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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 : August 1, 2019
Sponsor:
Collaborators:
Foundation Medicine
Myriad Genetics, Inc.
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE October 17, 2013
First Posted Date  ICMJE October 23, 2013
Results First Submitted Date  ICMJE May 8, 2018
Results First Posted Date  ICMJE August 3, 2018
Last Update Posted Date August 1, 2019
Study Start Date  ICMJE January 2014
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2018)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
Disease progression according to RECIST Version 1.1 (v1.1), as assessed by the investigator, or death from any cause (investigator Progression Free Survival or invPFS), in molecularly defined subgroups [ Time Frame: Screening, within 7 days prior to the end of every 3rd cycle of treament, and Treatment Discontinuation visit. Study data collection expected to last for ~3 years. ]
Change History Complete list of historical versions of study NCT01968213 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2018)
  • 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)
  • 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.
  • 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
  • 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.
  • Individual Model Parameter Estimates of Rucaparib and Covariates Identification [ Time Frame: Study data collection expected to last for ~7 months. ]
    Concentration summary statistics
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
  • Disease progression according to RECIST v1.1, as assessed by Independent Radiology Review (IRR), or death from any cause (irrPFS), in molecularly defined subgroups [ Time Frame: Screening, within 7 days prior to the end of every 3rd cycle of treament, and Treatment Discontinuation visit. Study data collection expected to last for ~3 years. ]
  • Time to a specified decrease in the DSR P subscale of the FOSI-18 patient reported outcome questionnaire [ 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. ]
  • Time to a specified decrease in the total score of the FOSI-18 patient reported outcome questionnaire [ 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. ]
  • Overall Survival (OS) [ Time Frame: Continuously for ~5 years after patient enrolls into study. ]
  • Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications [ Time Frame: Continuously for ~3 years after patient enrolls into study. ]
  • Individual model parameter estimates of rucaparib and covariates identification (PK) [ Time Frame: Cycle 1 Day 15, and Cycle 2 Day 1, Cycle 2 Day 15, Cycle 4 Day 1, and Cycle 7 Day 1. Study data collection expected to last for ~7 months. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous and Endometrioid Ovarian Cancer (ARIEL3)
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
Intervention  ICMJE
  • 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
  • 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.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Rucaparib
  • 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.
    Intervention: Drug: Placebo
Publications * Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12. Erratum in: Lancet. 2017 Oct 28;390(10106):1948.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 1, 2018)
564
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2013)
540
Estimated Study Completion Date  ICMJE June 2020
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Germany,   Israel,   Italy,   New Zealand,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01968213
Other Study ID Numbers  ICMJE CO-338-014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Clovis Oncology, Inc.
Study Sponsor  ICMJE Clovis Oncology, Inc.
Collaborators  ICMJE
  • Foundation Medicine
  • Myriad Genetics, Inc.
Investigators  ICMJE
Study Director: Heidi Giordano Clovis Oncology, Inc.
PRS Account Clovis Oncology, Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP