A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy
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.
Key Facts
Lead Sponsor
pharmaand GmbH
Enrollment
1097
Start Date
2018-05-14
Completion Date
2024-05-20
Study Type
INTERVENTIONAL
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)
Interventions
Conditions
Eligibility
Age Range
18 Years+
Sex
FEMALE
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
Outcome Measures
Primary Outcomes
Monotherapy Arm B and Arm D: Investigator Assessed Progression-free Survival (PFS)
PFS by investigator was defined as the time from randomization to disease progression, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Monotherapy Arm B and Arm D: Investigator Assessed PFS
PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Combination Therapy Arm A and Arm B: Investigator Assessed PFS
PFS by investigator was defined as the time from randomization to disease progression, according to RECIST v1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months)
Secondary Outcomes
Monotherapy Arm B and Arm D: Blinded Independent Central Review (BICR) PFS
PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Monotherapy Arm B and Arm D: BICR PFS
PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Combination Therapy Arm A and Arm B: BICR PFS
PFS was assessed by BICR per RECIST v1.1 as the time from randomization to disease progression, or death due to any cause, whichever occurred first. Progressive disease was defined as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months)
Monotherapy Arm B and Arm D: Overall Survival (OS)
OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Time frame: From randomization until death due to any cause (up to the primary data analysis at approximately 36 months)
Monotherapy Arm B and Arm D: OS
OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Time frame: From randomization until death due to any cause (up to the primary data analysis at approximately 40 months)
Combination Therapy Arm A and Arm B: OS
OS was defined as the number of days (measured in months) from the date of randomization to the date of death due to any cause.
Time frame: From randomization until death due to any cause (up to the combination therapy interim analysis at approximately 72 months)
Monotherapy Arm B and Arm D: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Monotherapy Arm B and Arm D: ORR
ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization until disease progression (up to the primary data analysis at approximately 39 months)
Combination Therapy Arm A and Arm B: ORR
ORR was defined as the percentage of participants with CR or PR as assessed by the Investigator per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization until disease progression (up to the combination therapy interim analysis at approximately 66 months)
Monotherapy Arm B and Arm D: Duration of Response (DOR)
DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of progressive disease (PD) or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From first confirmed response until disease progression (up to the primary data analysis at approximately 30 months)
Monotherapy Arm B and Arm D: DOR
DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From first confirmed response until disease progression (up to the primary data analysis at approximately 33 months)
Combination Therapy Arm A and Arm B: DOR
DOR was assessed by the investigator and defined as the interval from the first documentation of objective response (CR or PR per RECIST v1.1) to the earlier of the first documentation of PD or death from any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD: 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Time frame: From first confirmed response until disease progression (up to the combination therapy interim analysis at approximately 60 months)
Locations
Arizona Oncology Associates, PC - HAL, Phoenix, United States
Arizona Oncology Associates, PC - HOPE, Tucson, United States
The University of Arizona Cancer Center, Tucson, United States
John Muir Clinical Research Center, Concord, United States
UCLA Women's Health Clinical Research Unit, Los Angeles, United States
Kaiser Permanente Northern California, San Francisco, United States
University of Colorado Cancer Center, Aurora, United States
