ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

NCT ID: NCT02855944

Last Updated: 2023-06-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

349 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-01

Study Completion Date

2022-09-16

Brief Summary

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The purpose of this study is to determine how patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib versus chemotherapy.

Detailed Description

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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). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies. An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutations.

While PARP inhibitors have demonstrated consistent robust clinical activity in patients with relapsed ovarian cancer associated with HRD, prospective studies evaluating efficacy and safety of PARPi versus standard of care chemotherapy have been limited. The primary purpose of this Phase 3 study is to compare the efficacy and safety of rucaparib versus chemotherapy as treatment for relapsed ovarian cancer in patients with a deleterious BRCA1/2 mutation in their tumor.

Conditions

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Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Rucaparib

Drug: Oral rucaparib

600 mg BID (twice a day)

Other Names:

* CO-338
* PF 01367338
* AG 14699
* Rubraca

Group Type EXPERIMENTAL

Rucaparib

Intervention Type DRUG

Tablets of rucaparib, at a dose of 600 mg, will be taken orally twice a day

Chemotherapy

Monotherapy platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.

Single agent paclitaxel will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.

Group Type ACTIVE_COMPARATOR

Chemotherapy

Intervention Type DRUG

Chemotherapy will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.

Interventions

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Chemotherapy

Chemotherapy will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.

Intervention Type DRUG

Rucaparib

Tablets of rucaparib, at a dose of 600 mg, will be taken orally twice a day

Intervention Type DRUG

Other Intervention Names

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Cisplatin carboplatin carboplatin/paclitaxel carboplatin/gemcitabine paclitaxel CO-338 AG 14699 PF 01367338 Rubraca

Eligibility Criteria

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Inclusion Criteria

* Be 18 years of age at the time the informed consent form is signed
* Have a histologically confirmed diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Received ≥ 2 prior chemotherapy regimens and have relapsed or progressive disease as confirmed by radiologic assessment
* Have biopsiable and evaluable disease. Note: biopsy is optional for patients known to harbor a BRCA1/2 mutation
* Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses

Exclusion Criteria

* History of prior cancers except for those that have been curatively treated, with no evidence of cancer currently (provided all chemotherapy was completed \>6 months prior and/or bone marrow transplant \>2 years prior to first dose of rucaparib).
* Prior treatment with any PARP inhibitor
* Symptomatic and/or untreated central nervous system metastases
* Pre-existing duodenal stent and/or any other gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
* Women who are pregnant or breast feeding
* Hospitalization for bowel obstruction within 3 months prior to enrollment
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Foundation Medicine

INDUSTRY

Sponsor Role collaborator

pharmaand GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Rocky Mountain Cancer Center

Denver, Colorado, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Hospital Haroldo Juacaba Instituto do Cancer do Ceara

Fortaleza, Ceará, Brazil

Site Status

Instituto de Oncologia do Parana (IOP)

Curitiba, Paraná, Brazil

Site Status

União Brasileira de Educação e Assistência / Hospital São Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

CEPON-Centro de pesquisas Oncologicas

Florianópolis, Santa Catarina, Brazil

Site Status

Hospital do Cancer de Barretos

Barretos, São Paulo, Brazil

Site Status

Instituto Nacional de Câncer Hospital do Câncer II

Rio de Janeiro, , Brazil

Site Status

Hospital Pérola Byington - Centro de Referência da Saúde da Mulher

São Paulo, , Brazil

Site Status

Hospital São Camilo

São Paulo, , Brazil

Site Status

Tom Baker Cancer Center

Calgary, Alberta, Canada

Site Status

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Centre Hospitalier de L'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Site Status

CIUSSS de l'Estrie CHUS

Sherbrooke, Quebec, Canada

Site Status

Masarykuv Onkologicky Ustav, Oddeleni komplexni klinicke onkologie

Brno, Jihormoravsky KRAJ, Czechia

Site Status

Fakultni Nemocnice v Motole

Prague, Prague, Czechia

Site Status

Fakultní Nemocnice Ostrava

Ostrava, , Czechia

Site Status

Všeobecná Fakultní Nemocnice v Praze

Prague, , Czechia

Site Status

Debreceni Egyetem Klinikai Központ

Debrecen, Hajdú-Bihar, Hungary

Site Status

Országos Onkológiai Intézet

Budapest, , Hungary

Site Status

Carmel Medical Center

Haifa, , Israel

Site Status

Edith Wolfson Medical Center

Holon, , Israel

Site Status

Hadassah Medical Organization

Jerusalem, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center, Oncology Dept.

