Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3)
ARIEL3
A Study of Rucaparib as Switch Maintenance Following Platinum-Based Chemotherapy in Patients With Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer ( ARIEL3 )
2 other identifiers
interventional
564
11 countries
96
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 ovarian-cancer
Started Apr 2014
Longer than P75 for phase_3 ovarian-cancer
96 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 17, 2013
CompletedFirst Posted
Study publicly available on registry
October 23, 2013
CompletedStudy Start
First participant enrolled
April 7, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2017
CompletedResults Posted
Study results publicly available
August 3, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 7, 2022
CompletedJune 9, 2023
June 1, 2023
3 years
October 17, 2013
May 8, 2018
June 7, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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)
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).
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.
Secondary Outcomes (5)
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.
Overall Survival (OS)
All patients were followed for survival up to approximately 8.2 years.
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.
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.
Individual Model Parameter Estimates of Rucaparib and Covariates Identification
Study data collection occurred over approximately 7 months.
Study Arms (2)
Rucaparib
EXPERIMENTALOral 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.
Placebo
PLACEBO COMPARATOROral 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.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- pharmaand GmbHlead
- Foundation Medicinecollaborator
- Myriad Genetics, Inc.collaborator
Study Sites (96)
University of Arizona Cancer Center
Tucson, Arizona, 85704, United States
Saint Jude Heritage Medical Center
Fullerton, California, 92835, United States
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
University of California San Francisco (UCSF)
San Francisco, California, 94158, United States
Coastal Integrative Cancer Care
San Luis Obispo, California, 93422, United States
Central Coast Medical Oncology
Santa Maria, California, 93454, United States
University of California Los Angeles (UCLA)
Santa Monica, California, 90404, United States
Rocky Mountain Cancer Centers
Lakewood, Colorado, 80228, United States
Memorial Healthcare System
Hollywood, Florida, 33021, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Florida Hospital
Orlando, Florida, 32804, United States
Johns Hopkins Universty
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Karmanos Cancer Institute - Wayne State University
Detroit, Michigan, 48201, United States
Washington University School of Medicine - Division of Gynaecological Oncology
St Louis, Missouri, 63110, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Hope Women's Cancer Centers
Asheville, North Carolina, 28806, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Washington at Seattle
Seattle, Washington, 98109, United States
Prince of Wales Hospital
Sydney, New South Wales, 2031, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Royal Brisbane & Women's Hospital
Herston, Queensland, 4029, Australia
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3052, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
St John of God Hospital Subiaco
Subiaco, Western Australia, 608, Australia
AZ St Augustinus
Antwerp, 2610, Belgium
UZ Gent
Ghent, B-9000, Belgium
UZ Leuven
Leuven, 3000, Belgium
Clinique Sainte-Elisabeth
Namur, 5000, Belgium
Tom Baker Cancer Centre
Calgary, Alberta, T2N4N2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G1Z2, Canada
Juravinski Cancer Centre
Hamilton, Ontario, L8V5C2, Canada
London Regional Cancer Centre
London, Ontario, N6A4L6, Canada
Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H8L6, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G2M9, Canada
CHUM Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2L4M1, Canada
Centre Hospitalier Universitaire de Québec
Québec, G1R2J6, Canada
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69373, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France
Centre Francois Baclesse
Caen, Basse-Normandie, 14076, France
Institut Claudius Regaud
Toulouse, Midi-Pyrenees, 31052, France
Centre Catherine de Sienne
Nantes, Pays de la Loire Region, 44202, France
Institute Bergonie
Bordeaux, 33076, France
Hospital Tenon
Paris, 75020, France
Hôpital Européen Georges-Pompidou
Paris, Île-de-France Region, 75908, France
Institut Gustave Roussy
Villejuif, Île-de-France Region, 94805, France
Klinikum Ludwigsburg-Bietigheim gGmbH
Ludwigsburg, Baden-Wuerttembert, 71640, Germany
Klinikum Stuttgart
Stuttgart, Baden-Wurttemberg, 70174, Germany
Rotkreuzklinikum Muenchen gGmbH
Munich, Bavaria, 80637, Germany
Universitätsklinikum Frankfurt
Frankfurt am Main, Hesse, 60596, Germany
Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie
Wiesbaden, Hesse, 65199, Germany
Klinikum Chemnitz gGmbH
Chemnitz, Saxony, 09116, Germany
Technische Universität Dresden
Dresden, Saxony, 01307, Germany
Rambam Health Care Campus
Haifa, 31096, Israel
Lady Davis Carmel Medical Center
Haifa, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
Oncology Institute, Sheba Medical Center
Ramat Gan, 52621, Israel
Sourasky Medical Center
Tel Aviv, 64239, Israel
Assaf Harofeh M.C.
