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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Foundation Medicine
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT01891344
First received: June 20, 2013
Last updated: July 5, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Ovarian Cancer
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Drug: Oral rucaparib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 1) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]
  • ORR by RECIST v1.1 (PART 2) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ORR by RECIST v1.1 (PART 1) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years (RECIST v1.1). ] [ Designated as safety issue: No ]
  • Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 2) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]
  • ORR by RECIST v1.1 and GCIG CA-125 criteria [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]
  • Duration of response per RECIST v1.1 [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events, clinical laboratory abnormalities, and dose modifications [ Time Frame: Every day starting with signing of consent until 28 days after discontinuation of treatment; study data collection expected to last for ~2 years ] [ Designated as safety issue: Yes ]
  • Trough (Cmin) level rucaparib concentrations [ Time Frame: 2 weeks, 1 month, 2 months and 3 months after 1st dose ] [ Designated as safety issue: No ]
  • Overall Survival (PART 2) [ Time Frame: study data collection expected to last for ~2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 480
Study Start Date: September 2013
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ovarian cancer
rucaparib
Drug: Oral rucaparib
600 mg BID
Other Names:
  • CO-338
  • PF 01367338
  • AG 14699

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.

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 (currently enrolling): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

The following eligibility criteria pertain to patients enrolling into PART 2 of the study:

Inclusion:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01891344

  Hide Study Locations
Locations
United States, Alaska
Providence Alaska Medical Center
Anchorage, Alaska, United States, 99508
United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85719
United States, California
Saint Jude Heritage Medical Center
Fullerton, California, United States, 92835
University of California Los Angeles
Los Angeles, California, United States, 90404
Palo Alto Medical Foundation Group
Palo Alto, California, United States, 94304
UC San Diego
San Diego, California, United States, 92093
California Pacific Medical Center
San Francisco, California, United States, 94115
University of California, San Francisco
San Francisco, California, United States, 94158
Coastal Integrative Cancer Care
San Luis Obispo, California, United States, 93401
Central Coast Medical Oncology
Santa Maria, California, United States, 93454
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Rocky Mountain Cancer Centers
Lakewood, Colorado, United States, 80228
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
Altus Research
Lake Worth, Florida, United States, 33461
University of Miami Hospital & Clinics Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Adventist Health System
Orlando, Florida, United States, 32804
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
UF Health Cancer Center
Orlando, Florida, United States, 32806
United States, Indiana
Horizon BioAdvance
Lafayette, Indiana, United States, 47905
United States, Kentucky
Norton Cancer Institute
Louisville, Kentucky, United States, 40241
United States, Maryland
Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nevada
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, United States, 89014
United States, New York
Women's Cancer Care
Albany, New York, United States, 12208
New York University Langone Medical Center
New York, New York, United States, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
University of Cincinnati Physicians Company
Cincinnati, Ohio, United States, 45219
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43210
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73019
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
UPMC Cancer Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Australia, New South Wales
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia, 2065
Prince of Wales Hospital
Sydney, New South Wales, Australia, 2031
Australia, Queensland
Royal Brisbane & Women's Hospital
Herston, Queensland, Australia, 4029
Australia, South Australia
Flinders Cancer Clinic - Flinders Medical Centre (FMC)
Bedfork Park, South Australia, Australia, 5042
Australia, Victoria
Mercy Hospital for Women
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Australia
Crown Princess Mary Cancer Centre
Westmead, Australia
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N4N2
Cross Cancer Centre
Edmonton, Alberta, Canada, T6G1Z2
Canada, British Columbia
British Columbia Cancer Agency
Kelowna, British Columbia, Canada, V1Y 5L3
BC Cancer Agency - Fraser Valley Centre
Surrey, British Columbia, Canada, V3V 1Z2
Vancouver Cancer Centre, British Columbia Cancer Agency (BCCA)
Vancouver, British Columbia, Canada, V5Z4E6
Canada, Ontario
London Regional Cancer Centre
London, Ontario, Canada, N6A4L6
Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada, K1H8L6
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G2M9
Canada, Quebec
Centre Hospitalier de L'Universite de Montreal
Montreal, Quebec, Canada, H2L 4M1
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
CHU de Québec - Université Laval
Québec, Quebec, Canada, G1R 2J6
France
Institut Bergonie
Bordeaux, Aquitaine, France, 33076
Hopital Tenon
Paris, Ile-de-France, France, 75020
Hopital Hotel-Dieu
Paris, Ile-de-France, France, 75181
Institut de cancerologie Gustave Roussy
Villejuif, Ile-de-France, France, 94805
Institut Claudius Regaud
Toulouse, Midi-Pyrenees, France, 31052
Centre Catherine de Sienne
Nantes, Pays de la Loire, France, 44202
Centre Leon Berard
Lyon, Rhone-Alpes, France, 69373
Centre Hospitalier Lyon Sud
Pierre-Benite, Rhone-Alpes, France, 69495
Spain
Hospital Vall d'Hebron
Barcelona, Spain, 8035
Instituto Valencia de Oncologia
Valencia, Spain, 46009
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G120YN
Royal Marsden Sutton Hospital
Sutton, Surrey, United Kingdom, SM2 5PT
St James University Hospital
Leeds, West Yorkshire, United Kingdom, LS97TF
Addenbrooke's Hospital
Cambridge, United Kingdom, CB20QQ
Royal Marsden NHS Foundation Trust
Cambridge, United Kingdom
Imperial College Healthcare NHS Trust - Hammersmith Hospital
London, United Kingdom, W120HS
University College London
London, United Kingdom, W1T4TJ
The Christie NHS Foundation Trust
Manchester, United Kingdom, M204BX
Sir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care
Newcastle upon Tyne, United Kingdom, NE77DN
Sponsors and Collaborators
Clovis Oncology, Inc.
Foundation Medicine
  More Information

Additional Information:
Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01891344     History of Changes
Other Study ID Numbers: CO-338-017 
Study First Received: June 20, 2013
Last Updated: July 5, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Ministry of Health
Spain: Ministry of Health

Keywords provided by Clovis Oncology, Inc.:
rucaparib
PF 01367338
ovarian cancer
fallopian tube cancer
primary peritoneal cancer
peritoneal cancer
platinum sensitive
relapsed disease
PARP Inhibitor
homologous recombination
homologous recombination deficiency
genomic scarring
loss of heterozygosity
CO-338
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

Additional relevant MeSH terms:
Rucaparib
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Hypersensitivity
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Immune System Diseases
Neoplasms by Histologic Type
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 21, 2016