Rocky Mountain Cancer Centers, Lakewood, United States
Yale University, New Haven, United States
Florida Gynecologic Oncology, Fort Myers, United States
MD Anderson Cancer Center-Baptist, Jacksonville, United States
Baptist Health Medical Group Oncology, LLC, Miami, United States
Florida Hospital, Orlando, United States
Northside Hospital, Atlanta, United States
Augusta University, Augusta, United States
Rush University Medical Center, Chicago, United States
Dr. Sudarshan K. Sharma, Ltd - Gynecologic Oncology, Hinsdale, United States
Ferrell-Duncan Clinic, Springfield, United States
Community Health Network, Indianapolis, United States
University of Iowa Hospitals, Iowa City, United States
University of Kansas Cancer Center, Westwood, United States
University of Kentucky, Lexington, United States
Norton Cancer Institute, Louisville, United States
Ochsner Medical Center, New Orleans, United States
Maine Medical Center, Scarborough, United States
SKCCC at Johns Hopkins, Baltimore, United States
Massachusetts General Hospital, Boston, United States
Karmanos Cancer Institute, Detroit, United States
Metro Minnesota Community Oncology Research Consortium, Saint Louis Park, United States
Washington University School of Medicine, St Louis, United States
Women's Cancer Center of Nevada, Las Vegas, United States
MD Anderson Cancer Center at Cooper, Camden, United States
Summit Medical Group, Florham Park, United States
Women's Cancer Care Associates, Albany, United States
Broome Oncology, LLC, Johnson City, United States
Northwell Health Monter Cancer Center, Lake Success, United States
New York University Medical Center, New York, United States
University of North Carolina, Chapel Hill, United States
University of Cincinnati, Cincinnati, United States
Oncology Hematology Care, Inc, Cincinnati, United States
Cleveland Clinic, Cleveland, United States
The Ohio State University, Columbus, United States
MD Anderson Cancer Center - Ohio Health, Columbus, United States
University of Oklahoma Health Science Center, Oklahoma City, United States
Oklahoma Cancer Specialists and Research Institute, Tulsa, United States
Oncology Associates of Oregon, P.C., Eugene, United States
LMG Gynecologic Oncology, Portland, United States
Northwest Cancer Specialists, P.C., Portland, United States
University of Pennsylvania, Philadelphia, United States
Thomas Jefferson University, Philadelphia, United States
UPMC Magee-Womens Hospital, Pittsburgh, United States
Abington Memorial Hospital, Willow Grove, United States
Avera Gynecologic Oncology, Sioux Falls, United States
Texas Oncology - Austin Central, Austin, United States
Texas Oncology - Bedford, Bedford, United States
Texas Oncology - Dallas Presbyterian Hospital, Dallas, United States
Texas Oncology - Fort Worth, Fort Worth, United States
Memorial Hermann, Houston, United States
University of Texas MD Anderson Cancer Center, Houston, United States
Texas Oncology - San Antonio Medical Center, San Antonio, United States
Texas Oncology - The Woodlands, Gynecologic Oncology, The Woodlands, United States
Huntsman Cancer Institute, Salt Lake City, United States
Virginia Oncology Associates, Norfolk, United States
Froedtert and Medical College of Wisconsin, Milwaukee, United States
Newcastle Private Hospital, New Lambton Heights, Australia
Northern Cancer Institute St Leonards, Saint Leonards, Australia
Prince of Wales Hospital, Sydney, Australia
Westmead Hospital, Westmead, Australia
Royal Brisbane and Women's Hospital, Brisbane, Australia
Brian Fricker Oncology Centre, Burnside Hospital, Toorak Gardens, Australia
Peter MacCallum Cancer Center, Melbourne, Australia
St John of God Subiaco Hospital, Subiaco, Australia
UZ Leven, Leuven, Belgium
Alberta Health Services - University of Calgary, Calgary, Canada
Alberta Health Services and The University of Alberta, Edmonton, Canada
BC Cancer - Abbotsford, Abbotsford British Columbia, Canada
BC Cancer - Kelowna, Kelowna, Canada
BC Cancer - Surrey, Surrey, Canada
CancerCare Manitoba, Winnipeg, Canada
Nsha-Qeii Hsc, Halifax, Canada
Juravinski Cancer Center, Hamilton, Canada
London Health Sciences Center, London, Canada
Ottawa Hospital Cancer Centre, Ottawa, Canada
Centre Hospitalier de l'Université de Montreal, Montreal, Canada
McGill University Health Center, Montreal, Canada
