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

Ovarian Cancer Clinical Trial

— ARIEL3  

Official title:

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 )

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01968213
• Other study ID #: CO-338-014
• Secondary ID: 2013-000518-39
• Status: Completed
• Phase: Phase 3
• Start date: April 7, 2014
• Est. completion date: July 7, 2022

Study information

• Verified date: June 2023
• Source: zr Pharma & GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 564
• Est. completion date: July 7, 2022
• Est. primary completion date: April 1, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	St John of God Hospital Subiaco	Subiaco	Western Australia
Australia	Prince of Wales Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	AZ St Augustinus	Antwerpen
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	Clinique Sainte-Elisabeth	Namur
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Centre	London	Ontario
Canada	CHUM Centre Hospitalier de l'Université de Montréal	Montreal	Quebec
Canada	Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Québec	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	Institute Bergonie	Bordeaux
France	Centre Francois Baclesse	Caen Cedex 05	Basse-Normandie
France	Centre Leon Berard	Lyon	Rhone-Alpes
France	Centre Catherine de Sienne	Nantes Cedex	Pays De La Loire
France	Hôpital Européen Georges-Pompidou	Paris	Ile-de-France
France	Hospital Tenon	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite	Rhone-Alpes
France	Institut Claudius Regaud	Toulouse	Midi-Pyrenees
France	Institut Gustave Roussy	Villejuif	Ile De France
Germany	Klinikum Chemnitz gGmbH	Chemnitz	Sachsen
Germany	Technische Universität Dresden	Dresden	Sachsen
Germany	Universitätsklinikum Frankfurt	Frankfurt am Main	Hessen
Germany	Klinikum Ludwigsburg-Bietigheim gGmbH	Ludwigsburg	Baden-Wuerttembert
Germany	Rotkreuzklinikum Muenchen gGmbH	Munich	Bavaria
Germany	Klinikum Stuttgart	Stuttgart	Baden-Wuerttemberg
Germany	Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie	Wiesbaden	Hessen
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Rabin Medical Center	Petach-Tikva
Israel	Oncology Institute, Sheba Medical Center	Ramat Gan
Israel	Sourasky Medical Center	Tel-Aviv
Israel	Assaf Harofeh M.C.	Zerifin
Italy	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi	Bologna
Italy	Oncology Unit City Hospital degli Infermi	Faenza	Ravenna
Italy	Fondazione IRCCS National Cancer Institute	Milan
Italy	Instituto Europeo di Oncologia	Milan
Italy	Azienda Ospedaliero Universitaria Policlinico di Modena	Modena
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli
Italy	Arcispedale Santa Maria Nuova IRCCS	Reggio Emilia	Reggio Nella Emilia
Italy	Policlinico Universitario Agostino Gemelli	Roma
New Zealand	Auckland City Hospital	Auckland	Grafton
New Zealand	Wellington Hospital	Newtown	Wellington
New Zealand	Palmsteron North Hospital	Palmerston North	Manawatu
Spain	Centro Oncologico de Galica	A Coruna
Spain	Hospital Vall D'Hebron	Barcelona
Spain	Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario San Carlos	Madrid
Spain	Hospital Regional Universitario Carlos Haya de Malaga	Malaga
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Instituto Valencia de Oncologia-Fundacion	Valencia
United Kingdom	Belfast City Hospital	Belfast	Northern Ireland
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	St. James University Hospital	Leeds	West Yorkshire
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Marsden Hospital	London	England
United Kingdom	Sarah Cannon Reserach Institute UK	London
United Kingdom	University College London	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Sir Bobby Robson Cancer trials research Centre, Northern Centre For Cancer Care	Newcastle Upon Tyne
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United States	Hope Women's Cancer Centers	Asheville	North Carolina
United States	Johns Hopkins Universty	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Karmanos Cancer Institute - Wayne State University	Detroit	Michigan
United States	Saint Jude Heritage Medical Center	Fullerton	California
United States	Memorial Healthcare System	Hollywood	Florida
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Rocky Mountain Cancer Centers	Lakewood	Colorado
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Florida Hospital	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine - Division of Gynaecological Oncology	Saint Louis	Missouri
United States	University of California San Francisco (UCSF)	San Francisco	California
United States	Coastal Integrative Cancer Care	San Luis Obispo	California
United States	Central Coast Medical Oncology	Santa Maria	California
United States	University of California Los Angeles (UCLA)	Santa Monica	California
United States	University of Washington at Seattle	Seattle	Washington
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
zr Pharma & GmbH	Foundation Medicine, Myriad Genetics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Israel,  Italy,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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	Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS)	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.
Secondary	Overall Survival (OS)	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.
Secondary	Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18	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.
Secondary	Time to an 8-point Decrease in the Total Score of the FOSI-18	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.
Secondary	Individual Model Parameter Estimates of Rucaparib and Covariates Identification	Concentration summary statistics	Study data collection occurred over approximately 7 months.

External Links

•   ARIEL program website