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A Study of Rucaparib as Switch Maintenance Following Platinum-Based Chemotherapy in Patients With Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer (ARIEL3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01968213
Recruitment Status : Active, not recruiting
First Posted : October 23, 2013
Results First Posted : August 3, 2018
Last Update Posted : June 10, 2022
Sponsor:
Collaborators:
Foundation Medicine
Myriad Genetics, Inc.
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Brief Summary:
Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer Drug: Rucaparib Drug: Placebo 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). Clinical data have shown that ovarian cancer patients with and without evidence of a gBRCA mutation benefit from treatment with a PARP and that maintenance treatment with a PARP inhibitor following a response to platinum-based treatment increases PFS in patients with ovarian cancer. While patients with a BRCA mutation derived the most benefit, patients without evidence of a BRCA mutation also derived significant benefit.

Patients enrolled into this study will be stratified into 3 groups based on tumor HRD status. The purpose of this study is to identify which of these groups of patients will most likely benefit from treatment with rucaparib. It is anticipated that rucaparib will provide therapeutic benefit and increase PFS in patients with HRD associated with a BRCA gene mutation or other HR gene alteration.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 564 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous and Endometrioid Ovarian Cancer (ARIEL3)
Actual Study Start Date : April 7, 2014
Actual Primary Completion Date : April 1, 2017
Estimated Study Completion Date : December 1, 2022


Arm Intervention/treatment
Experimental: Rucaparib
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
Drug: Rucaparib
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
Other Name: CO-338; PF 01367338, AG 14699

Placebo Comparator: Placebo
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
Drug: Placebo
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.




Primary Outcome Measures :
  1. Disease Progression According to RECIST Version 1.1, as Assessed by the Investigator, or Death From Any Cause (Investigator Progression Free Survival as Per invPFS) [ Time Frame: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Study data collection expected to last for ~3 years. ]
    Progression-free survival by Investigator (invPFS) is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever occurs first. Progressive disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).


Secondary Outcome Measures :
  1. Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS) [ Time Frame: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Study data collection expected to last for ~3 years. ]
    To evaluate PFS by RECIST, as assessed by independent radiology review (IRR)

  2. Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18 [ Time Frame: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Study data collection expected to last for ~3 years. ]
    The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related symptoms and is based on numerical point scoring of symptoms. The DRS-P subscale of the questionnaire is specifically designed to assess physical symptoms of ovarian cancer and evaluate changes in the subscale point score in individual assessments over time. This study looked at the time to a 4-point reduction in subscale score as an indicator of improvement in disease-related physical symptoms on cancer therapy.

  3. Time to an 8-point Decrease in the Total Score of the FOSI-18 [ Time Frame: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Study data collection expected to last for ~3 years. ]
    The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related physical, emotional and treatment-related symptoms, and is based on numerical point scoring of symptoms. The questionnaire is designed to evaluate changes in the total score in individual assessments over time. This study looked at the time to an 8-point reduction in the total score as an indicator of improvement in disease-related symptoms on cancer therapy

  4. Overall Survival (OS) [ Time Frame: Continuously for ~5 years after patient enrolls into study. ]
    The final OS analysis has not been performed yet and will be performed when 70% of the events have been collected.

  5. Individual Model Parameter Estimates of Rucaparib and Covariates Identification [ Time Frame: Study data collection expected to last for ~7 months. ]
    Concentration summary statistics



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer.
  • Received ≥2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial.
  • Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen.
  • Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response.
  • For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response.
  • Have sufficient archival tumor tissue for analysis.

Exclusion Criteria:

  • History of prior cancer except for non-melanoma skin cancer, breast cancer curatively > 3 years ago, curatively treated solid tumor (>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer.
  • Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible.
  • Untreated or symptomatic central nervous system metastases.
  • Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drug.
  • Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01968213


