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

NCT ID: NCT01891344

Last Updated: 2023-06-12

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

491 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-30

Study Completion Date

2021-09-28

Brief Summary

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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.

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.

Clinical data with PARP inhibitors indicate there is an ovarian cancer patient population beyond just those with germline BRCA (gBRCA) mutations that may benefit from treatment with a PARP inhibitor. This study will define a molecular signature of HRD in ovarian cancer that correlates with response to rucaparib and enables selection of appropriate ovarian cancer patients for treatment with rucaparib. The HRD signature will be based on an association between the extent of genomic scarring (a downstream consequence of HRD) in a patient's tumor and observed clinical benefit from rucaparib treatment. Genomic scarring can be assessed by quantifying the extent of loss of heterozygosity across the tumor genome (tumor genomic LOH). One of the main advantages of detecting tumor genomic LOH is that it can identify HRD tumors regardless of the underlying mechanisms, which include both known (i.e., BRCA mutations) and unknown genetic and other mechanisms.

Once determined, this signature will be prospectively applied to ARIEL2 PART 2 and ARIEL3. This Phase 2 study (ARIEL2) will also compare archival versus recently collected tumor tissue in order to validate the use of archival tumor tissue for assessment of HRD status in ARIEL3.

This study will include 2 parts:

PART 1 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received ≥1 prior platinum-based regimen and had platinum-sensitive disease

PART 2 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens

Conditions

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Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ovarian cancer

rucaparib

Group Type EXPERIMENTAL

Oral rucaparib

Intervention Type DRUG

600 mg BID

Interventions

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Oral rucaparib

600 mg BID

Intervention Type DRUG

Other Intervention Names

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CO-338 PF 01367338 AG 14699

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion:

* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Foundation Medicine

INDUSTRY

Sponsor Role collaborator

Myriad Genetics, Inc.

INDUSTRY

Sponsor Role collaborator

pharmaand GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status

University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

Saint Jude Heritage Medical Center

Fullerton, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

UC San Diego

San Diego, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Coastal Integrative Cancer Care

San Luis Obispo, California, United States

Site Status

Central Coast Medical Oncology

Santa Maria, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Rocky Mountain Cancer Centers

Lakewood, Colorado, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

Altus Research

Lake Worth, Florida, United States

Site Status

University of Miami Hospital & Clinics Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Florida Hospital Cancer Institute

Orlando, Florida, United States

Site Status

UF Health Cancer Center

Orlando, Florida, United States

Site Status

Horizon BioAdvance

Lafayette, Indiana, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Site Status

Women's Cancer Care Associates

Albany, New York, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Hope - A Woman's Cancer Institute

Asheville, North Carolina, United States

Site Status

University of Cincinnati Physicians Company

Cincinnati, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Royal North Shore Hospital

Saint Leonards, New South Wales, Australia

Site Status

Prince of Wales Hospital

Sydney, New South Wales, Australia

Site Status

Royal Brisbane & Women's Hospital

Herston, Queensland, Australia

Site Status

Flinders Cancer Clinic - Flinders Medical Centre (FMC)

Bedford Park, South Australia, Australia

Site Status

Mercy Hospital for Women

Heidelberg, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Crown Princess Mary Cancer Centre (Westmead Hospital)

Westmead, Wentworthville, Australia

Site Status

Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

Cross Cancer Centre

Edmonton, Alberta, Canada

Site Status

British Columbia Cancer Agency

Kelowna, British Columbia, Canada

Site Status

BC Cancer Agency - Fraser Valley Centre

Surrey, British Columbia, Canada

Site Status

Vancouver Cancer Centre, British Columbia Cancer Agency (BCCA)

Vancouver, British Columbia, Canada

Site Status

London Regional Cancer Centre

London, Ontario, Canada

Site Status

Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Centre Hospitalier de L'Universite de Montreal

Montreal, Quebec, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

CHU de Québec - Université Laval

Québec, , Canada

Site Status

Institut Bergonie

Bordeaux, Aquitaine, France

Site Status

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Site Status

Institut Claudius Regaud

Toulouse, Midi-Pyrenees, France

Site Status

Centre Catherine de Sienne

Nantes, Pays de la Loire Region, France

Site Status

Hopital Tenon

Paris, Île-de-France Region, France

Site Status

Hôpital Européen Georges-Pompidou

Paris, Île-de-France Region, France

Site Status

Institut de cancerologie Gustave Roussy

Villejuif, Île-de-France Region, France

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Instituto Valencia de Oncologia

Valencia, , Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Site Status

Royal Marsden Sutton Hospital

Sutton, Surrey, United Kingdom

Site Status

St James University Hospital

Leeds, West Yorkshire, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust - Hammersmith Hospital

London, , United Kingdom

Site Status

University College London

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

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

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Australia Canada France Spain United Kingdom

References

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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)

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.

Reference Type DERIVED
PMID: 33941784 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31685558 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27908594 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://arielstudy.com/

ARIEL trials website

Other Identifiers

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2013-000517-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CO-338-017

Identifier Type: -

Identifier Source: org_study_id

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