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

• ClinicalTrials.gov Identifier: NCT02855944
• Recruitment Status: Recruiting
• First Posted: August 4, 2016
• Last Update Posted: July 2, 2019
• Sponsor: Clovis Oncology, Inc.
• Collaborator: Foundation Medicine
• Information provided by (Responsible Party): Clovis Oncology, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer	Drug: Chemotherapy; Drug: Rucaparib	Phase 3

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). 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 345 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
• Study Start Date: September 2016
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Rucaparib; Drug: Oral rucaparib 600 mg BID Other Names: •CO-338; PF 01367338; AG 14699; Rubraca	Drug: Rucaparib; Tablets of rucaparib, at a dose of 600 mg, will be taken orally twice daily; Other Names: CO-338; AG 14699; PF 01367338; Rubraca
Active Comparator: 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.	Drug: Chemotherapy; Chemotherapy will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.; Other Names: Cisplatin; carboplatin; carboplatin/paclitaxel; carboplatin/gemcitabine; paclitaxel

Outcome Measures

Primary Outcome Measures :

1. Investigator assessed progression-free survival (invPFS) by RECIST Version 1.1 for rucaparib versus chemotherapy [ Time Frame: Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed for the duration of the study, ~4 years ]

Secondary Outcome Measures :

1. Efficacy of rucaparib versus chemotherapy as measured by overall survival (OS) [ Time Frame: study data collection expected to last for ~5 years ]
2. Safety and tolerability of rucaparib versus chemotherapy assessed by AEs reported; clinical laboratory investigations; Vital signs; 12 lead ECGs; Physical examinations; and ECOG performance status [ Time Frame: study data collection expected to last for ~4 years ]
   This is a composite outcome. It will be assessed by Incidence, type, seriousness, and severity of AEs reported; clinical laboratory investigations (hematology and serum chemistry); Vital signs (blood pressure, heart rate, and body temperature); 12 lead ECGs; Physical examinations; and ECOG performance status

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Clovis Oncology Clinical Trial Information; 1-855-262-3040 (USA); clovistrials@emergingmed.com

Contact: Clovis Oncology Clinical Trial Information; +1-303-625-5160 (ex-USA); clovistrials@emergingmed.com

  Hide Study Locations

Locations

United States, Arizona

The University of Arizona Cancer Center; Withdrawn

Tucson, Arizona, United States, 85724

United States, California

University of California Irvine Health Chao Family Comprehensive Cancer Center; Withdrawn