Centre Integre Universitaire de sante et de service sociaux de l'Estri-Centre hospitalier univeritaire de Sherbrooke, Sherbrooke, Canada
Masaryk Memorial Cancer Institute, Brno, Czechia
Department of Gynecology and Obstetrics, Oncogynecological center U hiversity Hospital Kralovske Vinohrady, Prague, Czechia
KOC KNTB a.s. Zlfn, Hvalfckovo nabrezf 600, 76001, Zlín, Czechia
Aalborg University Hospital, Aalborg, Denmark
Odense University Hospital, Odense, Denmark
Kuopio University Hospital, Kuopio, Finland
Klinik für Frauenheilkunde und Geburtshilfe, Dessau, Germany
Universitaetsklinikum Duesseldorf / Klinik fur Frauenheilkunde & Geburtshilfe, Düsseldorf, Germany
Universitatsklinikum National Centrum for Tumor Disease (NCT), Heidelberg, Germany
Universitätslinikum Mannheim, Frauenklinik, Mannheim, Germany
Kliniken Suedostbayern AG, Klinikum Traunstein, Traunstein, Germany
Attikon General University Hospital, Chaïdári, Greece
University Hospital Attikon, Chaïdári, Greece
Alexandra Hospital, Athens, Greece
General Hospital of Patras, Pátrai, Greece
Euromedica General Clinic, B' Oncology Clinic, Thessaloniki, Greece
Cork University Hospital, Cork, Ireland
Bon Secours Hospital, Cork, Ireland
University Hospital Limerick, Limerick, Ireland
University Hospital Waterford, Waterford, Ireland
Shaare Zedek Medical Oncology, Jerusalem, Israel
Meir Medical Center, Kfar Saba, Israel
Galilee Medical Center, Nahariya, Israel
Sheba Medical Center, Ramat Gan, Israel
Ziv Medical Center, Safed, Israel
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Centro di Riferimento Oncologico, CRO-IRCCS, Aviano, Italy
Candiolo Cancer Institute - IRCCS, Candiolo, Italy
Arnas Garibaldi, Catania, Italy
University G, D'Annunuzio-Chieti, Chieti, Italy
IRCCS Instituto Nazionale Tumori, Naples, Italy
Azienda Ospedaliera Universitaria Policlinico Umberto I, Roma, Italy
Policlinico Agostino Gemelli, Roma, Italy
Ospedale S. Giovanni Calibita Fatebenefratelli, Roma, Italy
Ospedale San Bortolo, Vicenza, Italy
University of Tsukuba Hospital, Tsukuba, Japan
National Cancer Center Hospital East, Kashiwa, Japan
Kurume University Hospital, Kurume, Japan
Yokohama City University Hospital, Yokohama, Japan
Gunma University Hospital, Maebashi, Japan
Gunma Prefectural Cancer Center, Ota-shi, Japan
Hiroshima City Hiroshima Citizens Hospital, Naka, Japan
Hyogo Cancer Center, Akashi, Japan
Iwate Medical University, Morioka, Japan
Nippon Medical School Musashikosugi Hospital, Kawasaki-shi, Japan
Kanagawa Cancer Center, Yokohama, Japan
National Defense Medical College Hospital, Tokorozawa, Japan
Osaka International Cancer Institute, Chuo, Japan
Kindai University Hospital, Ōsaka-sayama, Japan
Saitama Medical University International Medical Center, Hidaka, Japan
Keio University Hospital, Shinjuku-Ku, Japan
The Cancer Institute Hospital of JFCR, Koto-Ku, Japan
Saitama Cancer Center, Saitama, Japan
Kagawa Prefectural Central Hospital, Takamatsu, Japan
National Cancer Center Hospital, Tokyo, Japan
Auckland City Hospital, Auckland, New Zealand
Christchurch Hospital, Christchurch, New Zealand
Waikato Hospital, Hamilton, New Zealand
Palmerston North Hospital, Palmerston North, New Zealand
Tauranga Hospital, Tauranga, New Zealand
Chair & department of Obsterics, Gynaecology and Oncology (previous site), Warsaw, Poland
Bialostockie Centrum Onkologii Oddzial Onkologii Ginekologicznej, Bialystok, Poland
University Hospital of Bialystok, Bialystok, Poland
Szpitale Pomorskie sp zoo, Gdynia, Poland
Medical University of Lublin, Lublin, Poland
Wielkopolskie Centrum Onkologii, Poznan, Poland
Pomeranian Medical University, Szczecin, Poland
Spitalul Clinic Municipal "Dr. Gavril Curteanu", Oradea, Romania
S.C. Medisprof S.R.L., Cluj-Napoca, Romania
Oncopremium Team, Baia Mare, Romania
SC Quantum Medical Center SRL, Bucharest, Romania
Instiute of Oncology - Medical Oncology, Cluj-Napoca, Romania
Centrul de Oncologie Sf.Nectarie, Craiova, Romania
S.C Oncolab S.R.L, Craiova, Romania
Institutul Regional de Oncologie Iasi, Iași, Romania
Spital Municipal Ploiesti, Ploieşti, Romania
Spitalul Judetean de Urgenta "Sfantul Ioan cel Nou" Suceava, Suceava, Romania
ONCOMED Timisoara, Timișoara, Romania
Arkhangelsk Clinical Oncological Dispensary, Arkhangelsk, Russia
BHI of Omsk Region Clinical Oncology Dispensary, Omsk, Russia
Orenburg Regional Clinical Oncological Dispensary, Orenburg, Russia
