Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3)
- Conditions
- Fallopian Tube CancerOvarian CancerPeritoneal Cancer
- Interventions
- Drug: PlaceboDrug: Rucaparib
- Registration Number
- NCT01968213
- Lead Sponsor
- pharmaand GmbH
- Brief Summary
Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.
- Detailed Description
Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). Clinical data have shown that ovarian cancer patients with and without evidence of a gBRCA mutation benefit from treatment with a PARP and that maintenance treatment with a PARP inhibitor following a response to platinum-based treatment increases PFS in patients with ovarian cancer. While patients with a BRCA mutation derived the most benefit, patients without evidence of a BRCA mutation also derived significant benefit.
Patients enrolled into this study will be stratified into 3 groups based on tumor HRD status. The purpose of this study is to identify which of these groups of patients will most likely benefit from treatment with rucaparib. It is anticipated that rucaparib will provide therapeutic benefit and increase PFS in patients with HRD associated with a BRCA gene mutation or other HR gene alteration.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 564
- Confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer.
- Received ≥2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial.
- Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen.
- Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response.
- For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response.
- Have sufficient archival tumor tissue for analysis.
- History of prior cancer except for non-melanoma skin cancer, breast cancer curatively > 3 years ago, curatively treated solid tumor (>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer.
- Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible.
- Untreated or symptomatic central nervous system metastases.
- Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drug.
- Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole. Rucaparib Rucaparib Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
- Primary Outcome Measures
Name Time Method Disease Progression According to RECIST Version 1.1, as Assessed by the Investigator, or Death From Any Cause (Investigator Progression Free Survival as Per invPFS) Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 3 years. Progression-free survival by Investigator (invPFS) is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever occurs first. Progressive disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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).
- Secondary Outcome Measures
Name Time Method Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS) Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 8.2 years. To evaluate PFS by RECIST v1.1, as assessed by independent radiology review (IRR).
Overall Survival (OS) All patients were followed for survival up to approximately 8.2 years. Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive.
Time to an 8-point Decrease in the Total Score of the FOSI-18 Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years. The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related physical, emotional and treatment-related symptoms, and is based on numerical point scoring of symptoms. The questionnaire is designed to evaluate changes in the total score in individual assessments over time. This study looked at the time to an 8-point reduction in the total score as an indicator of improvement in disease-related symptoms on cancer therapy.
Individual Model Parameter Estimates of Rucaparib and Covariates Identification Study data collection occurred over approximately 7 months. Concentration summary statistics
Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18 Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years. The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related symptoms and is based on numerical point scoring of symptoms. The DRS-P subscale of the questionnaire is specifically designed to assess physical symptoms of ovarian cancer and evaluate changes in the subscale point score in individual assessments over time. This study looked at the time to a 4-point reduction in subscale score as an indicator of improvement in disease-related physical symptoms on cancer therapy.
Trial Locations
- Locations (96)
Saint Jude Heritage Medical Center
🇺🇸Fullerton, California, United States
University of California Los Angeles (UCLA)
🇺🇸Santa Monica, California, United States
Johns Hopkins Universty
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Hope Women's Cancer Centers
🇺🇸Asheville, North Carolina, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hospital Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
St John of God Hospital Subiaco
🇦🇺Subiaco, Western Australia, Australia
UZ Gent
🇧🇪Gent, Belgium
CHUM Centre Hospitalier de l'Université de Montréal
🇨🇦Montreal, Quebec, Canada
Royal Marsden Hospital
🇬🇧London, England, United Kingdom
Oncology Institute, Sheba Medical Center
🇮🇱Ramat Gan, Israel
Assaf Harofeh M.C.
🇮🇱Zerifin, Israel
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
Belfast City Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
University of Washington at Seattle
🇺🇸Seattle, Washington, United States
Clinique Sainte-Elisabeth
🇧🇪Namur, Belgium
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Arcispedale Santa Maria Nuova IRCCS
🇮🇹Reggio Emilia, Reggio Nella Emilia, Italy
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie
🇩🇪Wiesbaden, Hessen, Germany
UZ Leuven
🇧🇪Leuven, Belgium
Hospital Tenon
🇫🇷Paris, France
Institut Gustave Roussy
🇫🇷Villejuif, Ile De France, France
Institut Claudius Regaud
🇫🇷Toulouse, Midi-Pyrenees, France
Institute Bergonie
🇫🇷Bordeaux, France
Rotkreuzklinikum Muenchen gGmbH
🇩🇪Munich, Bavaria, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt am Main, Hessen, Germany
AZ St Augustinus
🇧🇪Antwerpen, Belgium
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Centre Francois Baclesse
🇫🇷Caen Cedex 05, Basse-Normandie, France
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Azienda Ospedaliero Universitaria Policlinico di Modena
🇮🇹Modena, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale
🇮🇹Napoli, Italy
Oncology Unit City Hospital degli Infermi
🇮🇹Faenza, Ravenna, Italy
Centre Hospitalier Universitaire de Québec
🇨🇦Quebec, Canada
Auckland City Hospital
🇳🇿Auckland, Grafton, New Zealand
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
🇪🇸Madrid, Spain
Klinikum Stuttgart
🇩🇪Stuttgart, Baden-Wuerttemberg, Germany
Hospital Regional Universitario Carlos Haya de Malaga
🇪🇸Malaga, Spain
Barts Health NHS Trust
🇬🇧London, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, Surrey, United Kingdom
Sarah Cannon Reserach Institute UK
🇬🇧London, United Kingdom
University College London
🇬🇧London, United Kingdom
Centre Leon Berard
🇫🇷Lyon, Rhone-Alpes, France
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom
Klinikum Ludwigsburg-Bietigheim gGmbH
🇩🇪Ludwigsburg, Baden-Wuerttembert, Germany
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
🇮🇹Bologna, Italy
Rambam Health Care Campus
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petach-Tikva, Israel
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Centro Oncologico de Galica
🇪🇸A Coruna, Spain
Palmsteron North Hospital
🇳🇿Palmerston North, Manawatu, New Zealand
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Hospital Vall D'Hebron
🇪🇸Barcelona, Spain
St. James University Hospital
🇬🇧Leeds, West Yorkshire, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Instituto Europeo di Oncologia
🇮🇹Milan, Italy
Hôpital Européen Georges-Pompidou
🇫🇷Paris, Ile-de-France, France
Centre Catherine de Sienne
🇫🇷Nantes Cedex, Pays De La Loire, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, Rhone-Alpes, France
London Regional Cancer Centre
🇨🇦London, Ontario, Canada
Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Hospital Universitario San Carlos
🇪🇸Madrid, Spain
Instituto Valencia de Oncologia-Fundacion
🇪🇸Valencia, Spain
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Sachsen, Germany
Technische Universität Dresden
🇩🇪Dresden, Sachsen, Germany
Rocky Mountain Cancer Centers
🇺🇸Lakewood, Colorado, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Coastal Integrative Cancer Care
🇺🇸San Luis Obispo, California, United States
Central Coast Medical Oncology
🇺🇸Santa Maria, California, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine - Division of Gynaecological Oncology
🇺🇸Saint Louis, Missouri, United States
Prince of Wales Hospital
🇦🇺Sydney, New South Wales, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Fondazione IRCCS National Cancer Institute
🇮🇹Milan, Italy
Wellington Hospital
🇳🇿Newtown, Wellington, New Zealand
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Sir Bobby Robson Cancer trials research Centre, Northern Centre For Cancer Care
🇬🇧Newcastle Upon Tyne, United Kingdom
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
University of California San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Karmanos Cancer Institute - Wayne State University
🇺🇸Detroit, Michigan, United States
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