Long Beach, California, United States, 92868

Pacific Cancer Care; Withdrawn

Monterey, California, United States, 93940

University of California San Francisco; Withdrawn

San Francisco, California, United States, 94158

United States, Colorado

Rocky Mountain Cancer Center; Recruiting

Denver, Colorado, United States, 80218

Contact: Heather Harsh 303-385-2000 heather.harsh@usoncology.com

Contact: Katherine Schleich 303-385-2000 katherine.schleich@usoncology.com

Principal Investigator: Ling Ma, MD

United States, Florida

Florida Hospital Cancer Institute; Withdrawn

Orlando, Florida, United States, 32804

United States, Georgia

Augusta University; Recruiting

Augusta, Georgia, United States, 30912

Contact: Donna Wheatley 706-721-8978 dwheatley@augusta.edu

Principal Investigator: Sharad Ghamande, MD

United States, Maine

Maine Medical Center/Maine Medical Partners Women's Health; Withdrawn

Scarborough, Maine, United States, 04074

United States, Michigan

Karmanos Cancer Institute/Wayne State University; Withdrawn

Detroit, Michigan, United States, 48201

United States, New York

Women's Contemporary Care Associates (WCCA) - Mineola; Withdrawn

Mineola, New York, United States

United States, Ohio

University of Cincinnati; Withdrawn

Cincinnati, Ohio, United States

United States, Texas

The University of Texas Health Science Center at Houston; Withdrawn

Houston, Texas, United States

United States, Washington

Seattle Cancer Care Alliance; Withdrawn

Seattle, Washington, United States, 98109

Brazil

Recruiting

Fortaleza, Ceara, Brazil

Recruiting

Curitiba, Parana, Brazil

Recruiting

Ijui, RIO Grande DO SUL, Brazil

Recruiting

Porto Alegre, RIO Grande DO SUL, Brazil

Recruiting

Florianópolis, Santa Catarina, Brazil

Recruiting

Barretos, SAO Paulo, Brazil

Recruiting

Rio de Janeiro, Brazil

Recruiting

Sao Paulo, Brazil

Canada, Alberta

Recruiting

Calgary, Alberta, Canada

Canada, Ontario

Withdrawn

London, Ontario, Canada

Recruiting

Ottawa, Ontario, Canada

Recruiting

Toronto, Ontario, Canada

Canada, Quebec

Recruiting

Montreal, Quebec, Canada

Recruiting

Montréal, Quebec, Canada

Recruiting

Sherbrooke, Quebec, Canada

Czechia

Recruiting

Brno, Jihormoravsky KRAJ, Czechia

Recruiting

Praha 5, Praha, Czechia

Recruiting

Ostrava, Czechia

Recruiting

Praha, Czechia

Hungary

Withdrawn

Miskolc, Borsod-abauj-zemplen, Hungary

Debreceni Egyetem Klinikai Központ; Recruiting

Debrecen, Hajdu-bihar, Hungary

Országos Onkológiai Intézet; Recruiting

Budapest, Hungary

Israel

Recruiting

Haifa, Israel

Recruiting

Holon, Israel

Recruiting

Jerusalem, Israel

Recruiting

Petach-Tikva, Israel

Recruiting

Tel Aviv, Israel

Recruiting

Tel Hashomer, Israel

Italy

Recruiting

Bologna, Italy

Recruiting

Candiolo, Italy

Recruiting

Catania, Italy

Recruiting

Milano, Italy

Recruiting

Modena, Italy

Recruiting

Napoli, Italy

Recruiting

Roma, Italy

Poland

Recruiting

Grzepnica, West Pomeranian Voivodeship, Poland

Recruiting

Bialystok, Poland

Withdrawn

Gdansk, Poland

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie; Recruiting

Lublin, Poland

Recruiting

Olsztyn, Poland

Recruiting

Poznan, Poland

Recruiting

Szczecin, Poland

Russian Federation

Recruiting

Arkhangelsk, Russian Federation

Recruiting

Kursk, Russian Federation

Recruiting

Moscow, Russian Federation

Withdrawn

Nizhny Novgorod, Russian Federation

Recruiting

Omsk, Russian Federation

Recruiting

Pyatigorsk, Russian Federation

Recruiting

Ryazan, Russian Federation

Recruiting

Saint Petersburg, Russian Federation

Recruiting

Saint-Petersburg, Russian Federation

Recruiting

Saransk, Russian Federation

Recruiting

Sochi, Russian Federation

Recruiting

Ufa, Russian Federation

Spain

Recruiting

Barcelona, Spain

Recruiting

Girona, Spain

Recruiting

La Coruna, Spain

Recruiting

Madrid, Spain

Ukraine

Recruiting

Dnipropetrovsk, Ukraine

Recruiting

Kyiv, Ukraine

Recruiting

Lutsk, Ukraine

Recruiting

Lviv, Ukraine

Recruiting

Odessa, Ukraine

Recruiting

Sumy, Ukraine

Recruiting

Uzhgorod, Ukraine

United Kingdom

Recruiting

Manchester, England, United Kingdom

Recruiting

Sutton, Surrey, United Kingdom

Recruiting

Cambridge, United Kingdom

Velindre NHS Trust; Recruiting

Cardiff, United Kingdom

Recruiting

Coventry, United Kingdom

Recruiting

Derby, United Kingdom

Recruiting

Dundee, United Kingdom

Recruiting

Glasgow, United Kingdom

Recruiting

London, United Kingdom

Recruiting

Middlesex, United Kingdom

Recruiting

Newcastle upon Tyne, United Kingdom

Sponsors and Collaborators

Clovis Oncology, Inc.

Foundation Medicine

More Information

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02855944 History of Changes
• Other Study ID Numbers: CO-338-043
• First Posted: August 4, 2016
• Last Update Posted: July 2, 2019
• Last Verified: April 2019

Keywords provided by Clovis Oncology, Inc.:

ARIEL4; ARIEL-4; ARIEL 4; 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

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Fallopian Tube Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Carboplatin; Rucaparib; Antineoplastic Agents, Phytogenic; Antineoplastic Agents