SBHI Saint Petersburg Research Center specialized types of medical care (Oncology), Pesochnyy, Russia
SBHI SR Pyatigorsk Interdistrict Oncology Dispensary, Pyatigorsk, Russia
Limited Liability Company MedPomosch, Saint Petersburg, Russia
FSBEI HE I.P. Pavlov SPbSMU MoH Russia, Saint Petersburg, Russia
Saint-Petersburg State Budget Institution of Healthcare City Clinical Oncology Dispensary, Saint Petersburg, Russia
1st Medical University, Saint Petersburg, Russia
Federa; State Budgetary Educational Institution of Higher Education National Research Ogarev Mordovia State University, Saransk, Russia
State Medical Institution "Oncology Center #2" under the Krasnodar Region Healthcare Department, Sochi, Russia
National University Hospital, Singapore, Singapore
National Cancer Center Singapore, Singapore, Singapore
National Cancer Center, Goyang-si, South Korea
CHA Bundang Medical Center, Seongnam-si, South Korea
Seoul National University Bundang Hospital, Seongnam-si, South Korea
Gachon University Gil Medical Center, Incheon, South Korea
SoonChunHyang University Cheonan Hospital, Cheonan, South Korea
Korea Cancer Center Hospital, Seoul, South Korea
Seoul National University Hospital, Seoul, South Korea
Severance Hospital, Yonsei University Health System, Seoul, South Korea
Konkuk University Medical Center, Seoul, South Korea
Asan Medical Center, Seoul, South Korea
Samsung Medical Center, Seoul, South Korea
Korea University Guro Hospital, Seoul, South Korea
Ajou University Hospital, Suwon, South Korea
Vall d'Hebron Institute of Oncology, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Hospital Universitario Basurto, Bilbao, Spain
Consorcio Hospitalario Provincial Castellon, Castillón, Spain
Hospital Virgen de la Arrixaca, El Palmar, Spain
Hospital de Jerez, Jerez de la Frontera, Spain
Hospital Universitario Puerta de Hierro - Majadahonda, Madrid, Spain
Hospital Universitario Central de Asturias, Oviedo, Spain
Hospital Son Llatzer, Palma de Mallorca, Spain
Hospital Nuestra Señora de Valme, Seville, Spain
Onkologiska Kliniken, Linköping, Sweden
Onkologiska Kliniken, Lund, Sweden
Karolinska Universitetssjukhuset, Stockholm, Sweden
Hualien Tzu Chi Hospital, Hualien City, Taiwan
Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan
Far Eastern Memorial Hospital, New Taipei City, Taiwan
Taichung Veterans General Hospital, Taichung, Taiwan
China Medical University Hospital, Taichung, Taiwan
Chi Mei Hospital, Liouying (CMHLY), Tainan, Taiwan
Chi Mei Medical Center (CMMC), Tainan, Taiwan
National Taiwan University Hospital, Taipei, Taiwan
Mackay Memorial Hospital, Taipei, Taiwan
Taipei Veterans General Hospital, Taipei, Taiwan
Tri-Service General Hospital, Taipei, Taiwan
Taipei Medical University Hospital, Taipei, Taiwan
Chang Gung Medical Foundation- Linkou Branch, Taoyuan District, Taiwan
Dr. Abdurrahman Yurtaslan Ankara Women's Health Education and Research Hospital, Ankara, Turkey (Türkiye)
Istanbul University-cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey (Türkiye)
Koc University School of Medicine, Koc University Hospital, Istanbul, Turkey (Türkiye)
Celal Bayar University Faculty of Medicine, Manisa, Turkey (Türkiye)
Baskent University Hospital, Yüreğir, Turkey (Türkiye)
East Kent Hospitals University NHS Foundation trust Medical Oncology, Canterbury, United Kingdom
Northampton General Hospital, Cliftonville, United Kingdom
Royal Sussex County Hospital, Brighton, United Kingdom
Bristol Cancer Institute Medical Oncology, Bristol, United Kingdom
Addenbrookes Hospital, Cambridge, United Kingdom
Western General Hospital, Edinburgh, United Kingdom
University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, United Kingdom
St. James University Hospital, Leeds, United Kingdom
Barts and the London NHS Trust, London, United Kingdom
University of College London Hospital, London, United Kingdom
Guy's & St Thomas' NHS Foundation Trust (Guy's Cancer Centre), London, United Kingdom
The Royal Marsden NHS Foundation Trust, London, United Kingdom
Imperial College London, London, United Kingdom
The James Cook University Hospital, Middlesbrough, United Kingdom
Poole Hospital NHS Foundation Trust, Poole, United Kingdom
South West Wales Cancer Centre - Singleton Hospital, Swansea, United Kingdom
Musgrove Park Hospital, Taunton, United Kingdom