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

NCT02855944 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CO-338-0432016-000816-14
• Study Type: interventional
• Target: 349
• Locations: 12 countries
• Sites: 77

Brief Summary

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.

Conditions

Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

ovarian cancer; fallopian tube cancer; primary peritoneal cancer; peritoneal cancer; platinum sensitive; relapsed disease; PARP Inhibitor; PARP; rucaparib; ruca; homologous recombination; homologous recombination deficiency; genomic scarring; loss of heterozygosity; CO-338; PF-01367338; PF 01367338; CO-338-043; platinum sensitive ovarian cancer; platinum sensitive fallopian tube cancer; platinum sensitive primary peritoneal cancer; platinum sensitive peritoneal cancer; gynecological cancer; Clovis; Clovis oncology; ARIEL2; ARIEL 2; ARIEL-2; ARIEL-3; ARIEL 3; ARIEL3; ARIEL4; ARIEL-4; ARIEL 4; A4; advanced OC; platinum resistant ovarian cancer; platinum resistant primary ovarian cancer; Rubraca; High grade serous; Partially platinum sensitive

Outcome Measures

Primary Outcomes (2)

• Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)

  The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

• Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)

  The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Secondary Outcomes (10)

• Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)

  Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

• Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)

  Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

• Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)

  Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

• Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)

  Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

• Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)

  Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Study Arms (2)

Rucaparib

EXPERIMENTAL

Drug: Oral rucaparib 600 mg BID (twice a day) Other Names: * CO-338 * PF 01367338 * AG 14699 * Rubraca

Drug: Rucaparib

Chemotherapy

ACTIVE COMPARATOR

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.

Drug: Chemotherapy

Interventions

Chemotherapy DRUG

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

Also known as: Cisplatin, carboplatin, carboplatin/paclitaxel, carboplatin/gemcitabine, paclitaxel

Chemotherapy

Rucaparib DRUG

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

Also known as: CO-338, AG 14699, PF 01367338, Rubraca

Rucaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• pharmaand GmbH: lead
• Foundation Medicine: collaborator

Study Sites (77)

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Hospital Haroldo Juacaba Instituto do Cancer do Ceara

Fortaleza, Ceará, Brazil

Location

Instituto de Oncologia do Parana (IOP)

Curitiba, Paraná, Brazil

Location

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

Porto Alegre, Rio Grande do Sul, Brazil

Location

CEPON-Centro de pesquisas Oncologicas

Florianópolis, Santa Catarina, Brazil

Location

Hospital do Cancer de Barretos

Barretos, São Paulo, Brazil

Location

Instituto Nacional de Câncer Hospital do Câncer II

Rio de Janeiro, Brazil

Location

Hospital Pérola Byington - Centro de Referência da Saúde da Mulher

São Paulo, Brazil

Location

Hospital São Camilo

São Paulo, Brazil

Location

Tom Baker Cancer Center

Calgary, Alberta, Canada

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

Centre Hospitalier de L'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Location

CIUSSS de l'Estrie CHUS

Sherbrooke, Quebec, Canada

Location

Masarykuv Onkologicky Ustav, Oddeleni komplexni klinicke onkologie

Brno, Jihormoravsky KRAJ, Czechia

Location

Fakultni Nemocnice v Motole

Prague, Prague, Czechia

Location

Fakultní Nemocnice Ostrava

Ostrava, Czechia

Location

Všeobecná Fakultní Nemocnice v Praze

Prague, Czechia

Location

Debreceni Egyetem Klinikai Központ

Debrecen, Hajdú-Bihar, Hungary

Location

Országos Onkológiai Intézet

Budapest, Hungary

Location

Carmel Medical Center

Haifa, Israel

Location

Edith Wolfson Medical Center

Holon, Israel

Location

Hadassah Medical Organization

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center, Oncology Dept.

Tel Aviv, Israel

Location

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

Bologna, Italy

Location

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

Candiolo, Italy

Location

AO per l'emergenza Cannizzaro

Catania, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico di Modena

Modena, Italy

Location

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

Napoli, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

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

Grzybnica, West Pomeranian Voivodeship, Poland

Location

Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie

Bialystok, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, Poland

Location

Wojewodzki Szpital Specjalistyczny w Olsztynie

Olsztyn, Poland

Location

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

Poznan, Poland

Location

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

Szczecin, Poland

Location

Arkhangelsk Clinical Oncological Dispensary

Arkhangelsk, Russia

Location

Kursk Regional Oncologic Dispensary

Kursk, Russia

Location

Moscow Clinical Scientific and Practical Center of Moscow Healthcare Department

Moscow, 115478, Russia

Location

Omsk Region Clinical Oncologic Dispensary

Omsk, Russia

Location

Pyatigorsk Oncological Dispensary

Pyatigorsk, Russia

Location

Ryazan Regional Clinical Oncology Dispensary

Ryazan, Russia

Location

Pavlov First Saint-Petersburg State Medical University

Saint Petersburg, Russia

Location

Saint Petersburg City Oncological Dispensary

Saint Petersburg, Russia

Location

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

Saint Petersburg, Russia

Location

Republican oncological dispensary of Republic of Mordovia

Saransk, Russia

Location

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

Sochi, Russia

Location

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

Ufa, Russia

Location

Centro Oncologico Regional de Galicia

A Coruña, Spain

Location

Hospital Duran i Reynals

Barcelona, Spain

Location

Hospital Universitari Vall DHebron

Barcelona, Spain

Location

Hospital Universitari de Girona Doctor Josep Trueta

Girona, Spain

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

MD Anderson Cancer Center

Madrid, Spain

Location

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

Madrid, Spain

Location

Dnipropetrovsk City Multifield Clinical Hospital Number 4

Dnipropetrovsk, Ukraine

Location

National Cancer Institute of the Ministry of Health of Ukraine

Kyiv, Ukraine

Location

Volyn Regional Oncology Dispensary

Lutsk, Ukraine

Location

Lviv Regional Oncology Dispensary

Lviv, Ukraine

Location

Sumy Regional Oncology Center

Sumy, Ukraine

Location

Zakarpattya Regional Clinical Oncological Dispensary

Uzhhorod, Ukraine

Location

The Christie NHS Foundation Trust - Clinical Trial Pharmacy

Manchester, England, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom

Location

Velindre NHS Trust

Cardiff, United Kingdom

Location

University Hospital of Coventry and Warwickshire NHS Trust

Coventry, United Kingdom

Location

Derby Teaching Hospital NHS Foundation Trust

Derby, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, United Kingdom

Location

University College London Hospitals

London, United Kingdom

Location

East and North Hertfordshire NHS Trust

Middlesex, United Kingdom

Location

Newcastle Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 39914419 DERIVED

• 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.

  PMID: 35298906 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Recurrence

Interventions

Drug Therapy; Cisplatin; Carboplatin; CP protocol; Gemcitabine; Paclitaxel; rucaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Fallopian Tube Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Information Department
• Organization: Clovis Oncology, Inc.

medinfo@clovisoncology.com

+1 415 409 7220

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2016
• First Posted: August 4, 2016
• Study Start: March 1, 2017
• Primary Completion: December 3, 2020
• Study Completion: September 16, 2022
• Last Updated: June 9, 2023
• Results First Posted: February 11, 2022

Record last verified: 2023-06

Locations

CA (5); CZ (4); UA (6); US (2); IL (6); IT (8); BR (8); RU (12); PL (6); HU (2); ES (8); GB (10)