Locations
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United States, Arizona
University of Arizona Cancer Center
Tucson, Arizona, United States, 85704
United States, California
Saint Jude Heritage Medical Center
Fullerton, California, United States, 92835
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
University of California San Francisco (UCSF)
San Francisco, California, United States, 94158
Coastal Integrative Cancer Care
San Luis Obispo, California, United States, 93422
Central Coast Medical Oncology
Santa Maria, California, United States, 93454
University of California Los Angeles (UCLA)
Santa Monica, California, United States, 90404
United States, Colorado
Rocky Mountain Cancer Centers
Lakewood, Colorado, United States, 80228
United States, Florida
Memorial Healthcare System
Hollywood, Florida, United States, 33021
Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Florida Hospital
Orlando, Florida, United States, 32804
United States, Maryland
Johns Hopkins Universty
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute - Wayne State University
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School of Medicine - Division of Gynaecological Oncology
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Hope Women's Cancer Centers
Asheville, North Carolina, United States, 28806
United States, Ohio
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
University of Washington at Seattle
Seattle, Washington, United States, 98109
Australia, New South Wales
Prince of Wales Hospital
Sydney, New South Wales, Australia, 2031
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Brisbane & Women's Hospital
Herston, Queensland, Australia, 4029
Australia, South Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
St John of God Hospital Subiaco
Subiaco, Western Australia, Australia, 608
Belgium
AZ St Augustinus
Antwerpen, Belgium, 2610
UZ Gent
Gent, Belgium, B-9000
UZ Leuven
Leuven, Belgium, 3000
Clinique Sainte-Elisabeth
Namur, Belgium, 5000
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G1Z2
Canada, Ontario
Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V5C2
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
CHUM Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, Canada, H2L4M1
Canada
Centre Hospitalier Universitaire de Québec
Quebec, Canada, G1R2J6
France
Centre Francois Baclesse
Caen Cedex 05, Basse-Normandie, France, 14076
Institut Gustave Roussy
Villejuif, Ile De France, France, 94805
Hôpital Européen Georges-Pompidou
Paris, Ile-de-France, France, 75908
Institut Claudius Regaud
Toulouse, Midi-Pyrenees, France, 31052
Centre Catherine de Sienne
Nantes Cedex, Pays De La Loire, France, 44202
Centre Leon Berard
Lyon, Rhone-Alpes, France, 69373
Centre Hospitalier Lyon Sud
Pierre Benite, Rhone-Alpes, France, 69495
Institute Bergonie
Bordeaux, France, 33076
Hospital Tenon
Paris, France, 75020
Germany
Klinikum Stuttgart
Stuttgart, Baden-Wuerttemberg, Germany, 70174
Klinikum Ludwigsburg-Bietigheim gGmbH
Ludwigsburg, Baden-Wuerttembert, Germany, 71640
Rotkreuzklinikum Muenchen gGmbH
Munich, Bavaria, Germany, 80637
Universitätsklinikum Frankfurt
Frankfurt am Main, Hessen, Germany, 60596
Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie
Wiesbaden, Hessen, Germany, 65199
Klinikum Chemnitz gGmbH
Chemnitz, Sachsen, Germany, 09116
Technische Universität Dresden
Dresden, Sachsen, Germany, 01307
Israel
Rambam Health Care Campus
Haifa, Israel, 31096
Lady Davis Carmel Medical Center
Haifa, Israel
Rabin Medical Center
Petach-Tikva, Israel, 49100
Oncology Institute, Sheba Medical Center
Ramat Gan, Israel, 52621
Sourasky Medical Center
Tel-Aviv, Israel, 64239
Assaf Harofeh M.C.
Zerifin, Israel, 70300
Italy
Oncology Unit City Hospital degli Infermi
Faenza, Ravenna, Italy, 48018
Arcispedale Santa Maria Nuova IRCCS
Reggio Emilia, Reggio Nella Emilia, Italy, 42100
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
Bologna, Italy, 40138
Fondazione IRCCS National Cancer Institute
Milan, Italy, 20133
Instituto Europeo di Oncologia
Milan, Italy, 20141
Azienda Ospedaliero Universitaria Policlinico di Modena
Modena, Italy, 41124
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Napoli, Italy, 80131
Policlinico Universitario Agostino Gemelli
Roma, Italy, 00158
New Zealand
Auckland City Hospital
Auckland, Grafton, New Zealand, 1023
Palmsteron North Hospital
Palmerston North, Manawatu, New Zealand, 4442
Wellington Hospital
Newtown, Wellington, New Zealand, 6021
Spain
Hospital Central de Asturias
Oviedo, Asturias, Spain, 33011
Centro Oncologico de Galica
A Coruna, Spain, 15009
Hospital Vall D'Hebron
Barcelona, Spain, 8035
Hospital Ramón y Cajal
Madrid, Spain, 28034
Hospital Universitario San Carlos
Madrid, Spain, 28040
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
Madrid, Spain, 28050
Hospital Regional Universitario Carlos Haya de Malaga
Malaga, Spain, 29011
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
Instituto Valencia de Oncologia-Fundacion
Valencia, Spain, 46009
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
United Kingdom
Royal Marsden Hospital
London, England, United Kingdom, SW3 6JJ
Belfast City Hospital
Belfast, Northern Ireland, United Kingdom, BT9 7AB
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G120YN
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, United Kingdom, SM2 5PT
St. James University Hospital
Leeds, West Yorkshire, United Kingdom, LS97TF
Addenbrookes Hospital
Cambridge, United Kingdom, CB20QQ
Barts Health NHS Trust
London, United Kingdom, EC1M6BQ
Imperial College Healthcare NHS Trust
London, United Kingdom, W120HS
Sarah Cannon Reserach Institute UK
London, United Kingdom, W1G6AD
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
Myriad Genetics, Inc.
Investigators
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Study Director: Heidi Giordano Clovis Oncology, Inc.
  Study Documents (Full-Text)

Documents provided by Clovis Oncology, Inc.:
Study Protocol  [PDF] July 7, 2016
Statistical Analysis Plan  [PDF] April 21, 2017

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01968213    
Other Study ID Numbers: CO-338-014
First Posted: October 23, 2013    Key Record Dates
Results First Posted: August 3, 2018
Last Update Posted: June 10, 2022
Last Verified: June 2022
Keywords provided by Clovis Oncology, Inc.:
ARIEL3
ARIEL 3
platinum sensitive
PARP Inhibitor
rucaparib
homologous recombination
homologous recombination deficiency
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
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents