submitted Date: April 9, 2018
• First Posted Date: May 11, 2018
• Last Update Posted Date: October 30, 2020
• Actual Study Start Date: May 14, 2018
• Estimated Primary Completion Date: December 30, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 26, 2018): Investigator assessed Progression-free survival (PFS) [ Time Frame: From randomization until disease progression (up to approximately 7 years) ]
• Original Primary Outcome Measures (submitted: April 30, 2018): Investigator assessed Progression-free survival (PFS) [ Time Frame: From randomization until disease progression (up to approximately 10 years) ]

Current Secondary Outcome Measures (submitted: April 30, 2018)

• Blinded independent central review (BICR) PFS [ Time Frame: Every ~12 weeks after the start of combination treatment for ~3 years, then every ~24 weeks thereafter until disease progression. Study data collection expected to last for ~7 years ]
• Overall Survival (OS) [ Time Frame: From enrollment to primary study completion of study (up to approximately 10 years) ]
• Objective response rate (ORR) [ Time Frame: For patients with measurable disease, every ~12 weeks after the start of combination treatment for ~3 years, then every ~24 weeks thereafter until disease progression. Study data collection expected to last for ~7 years ]
• Duration of response (DOR) [ Time Frame: For patients with measurable disease, every ~12 weeks after the start of combination treatment for ~3 years, then every ~24 weeks thereafter until disease progression. Study data collection expected to last for ~7 years ]
• Number of participants with treatment-emergent Adverse Events (AEs) as assessed by CTCAE v4 (or higher) as a measure of safety and tolerability [ Time Frame: Collected from the time patient receives first dose of study drug until post treatment safety follow-up period (up to approximately 10 years) ]
• Number of participants with serious AEs as a measure of safety and tolerability [ Time Frame: Collected from the time patient receives first dose of study drug until post treatment safety follow-up period (up to approximately 10 years) ]
• Number of participants with laboratory abnormalities as a measure of safety and tolerability [ Time Frame: Collected from the time patient receives first dose of study drug until post treatment safety follow-up period (up to approximately 10 years) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy
• Official Title: ATHENA (A Multicenter, Randomized, Double-Blind, Placebo- Controlled Phase 3 Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy)
• Brief Summary: This is a Phase 3, randomized, multinational, double-blind, dual placebo-controlled, 4-arm study evaluating rucaparib and nivolumab as maintenance treatment following response to front-line treatment in newly diagnosed ovarian cancer patients. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-Blind

Primary Purpose: Treatment

Condition

• Epithelial Ovarian Cancer
• Primary Peritoneal
• Fallopian Tube Cancer
• Newly Diagnosed
• FIGO Stage III-IV
• Partial Response
• Complete Response

Intervention

• Drug: Rucaparib
  Oral rucaparib will be administered twice daily
  Other Names:

  • Rubraca
  • CO-338
• Drug: Nivolumab
  IV nivolumab will be administered once every 4 weeks
  Other Names:

  • Opdivo
  • BMS-936558
• Drug: Placebo Oral Tablet
  Placebo tablets will be administered twice daily
• Drug: Placebo IV Infusion
  IV placebo will be administered once every 4 weeks

Study Arms

• Experimental: Arm A
  oral rucaparib + intravenous (IV) nivolumab
  Interventions:

  • Drug: Rucaparib
  • Drug: Nivolumab
• Experimental: Arm B
  oral rucaparib+IV placebo
  Interventions:

  • Drug: Rucaparib
  • Drug: Placebo IV Infusion
• Experimental: Arm C
  oral placebo+ IV nivolumab
  Interventions:

  • Drug: Nivolumab
  • Drug: Placebo Oral Tablet
• Placebo Comparator: Arm D
  Oral placebo + IV placebo
  Interventions:

  • Drug: Placebo Oral Tablet
  • Drug: Placebo IV Infusion

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 29, 2020): 1000
• Original Estimated Enrollment (submitted: April 30, 2018): 1012
• Estimated Study Completion Date: December 30, 2030
• Estimated Primary Completion Date: December 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Newly diagnosed advanced (FIGO stage III-IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy and partial omentectomy, either prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking)
• Completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the Investigator
• Sufficient tumor tissue for planned analysis
• ECOG performance status of 0 or 1
• Patients must be 20 years of age to consent in Japan, Taiwan and South Korea; in all other participating countries patients must be 18 years of age to consent

Exclusion Criteria:

• Pure sarcomas or borderline tumors or mucinous tumors
• Active second malignancy
• Known central nervous system brain metastases
• Any prior treatment for ovarian cancer, other than the first-line platinum regimen
• Evidence of interstitial lung disease or active pneumonitis
• Active, known or suspected autoimmune disease
• Condition requiring active systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Denmark, Finland, Greece, Ireland, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Romania, Russian Federation, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03522246
• Other Study ID Numbers: CO-338-087/GOG-3020/ENGOT-ov45
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: Clovis Oncology, Inc.
• Study Sponsor: Clovis Oncology, Inc.

Collaborators

• Bristol-Myers Squibb
• Gynecologic Oncology Group
• European Network of Gynaecological Oncological Trial Groups (ENGOT)
• Foundation Medicine

Investigators

• Principal Investigator: Bradley Monk, MD, FACS, FACOG; Lead Investigator and Coordinating Investigator for North America
• Principal Investigator: Rebecca Kristeleit, Bsc MBChB FRCP PhD; Coordinating Investigator for Europe and the Middle East
• Principal Investigator: Keiichi Fujiwara, MD, PhD; Lead Investigator for Asia

• PRS Account: Clovis Oncology, Inc.
• Verification Date: October 2020