Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3)

NCT ID: NCT01968213

Last Updated: 2023-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 564 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-07
• Study Completion Date: 2022-07-07

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Rucaparib

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

CO-338; PF 01367338; AG 14699

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Foundation Medicine

INDUSTRY

Sponsor Role: collaborator

Myriad Genetics, Inc.

INDUSTRY

Sponsor Role: collaborator

pharmaand GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heidi Giordano

Role: STUDY_DIRECTOR

Clovis Oncology, Inc.

Locations

University of Arizona Cancer Center

Tucson, Arizona, United States

Saint Jude Heritage Medical Center

Fullerton, California, United States

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

University of California San Francisco (UCSF)

San Francisco, California, United States

Coastal Integrative Cancer Care

San Luis Obispo, California, United States

Central Coast Medical Oncology

Santa Maria, California, United States

University of California Los Angeles (UCLA)

Santa Monica, California, United States

Rocky Mountain Cancer Centers

Lakewood, Colorado, United States

Memorial Healthcare System

Hollywood, Florida, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Florida Hospital

Orlando, Florida, United States

Johns Hopkins Universty

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Karmanos Cancer Institute - Wayne State University

Detroit, Michigan, United States

Washington University School of Medicine - Division of Gynaecological Oncology

St Louis, Missouri, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, 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

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Washington at Seattle

Seattle, Washington, United States

Prince of Wales Hospital

Sydney, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

St John of God Hospital Subiaco

Subiaco, Western Australia, Australia

AZ St Augustinus

Antwerp, , Belgium

UZ Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Clinique Sainte-Elisabeth

Namur, , Belgium

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

London Regional Cancer Centre

London, Ontario, Canada

Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

CHUM Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Québec

Québec, , Canada

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Centre Francois Baclesse

Caen, Basse-Normandie, France

Institut Claudius Regaud

Toulouse, Midi-Pyrenees, France

Centre Catherine de Sienne

Nantes, Pays de la Loire Region, France

Institute Bergonie

Bordeaux, , France

Hospital Tenon

Paris, , France

Hôpital Européen Georges-Pompidou

Paris, Île-de-France Region, France

Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Klinikum Ludwigsburg-Bietigheim gGmbH

Ludwigsburg, Baden-Wuerttembert, Germany

Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, Germany

Rotkreuzklinikum Muenchen gGmbH

Munich, Bavaria, Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, Germany

Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie

Wiesbaden, Hesse, Germany

Klinikum Chemnitz gGmbH

Chemnitz, Saxony, Germany

Technische Universität Dresden

Dresden, Saxony, Germany

Rambam Health Care Campus

Haifa, , Israel

Lady Davis Carmel Medical Center

Haifa, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Oncology Institute, Sheba Medical Center

Ramat Gan, , Israel

Sourasky Medical Center

Tel Aviv, , Israel

Assaf Harofeh M.C.

Ẕerifin, , Israel

Oncology Unit City Hospital degli Infermi

Faenza, Ravenna, Italy

Arcispedale Santa Maria Nuova IRCCS

Reggio Emilia, Reggio Nella Emilia, Italy

Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

Bologna, , Italy

Fondazione IRCCS National Cancer Institute

Milan, , Italy

Instituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliero Universitaria Policlinico di Modena

Modena, , Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Auckland City Hospital

Auckland, Grafton, New Zealand

Palmsteron North Hospital

Palmerston North, Manawatu, New Zealand

Wellington Hospital

Newtown, Wellington Region, New Zealand

Hospital Central de Asturias

Oviedo, Principality of Asturias, Spain

Centro Oncologico de Galica

A Coruña, , Spain

Hospital Vall D'Hebron

Barcelona, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Universitario San Carlos

Madrid, , Spain

Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro

Madrid, , Spain

Hospital Regional Universitario Carlos Haya de Malaga

Málaga, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Instituto Valencia de Oncologia-Fundacion

Valencia, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Royal Marsden Hospital

London, England, United Kingdom

Belfast City Hospital

Belfast, Northern Ireland, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

St. James University Hospital

Leeds, West Yorkshire, United Kingdom

Addenbrookes Hospital

Cambridge, , United Kingdom

Barts Health NHS Trust

London, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

Sarah Cannon Reserach Institute UK

London, , United Kingdom

University College London

London, , United Kingdom

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

Countries

United States; Australia; Belgium; Canada; France; Germany; Israel; Italy; New Zealand; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37262961 (View on PubMed)

Green 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.

Reference Type: DERIVED

PMID: 35397664 (View on PubMed)

Tattersall 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.

Reference Type: DERIVED

PMID: 35170751 (View on PubMed)

Colombo 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.

Reference Type: DERIVED

PMID: 32861537 (View on PubMed)

Ledermann 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.

Reference Type: DERIVED

PMID: 32359490 (View on PubMed)

Coleman 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.

Reference Type: DERIVED

PMID: 28916367 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.arielstudy.com

ARIEL program website

Other Identifiers

2013-000518-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CO-338-014

Identifier Type: -

Identifier Source: org_study_id