Tel Aviv, , Israel

Site Status

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

Bologna, , Italy

Site Status

Istituto per la Ricerca e la Cura del Cancro Istituto di Candiolo

Candiolo, , Italy

Site Status

AO per l'emergenza Cannizzaro

Catania, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Istituto Europeo di Oncologia

Milan, , Italy

Site Status

Azienda Ospedaliero-Universitaria Policlinico di Modena

Modena, , Italy

Site Status

Istituto Nazionale per lo studio e la cura dei tumori "Fondazione Pascale" Oncologia Medica

Napoli, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Site Status

Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna Sp z o.o.

Grzybnica, West Pomeranian Voivodeship, Poland

Site Status

Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie

Bialystok, , Poland

Site Status

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny w Olsztynie

Olsztyn, , Poland

Site Status

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Pozna

Poznan, , Poland

Site Status

Pomorska Akademia Medyczna w Szczecinie, Samodzielny Publiczny Szpital Kliniczny Nr 2

Szczecin, , Poland

Site Status

Arkhangelsk Clinical Oncological Dispensary

Arkhangelsk, , Russia

Site Status

Kursk Regional Oncologic Dispensary

Kursk, , Russia

Site Status

Moscow Clinical Scientific and Practical Center of Moscow Healthcare Department

Moscow, , Russia

Site Status

Omsk Region Clinical Oncologic Dispensary

Omsk, , Russia

Site Status

Pyatigorsk Oncological Dispensary

Pyatigorsk, , Russia

Site Status

Ryazan Regional Clinical Oncology Dispensary

Ryazan, , Russia

Site Status

Pavlov First Saint-Petersburg State Medical University

Saint Petersburg, , Russia

Site Status

Saint Petersburg City Oncological Dispensary

Saint Petersburg, , Russia

Site Status

State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region

Saint Petersburg, , Russia

Site Status

Republican oncological dispensary of Republic of Mordovia

Saransk, , Russia

Site Status

State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region

Sochi, , Russia

Site Status

Republic Clinical Oncology Dispensary of the Ministry of Healthcare of Republic of Bashkortostan

Ufa, , Russia

Site Status

Centro Oncologico Regional de Galicia

A Coruña, , Spain

Site Status

Hospital Duran i Reynals

Barcelona, , Spain

Site Status

Hospital Universitari Vall DHebron

Barcelona, , Spain

Site Status

Hospital Universitari de Girona Doctor Josep Trueta

Girona, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

MD Anderson Cancer Center

Madrid, , Spain

Site Status

Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz

Madrid, , Spain

Site Status

Dnipropetrovsk City Multifield Clinical Hospital Number 4

Dnipropetrovsk, , Ukraine

Site Status

National Cancer Institute of the Ministry of Health of Ukraine

Kyiv, , Ukraine

Site Status

Volyn Regional Oncology Dispensary

Lutsk, , Ukraine

Site Status

Lviv Regional Oncology Dispensary

Lviv, , Ukraine

Site Status

Sumy Regional Oncology Center

Sumy, , Ukraine

Site Status

Zakarpattya Regional Clinical Oncological Dispensary

Uzhhorod, , Ukraine

Site Status

The Christie NHS Foundation Trust - Clinical Trial Pharmacy

Manchester, England, United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

Site Status

Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

Velindre NHS Trust

Cardiff, , United Kingdom

Site Status

University Hospital of Coventry and Warwickshire NHS Trust

Coventry, , United Kingdom

Site Status

Derby Teaching Hospital NHS Foundation Trust

Derby, , United Kingdom

Site Status

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status

University College London Hospitals

London, , United Kingdom

Site Status

East and North Hertfordshire NHS Trust

Middlesex, , United Kingdom

Site Status

Newcastle Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Brazil Canada Czechia Hungary Israel Italy Poland Russia Spain Ukraine United Kingdom

References

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Oza AM, Lisyanskaya A, Fedenko A, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Poka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Kristeleit R. Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Feb;26(2):249-264. doi: 10.1016/S1470-2045(24)00674-0.

Reference Type DERIVED
PMID: 39914419 (View on PubMed)

Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Poka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Oza AM. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Apr;23(4):465-478. doi: 10.1016/S1470-2045(22)00122-X. Epub 2022 Mar 14.

Reference Type DERIVED
PMID: 35298906 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-000816-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CO-338-043

Identifier Type: -

Identifier Source: org_study_id

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