Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3) (ARIEL3)

June 7, 2023 updated by: zr Pharma & GmbH

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 )

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

564

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2031
        • Prince of Wales Hospital
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane & Women's Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Melbourne Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
      • Subiaco, Western Australia, Australia, 608
        • St John of God Hospital Subiaco
  • Belgium
      • Antwerpen, Belgium, 2610
        • AZ St Augustinus
      • Gent, Belgium, B-9000
        • UZ Gent
      • Leuven, Belgium, 3000
        • UZ Leuven
      • Namur, Belgium, 5000
        • Clinique Sainte-Elisabeth
  • Canada
      • Quebec, Canada, G1R2J6
        • Centre Hospitalier Universitaire de Quebec
    • Alberta
      • Calgary, Alberta, Canada, T2N4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G1Z2
        • Cross Cancer Institute
    • Ontario
      • Hamilton, Ontario, Canada, L8V5C2
        • Juravinski Cancer Centre
      • London, Ontario, Canada, N6A4L6
        • London Regional Cancer Centre
      • Ottawa, Ontario, Canada, K1H8L6
        • Ottawa Hospital Cancer Centre
      • Toronto, Ontario, Canada, M5G2M9
        • Princess Margaret Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H2L4M1
        • CHUM Centre Hospitalier de l'Université de Montréal
  • France
      • Bordeaux, France, 33076
        • Institute Bergonie
      • Paris, France, 75020
        • Hospital Tenon
    • Basse-Normandie
      • Caen Cedex 05, Basse-Normandie, France, 14076
        • Centre Francois Baclesse
    • Ile De France
      • Villejuif, Ile De France, France, 94805
        • Institut Gustave Roussy
    • Ile-de-France
      • Paris, Ile-de-France, France, 75908
        • Hôpital Européen Georges-Pompidou
    • Midi-Pyrenees
      • Toulouse, Midi-Pyrenees, France, 31052
        • Institut Claudius Regaud
    • Pays De La Loire
      • Nantes Cedex, Pays De La Loire, France, 44202
        • Centre Catherine de Sienne
    • Rhone-Alpes
      • Lyon, Rhone-Alpes, France, 69373
        • Centre Leon Berard
      • Pierre Benite, Rhone-Alpes, France, 69495
        • Centre Hospitalier Lyon Sud
  • Germany
    • Baden-Wuerttemberg
      • Stuttgart, Baden-Wuerttemberg, Germany, 70174
        • Klinikum Stuttgart
    • Baden-Wuerttembert
      • Ludwigsburg, Baden-Wuerttembert, Germany, 71640
        • Klinikum Ludwigsburg-Bietigheim gGmbH
    • Bavaria
      • Munich, Bavaria, Germany, 80637
        • Rotkreuzklinikum Muenchen gGmbH
    • Hessen
      • Frankfurt am Main, Hessen, Germany, 60596
        • Universitätsklinikum Frankfurt
      • Wiesbaden, Hessen, Germany, 65199
        • Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie
    • Sachsen
      • Chemnitz, Sachsen, Germany, 09116
        • Klinikum Chemnitz gGmbH
      • Dresden, Sachsen, Germany, 01307
        • Technische Universität Dresden
  • Israel
      • Haifa, Israel, 31096
        • Rambam Health Care Campus
      • Haifa, Israel
        • Lady Davis Carmel Medical Center
      • Petach-Tikva, Israel, 49100
        • Rabin Medical Center
      • Ramat Gan, Israel, 52621
        • Oncology Institute, Sheba Medical Center
      • Tel-Aviv, Israel, 64239
        • Sourasky Medical Center
      • Zerifin, Israel, 70300
        • Assaf Harofeh M.C.
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
      • Milan, Italy, 20141
        • Instituto Europeo di Oncologia
      • Milan, Italy, 20133
        • Fondazione IRCCS National Cancer Institute
      • Modena, Italy, 41124
        • Azienda Ospedaliero Universitaria Policlinico di Modena
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori IRCCS Fondazione Pascale
      • Roma, Italy, 00158
        • Policlinico Universitario Agostino Gemelli
    • Ravenna
      • Faenza, Ravenna, Italy, 48018
        • Oncology Unit City Hospital degli Infermi
    • Reggio Nella Emilia
      • Reggio Emilia, Reggio Nella Emilia, Italy, 42100
        • Arcispedale Santa Maria Nuova IRCCS
  • New Zealand
    • Grafton
      • Auckland, Grafton, New Zealand, 1023
        • Auckland City Hospital
    • Manawatu
      • Palmerston North, Manawatu, New Zealand, 4442
        • Palmsteron North Hospital
    • Wellington
      • Newtown, Wellington, New Zealand, 6021
        • Wellington Hospital
  • Spain
      • A Coruna, Spain, 15009
        • Centro Oncologico de Galica
      • Barcelona, Spain, 8035
        • Hospital Vall d'Hebron
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spain, 28040
        • Hospital Universitario San Carlos
      • Madrid, Spain, 28050
        • Centro Integral Oncologico Clara Campal, Hospital de Madrid Norte-San Chinarro
      • Malaga, Spain, 29011
        • Hospital Regional Universitario Carlos Haya de Malaga
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain, 46009
