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: September 15, 2023
• Sponsor: pharmaand GmbH
• Collaborators: Bristol-Myers Squibb; Gynecologic Oncology Group; European Network of Gynaecological Oncological Trial Groups (ENGOT); Foundation Medicine
• Information provided by (Responsible Party): pharmaand GmbH

Tracking Information

• First Submitted Date: April 9, 2018
• First Posted Date: May 11, 2018
• Last Update Posted Date: September 15, 2023
• 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 *

• Monk BJ, Parkinson C, Lim MC, O'Malley DM, Oaknin A, Wilson MK, Coleman RL, Lorusso D, Bessette P, Ghamande S, Christopoulou A, Provencher D, Prendergast E, Demirkiran F, Mikheeva O, Yeku O, Chudecka-Glaz A, Schenker M, Littell RD, Safra T, Chou HH, Morgan MA, Drochytek V, Barlin JN, Van Gorp T, Ueland F, Lindahl G, Anderson C, Collins DC, Moore K, Marme F, Westin SN, McNeish IA, Shih D, Lin KK, Goble S, Hume S, Fujiwara K, Kristeleit RS. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022 Dec 1;40(34):3952-3964. doi: 10.1200/JCO.22.01003. Epub 2022 Jun 6.
• Monk BJ, Coleman RL, Fujiwara K, Wilson MK, Oza AM, Oaknin A, O'Malley DM, Lorusso D, Westin SN, Safra T, Herzog TJ, Marme F, N Eskander R, Lin KK, Shih D, Goble S, Grechko N, Hume S, Maloney L, McNeish IA, Kristeleit RS. ATHENA (GOG-3020/ENGOT-ov45): a randomized, phase III trial to evaluate rucaparib as monotherapy (ATHENA-MONO) and rucaparib in combination with nivolumab (ATHENA-COMBO) as maintenance treatment following frontline platinum-based chemotherapy in ovarian cancer. Int J Gynecol Cancer. 2021 Dec;31(12):1589-1594. doi: 10.1136/ijgc-2021-002933. Epub 2021 Sep 30.

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, Czechia, Denmark, Finland, Germany, Greece, Ireland, Israel, Italy, Japan, Korea, Republic of, New Zealand, Poland, Romania, Russian Federation, Singapore, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03522246
• Other Study ID Numbers: CO-338-087/GOG-3020/ENGOT-ov45; 2017-004557-17 ( EudraCT Number )
• 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
• Current Responsible Party: pharmaand GmbH
• Original Responsible Party: Clovis Oncology, Inc.
• Current Study Sponsor: pharmaand GmbH
• Original Study Sponsor: Clovis Oncology, Inc.

Collaborators

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

• Investigators: Not Provided
• PRS Account: pharmaand GmbH
• Verification Date: September 2023