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

June 7, 2023 updated by: zr Pharma & GmbH

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)

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.

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). 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

Study Type

Interventional

Enrollment (Actual)

491

Phase

  • Phase 2

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
      • Saint Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
      • Sydney, New South Wales, Australia, 2031
        • Prince of Wales Hospital
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane & Women's Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Cancer Clinic - Flinders Medical Centre (FMC)
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Mercy Hospital for Women
      • Parkville, Victoria, Australia, 3052
        • Royal Melbourne Hospital
    • Wentworthville
      • Westmead, Wentworthville, Australia, NSW 2145
        • Crown Princess Mary Cancer Centre (Westmead Hospital)
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Charles Gairdner Hospital
  • Canada
      • Québec, Canada, G1R 2J6
        • CHU de Québec - Université Laval
    • Alberta
      • Calgary, Alberta, Canada, T2N4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G1Z2
        • Cross Cancer Centre
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
        • British Columbia Cancer Agency
      • Surrey, British Columbia, Canada, V3V 1Z2
        • BC Cancer Agency - Fraser Valley Centre
      • Vancouver, British Columbia, Canada, V5Z4E6
        • Vancouver Cancer Centre, British Columbia Cancer Agency (BCCA)
    • Ontario
      • 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, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H2L 4M1
        • Centre Hospitalier de l'Université de Montréal
  • France
    • Aquitaine
      • Bordeaux, Aquitaine, France, 33076
        • Institut Bergonie
    • Ile-de-France
      • Paris, Ile-de-France, France, 75908
        • Hôpital Européen Georges-Pompidou
      • Paris, Ile-de-France, France, 75020
        • Hôpital Tenon
      • Villejuif, Ile-de-France, France, 94805
        • Institut de Cancérologie Gustave Roussy
    • Midi-Pyrenees
      • Toulouse, Midi-Pyrenees, France, 31052
        • Institut Claudius Regaud
    • Pays De La Loire
      • Nantes, 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
  • Spain
      • Barcelona, Spain, 8035
        • Hospital Vall d'Hebron
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain, 46009
        • Instituto Valencia de Oncologia
  • United Kingdom
      • Cambridge, United Kingdom, CB20QQ
        • Addenbrooke's Hospital
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden NHS Foundation Trust
      • London, United Kingdom, W1T4TJ
        • University College London
      • London, United Kingdom, W120HS
        • Imperial College Healthcare NHS Trust - Hammersmith Hospital
      • 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
    • Scotland
      • Glasgow, Scotland, United Kingdom, G120YN
        • Beatson West of Scotland Cancer Centre
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Royal Marsden Sutton Hospital
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS97TF
        • St James University Hospital
  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Providence Alaska Medical Center
    • Arizona
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center
    • California
      • Fullerton, California, United States, 92835
        • Saint Jude Heritage Medical Center
      • Los Angeles, California, United States, 90404
        • University of California Los Angeles
      • San Diego, California, United States, 92093
        • UC San Diego
      • San Francisco, California, United States, 94158
        • University of California, San Francisco
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center
      • San Luis Obispo, California, United States, 93401
        • Coastal Integrative Cancer Care
      • Santa Maria, California, United States, 93454
        • Central Coast Medical Oncology
      • Stanford, California, United States, 94305
        • Stanford University
    • Colorado
      • Lakewood, Colorado, United States, 80228
        • Rocky Mountain Cancer Centers
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Jacksonville
      • Lake Worth, Florida, United States, 33461
        • Altus Research
      • Miami, Florida, United States, 33136
        • University of Miami Hospital & Clinics Sylvester Comprehensive Cancer Center
      • Orlando, Florida, United States, 32804
        • Florida Hospital Cancer Institute
      • Orlando, Florida, United States, 32806
        • UF Health Cancer Center
    • Indiana
      • Lafayette, Indiana, United States, 47905
        • Horizon BioAdvance
    • Kentucky
      • Louisville, Kentucky, United States, 40241
        • Norton Cancer Institute
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Kimmel Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nevada
      • Henderson, Nevada, United States, 89014
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Albany, New York, United States, 12208
        • Women's Cancer Care Associates
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • New York University Langone Medical Center
    • North Carolina
      • Asheville, North Carolina, United States, 28006
        • Hope - A Woman's Cancer Institute
    • Ohio
      • Cincinnati, Ohio, United States, 45206
        • University of Cincinnati Physicians Company
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Wexner Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73019
        • University of Oklahoma
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington - Seattle Cancer Care Alliance

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

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ovarian cancer
rucaparib
Drug: Oral rucaparib
600 mg BID
Other Names:
  • CO-338
  • PF 01367338
  • AG 14699

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)
Time Frame: 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.
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)
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)
Time Frame: 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.
The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or 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.
Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria
Time Frame: 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.
The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. 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. A response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.
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
Time Frame: 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 (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. 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.
Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)
Time Frame: 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) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, 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.
Overall Survival (Part 2 of Study)
Time Frame: 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.
Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.
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.
Steady State Trough (Cmin) Level Rucaparib Concentrations
Time Frame: Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks
Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available.
Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks

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.

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)

October 30, 2013

Primary Completion (Actual)

November 5, 2019

Study Completion (Actual)

September 28, 2021

Study Registration Dates

First Submitted

June 20, 2013

First Submitted That Met QC Criteria

June 28, 2013

First Posted (Estimated)

July 3, 2013

Study Record Updates

Last Update Posted (Actual)

June 12, 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-338-017
  • 2013-000517-20 (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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