        • Instituto Valencia de Oncologia-Fundacion
    • Asturias
      • Oviedo, Asturias, Spain, 33011
        • Hospital Central de Asturias
  • United Kingdom
      • Cambridge, United Kingdom, CB20QQ
        • Addenbrookes Hospital
      • London, United Kingdom, EC1M6BQ
        • Barts Health NHS Trust
      • London, United Kingdom, W120HS
        • Imperial College Healthcare NHS Trust
      • London, United Kingdom, W1G6AD
        • Sarah Cannon Reserach Institute UK
      • London, United Kingdom, W1T4TJ
        • University College London
      • Manchester, United Kingdom, M204BX
        • The Christie NHS Foundation Trust
      • Newcastle Upon Tyne, United Kingdom, NE77DN
        • Sir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care
    • England
      • London, England, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, BT9 7AB
        • Belfast City Hospital
    • Scotland
      • Glasgow, Scotland, United Kingdom, G120YN
        • Beatson West of Scotland Cancer Centre
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS97TF
        • St. James University Hospital
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85704
        • University of Arizona Cancer Center
    • California
      • Fullerton, California, United States, 92835
        • Saint Jude Heritage Medical Center
      • Sacramento, California, United States, 95817
        • UC Davis Comprehensive Cancer Center
      • San Francisco, California, United States, 94158
        • University of California San Francisco (UCSF)
      • San Luis Obispo, California, United States, 93422
        • Coastal Integrative Cancer Care
      • Santa Maria, California, United States, 93454
        • Central Coast Medical Oncology
      • Santa Monica, California, United States, 90404
        • University of California Los Angeles (UCLA)
    • Colorado
      • Lakewood, Colorado, United States, 80228
        • Rocky Mountain Cancer Centers
    • Florida
      • Hollywood, Florida, United States, 33021
        • Memorial Healthcare System
      • Miami, Florida, United States, 33136
        • Sylvester Comprehensive Cancer Center
      • Orlando, Florida, United States, 32804
        • Florida Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Universty
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute - Wayne State University
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine - Division of Gynaecological Oncology
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
    • North Carolina
      • Asheville, North Carolina, United States, 28806
        • Hope Women's Cancer Centers
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Wexner Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington at Seattle

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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. Total follow-up was up to approximately 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).
Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 3 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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. Total follow-up was up to approximately 8.2 years.
To evaluate PFS by RECIST v1.1, as assessed by independent radiology review (IRR).
Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 8.2 years.
Overall Survival (OS)
Time Frame: All patients were followed for survival up to approximately 8.2 years.
Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive.
All patients were followed for survival up to approximately 8.2 years.
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. Total follow-up was up to approximately 6.4 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.
Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
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. Total follow-up was up to approximately 6.4 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.
Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
Individual Model Parameter Estimates of Rucaparib and Covariates Identification
Time Frame: Study data collection occurred over approximately 7 months.
Concentration summary statistics
Study data collection occurred over approximately 7 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

zr Pharma & GmbH

Collaborators

Foundation Medicine
Myriad Genetics, Inc.

Investigators

  • Study Director: Heidi Giordano, Clovis Oncology, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2014

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

July 7, 2022

Study Registration Dates

First Submitted

October 17, 2013

First Submitted That Met QC Criteria

October 18, 2013

First Posted (Estimated)

October 23, 2013

Study Record Updates

Last Update Posted (Actual)

June 9, 2023

Last Update Submitted That Met QC Criteria

June 7, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CO-338-014
  • 2013-000518-39 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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