A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

NCT01891344 | Completed Phase 2 Results

• 2 other identifiers: CO-338-0172013-000517-20
• Study Type: interventional
• Target: 491
• Locations: 6 countries
• Sites: 75

Brief Summary

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

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; rucaparib; homologous recombination; homologous recombination deficiency; genomic scarring; loss of heterozygosity; CO-338; PF 01367338; AG 14699; 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; ARIEL3; ARIEL 3

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

  The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator 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 measureable increase in a non-target lesion, or the appearance of new lesions.

  Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

• Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

  The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

  Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Secondary Outcomes (6)

• Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

  Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

• Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

  Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

• Duration of Response Per RECIST v1.1

  Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

• Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

  Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

• Overall Survival (Part 2 of Study)

  All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.

Study Arms (1)

Ovarian cancer

EXPERIMENTAL

rucaparib

Drug: Oral rucaparib

Interventions

Oral rucaparib DRUG

600 mg BID

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

Ovarian cancer

Eligibility Criteria

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

You may qualify if:

• 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 at least 3 prior chemotherapy regimens. Non-chemotherapy regimens and maintenance therapies administered as single agent treatment will not count as a chemotherapy regimen
• Relapsed/progressive disease as confirmed by CT scan
• Have biopsiable and measurable disease. Note: biopsy is optional for patients known to harbor a deleterious gBRCA 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
• Hospitalization for bowel obstruction within 3 months prior to enrollment

Sponsors & Collaborators

• pharmaand GmbH: lead
• Foundation Medicine: collaborator
• Myriad Genetics, Inc.: collaborator

Study Sites (75)

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

Saint Jude Heritage Medical Center

Fullerton, California, 92835, United States

Location

University of California Los Angeles

Los Angeles, California, 90404, United States

Location

UC San Diego

San Diego, California, 92093, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Coastal Integrative Cancer Care

San Luis Obispo, California, 93401, United States

Location

Central Coast Medical Oncology

Santa Maria, California, 93454, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Rocky Mountain Cancer Centers

Lakewood, Colorado, 80228, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Altus Research

Lake Worth, Florida, 33461, United States

Location

University of Miami Hospital & Clinics Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

UF Health Cancer Center

Orlando, Florida, 32806, United States

Location

Horizon BioAdvance

Lafayette, Indiana, 47905, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89014, United States

Location

Women's Cancer Care Associates

Albany, New York, 12208, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Hope - A Woman's Cancer Institute

Asheville, North Carolina, 28006, United States

Location

University of Cincinnati Physicians Company

Cincinnati, Ohio, 45206, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73019, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

Flinders Cancer Clinic - Flinders Medical Centre (FMC)

Bedford Park, South Australia, 5042, Australia

Location

Mercy Hospital for Women

Heidelberg, Victoria, 3084, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3052, Australia

Location

Crown Princess Mary Cancer Centre (Westmead Hospital)

Westmead, Wentworthville, NSW 2145, Australia

Location

Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N4N2, Canada

Location

Cross Cancer Centre

Edmonton, Alberta, T6G1Z2, Canada

Location

British Columbia Cancer Agency

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BC Cancer Agency - Fraser Valley Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

Vancouver Cancer Centre, British Columbia Cancer Agency (BCCA)

Vancouver, British Columbia, V5Z4E6, Canada

Location

London Regional Cancer Centre

London, Ontario, N6A4L6, Canada

Location

Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

Centre Hospitalier de L'Universite de Montreal

Montreal, Quebec, H2L 4M1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

CHU de Québec - Université Laval

Québec, G1R 2J6, Canada

Location

Institut Bergonie

Bordeaux, Aquitaine, 33076, France

Location

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69373, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, 69495, France

Location

Institut Claudius Regaud

Toulouse, Midi-Pyrenees, 31052, France

Location

Centre Catherine de Sienne

Nantes, Pays de la Loire Region, 44202, France

Location

Hopital Tenon

Paris, Île-de-France Region, 75020, France

Location

Hôpital Européen Georges-Pompidou

Paris, Île-de-France Region, 75908, France

Location

Institut de cancerologie Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

Location

Hospital Vall d'Hebron

Barcelona, 8035, Spain

Location

Instituto Valencia de Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G120YN, United Kingdom

Location

Royal Marsden Sutton Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

St James University Hospital

Leeds, West Yorkshire, LS97TF, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB20QQ, United Kingdom

Location

Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, W120HS, United Kingdom

Location

University College London

London, W1T4TJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M204BX, United Kingdom

Location

Sir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care

Newcastle upon Tyne, NE77DN, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 35397664 DERIVED

• 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.

  PMID: 35170751 DERIVED

• Swisher EM, Kwan TT, Oza AM, Tinker AV, Ray-Coquard I, Oaknin A, Coleman RL, Aghajanian C, Konecny GE, O'Malley DM, Leary A, Provencher D, Welch S, Chen LM, Wahner Hendrickson AE, Ma L, Ghatage P, Kristeleit RS, Dorigo O, Musafer A, Kaufmann SH, Elvin JA, Lin DI, Chambers SK, Dominy E, Vo LT, Goble S, Maloney L, Giordano H, Harding T, Dobrovic A, Scott CL, Lin KK, McNeish IA. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2). Nat Commun. 2021 May 3;12(1):2487. doi: 10.1038/s41467-021-22582-6.

  PMID: 33941784 DERIVED

• Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmana J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. doi: 10.1136/ijgc-2019-000623.

  PMID: 31685558 DERIVED

• Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. doi: 10.1016/S1470-2045(16)30559-9. Epub 2016 Nov 29.

  PMID: 27908594 DERIVED

Related Links

• ARIEL trials website

MeSH Terms

Conditions

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

Interventions

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

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: July 3, 2013
• Study Start: October 30, 2013
• Primary Completion: November 5, 2019
• Study Completion: September 28, 2021
• Last Updated: June 12, 2023
• Results First Posted: July 13, 2021

Record last verified: 2023-06

Locations

US (36); CA (11); GB (9); AU (8); FR (8); ES (3)