Clinical trial NCT01968213: Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (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 )
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Keywords: 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
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
Collaborators: name: Foundation Medicine
name: Myriad Genetics, Inc.
First posted: 2013-10-23
Enrollment: 564
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: 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)
timeFrame: 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 outcomes:
measure: Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: All patients were followed for survival up to approximately 8.2 years.
measure: Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18
timeFrame: 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.
measure: Time to an 8-point Decrease in the Total Score of the FOSI-18
timeFrame: 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.
measure: Individual Model Parameter Estimates of Rucaparib and Covariates Identification
timeFrame: Study data collection occurred over approximately 7 months.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Fullerton
country: United States
facility: Saint Jude Heritage Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: San Luis Obispo
country: United States
facility: Coastal Integrative Cancer Care
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Universty
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute - Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Division of Gynaecological Oncology
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Asheville
country: United States
facility: Hope Women's Cancer Centers
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington at Seattle
state: Washington
city: Sydney
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John of God Hospital Subiaco
state: Western Australia
city: Antwerpen
country: Belgium
facility: AZ St Augustinus
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Namur
country: Belgium
facility: Clinique Sainte-Elisabeth
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CHUM Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Québec
city: Caen Cedex 05
country: France
facility: Centre Francois Baclesse
state: Basse-Normandie
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Ile De France
city: Paris
country: France
facility: Hôpital Européen Georges-Pompidou
state: Ile-de-France
city: Toulouse
country: France
facility: Institut Claudius Regaud
state: Midi-Pyrenees
city: Nantes Cedex
country: France
facility: Centre Catherine de Sienne
state: Pays De La Loire
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhone-Alpes
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone-Alpes
city: Bordeaux
country: France
facility: Institute Bergonie
city: Paris
country: France
facility: Hospital Tenon
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
state: Baden-Wuerttemberg
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg-Bietigheim gGmbH
state: Baden-Wuerttembert
city: Munich
country: Germany
facility: Rotkreuzklinikum Muenchen gGmbH
state: Bavaria
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
state: Hessen
city: Wiesbaden
country: Germany
facility: Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie
state: Hessen
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
state: Sachsen
city: Dresden
country: Germany
facility: Technische Universität Dresden
state: Sachsen
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Petach-Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Oncology Institute, Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofeh M.C.
city: Faenza
country: Italy
facility: Oncology Unit City Hospital degli Infermi
state: Ravenna
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova IRCCS
state: Reggio Nella Emilia
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
city: Milan
country: Italy
facility: Fondazione IRCCS National Cancer Institute
city: Milan
country: Italy
facility: Instituto Europeo di Oncologia
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Auckland
country: New Zealand
facility: Auckland City Hospital
state: Grafton
city: Palmerston North
country: New Zealand
facility: Palmsteron North Hospital
state: Manawatu
city: Newtown
country: New Zealand
facility: Wellington Hospital
state: Wellington
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
state: Asturias
city: A Coruna
country: Spain
facility: Centro Oncologico de Galica
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Instituto Valencia de Oncologia-Fundacion
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: Royal Marsden Hospital
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: Northern Ireland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Leeds
country: United Kingdom
facility: St. James University Hospital
state: West Yorkshire
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Sarah Cannon Reserach Institute UK
city: London
country: United Kingdom
facility: University College London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Sir Bobby Robson Cancer trials research Centre, Northern Centre For Cancer Care
Study officials:
affiliation: Clovis Oncology, Inc.
name: Heidi Giordano
role: STUDY_DIRECTOR
References:
citation: Green ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
citation: Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
citation: Colombo N, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Meunier J, Cameron T, Maloney L, Goble S, Bedel J, Ledermann JA, Coleman RL. The effect of age on efficacy, safety and patient-centered outcomes with rucaparib: A post hoc exploratory analysis of ARIEL3, a phase 3, randomized, maintenance study in patients with recurrent ovarian carcinoma. Gynecol Oncol. 2020 Oct;159(1):101-111. doi: 10.1016/j.ygyno.2020.05.045. Epub 2020 Aug 26.
citation: Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. doi: 10.1016/S1470-2045(20)30061-9.
citation: 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.