Ẕerifin, 70300, Israel
Oncology Unit City Hospital degli Infermi
Faenza, Ravenna, 48018, Italy
Arcispedale Santa Maria Nuova IRCCS
Reggio Emilia, Reggio Nella Emilia, 42100, Italy
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
Bologna, 40138, Italy
Fondazione IRCCS National Cancer Institute
Milan, 20133, Italy
Instituto Europeo di Oncologia
Milan, 20141, Italy
Azienda Ospedaliero Universitaria Policlinico di Modena
Modena, 41124, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Napoli, 80131, Italy
Policlinico Universitario Agostino Gemelli
Roma, 00158, Italy
Auckland City Hospital
Auckland, Grafton, 1023, New Zealand
Palmsteron North Hospital
Palmerston North, Manawatu, 4442, New Zealand
Wellington Hospital
Newtown, Wellington Region, 6021, New Zealand
Hospital Central de Asturias
Oviedo, Principality of Asturias, 33011, Spain
Centro Oncologico de Galica
A Coruña, 15009, Spain
Hospital Vall D'Hebron
Barcelona, 8035, Spain
Hospital Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario San Carlos
Madrid, 28040, Spain
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
Madrid, 28050, Spain
Hospital Regional Universitario Carlos Haya de Malaga
Málaga, 29011, Spain
Hospital Universitario Virgen del Rocío
Seville, 41013, Spain
Instituto Valencia de Oncologia-Fundacion
Valencia, 46009, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Royal Marsden Hospital
London, England, SW3 6JJ, United Kingdom
Belfast City Hospital
Belfast, Northern Ireland, BT9 7AB, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, G120YN, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT, United Kingdom
St. James University Hospital
Leeds, West Yorkshire, LS97TF, United Kingdom
Addenbrookes Hospital
Cambridge, CB20QQ, United Kingdom
Barts Health NHS Trust
London, EC1M6BQ, United Kingdom
Imperial College Healthcare NHS Trust
London, W120HS, United Kingdom
Sarah Cannon Reserach Institute UK
London, W1G6AD, United Kingdom
University College London
London, W1T4TJ, United Kingdom
The Christie NHS Foundation Trust
Manchester, M204BX, United Kingdom
Sir Bobby Robson Cancer trials research Centre, Northern Centre For Cancer Care
Newcastle upon Tyne, NE77DN, United Kingdom
Related Publications (6)
Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. doi: 10.1016/j.ygyno.2023.05.060. Epub 2023 May 30.
PMID: 37262961DERIVEDGreen ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
PMID: 35397664DERIVEDTattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
PMID: 35170751DERIVEDColombo N, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Meunier J, Cameron T, Maloney L, Goble S, Bedel J, Ledermann JA, Coleman RL. The effect of age on efficacy, safety and patient-centered outcomes with rucaparib: A post hoc exploratory analysis of ARIEL3, a phase 3, randomized, maintenance study in patients with recurrent ovarian carcinoma. Gynecol Oncol. 2020 Oct;159(1):101-111. doi: 10.1016/j.ygyno.2020.05.045. Epub 2020 Aug 26.
PMID: 32861537DERIVEDLedermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. doi: 10.1016/S1470-2045(20)30061-9.
PMID: 32359490DERIVEDColeman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12.
PMID: 28916367DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Information Department
- Organization
- Clovis Oncology, Inc.
Study Officials
- STUDY DIRECTOR
Heidi Giordano
Clovis Oncology, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 17, 2013
First Posted
October 23, 2013
Study Start
April 7, 2014
Primary Completion
April 1, 2017
Study Completion
July 7, 2022
Last Updated
June 9, 2023
Results First Posted
August 3, 2018
Record last verified: 2023-06