Clinical trial NCT02855944: ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients
Official title: ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Epithelial Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Keywords: ovarian cancer
fallopian tube cancer
primary peritoneal cancer
peritoneal cancer
platinum sensitive
relapsed disease
PARP Inhibitor
PARP
rucaparib
ruca
homologous recombination
homologous recombination deficiency
genomic scarring
loss of heterozygosity
CO-338
PF-01367338
PF 01367338
CO-338-043
platinum sensitive ovarian cancer
platinum sensitive fallopian tube cancer
platinum sensitive primary peritoneal cancer
platinum sensitive peritoneal cancer
gynecological cancer
Clovis
Clovis oncology
ARIEL2
ARIEL 2
ARIEL-2
ARIEL-3
ARIEL 3
ARIEL3
ARIEL4
ARIEL-4
ARIEL 4
A4
advanced OC
platinum resistant ovarian cancer
platinum resistant primary ovarian cancer
Rubraca
High grade serous
Partially platinum sensitive
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
Collaborators: name: Foundation Medicine
First posted: 2016-08-04
Enrollment: 349
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: The purpose of this study is to determine how patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib versus chemotherapy.

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.

While PARP inhibitors have demonstrated consistent robust clinical activity in patients with relapsed ovarian cancer associated with HRD, prospective studies evaluating efficacy and safety of PARPi versus standard of care chemotherapy have been limited. The primary purpose of this Phase 3 study is to compare the efficacy and safety of rucaparib versus chemotherapy as treatment for relapsed ovarian cancer in patients with a deleterious BRCA1/2 mutation in their tumor.

Eligibility criteria: Inclusion Criteria:

* Be 18 years of age at the time the informed consent form is signed
* 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 ≥ 2 prior chemotherapy regimens and have relapsed or progressive disease as confirmed by radiologic assessment
* Have biopsiable and evaluable disease. Note: biopsy is optional for patients known to harbor a BRCA1/2 mutation
* Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses

Exclusion Criteria:

* 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
* Women who are pregnant or breast feeding
* Hospitalization for bowel obstruction within 3 months prior to enrollment

Primary outcomes:
measure: Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)
timeFrame: Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
measure: Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)
timeFrame: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
Secondary outcomes:
measure: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)
timeFrame: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
measure: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)
timeFrame: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
measure: Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)
timeFrame: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
measure: Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)
timeFrame: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
measure: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)
timeFrame: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
measure: Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)
timeFrame: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.
measure: Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population)
timeFrame: Baseline to the end of Cycle 6, or up to approximately 6 months
measure: Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population)
timeFrame: Baseline to the end of Cycle 6, or up to approximately 6 months
measure: Overall Survival (Efficacy Population)
timeFrame: All patients were followed for survival up to approximately 3.5 years.
measure: Overall Survival (ITT Population)
timeFrame: All patients were followed for survival up to approximately 3.5 years.
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Fortaleza
country: Brazil
facility: Hospital Haroldo Juacaba Instituto do Cancer do Ceara
state: Ceara
city: Curitiba
country: Brazil
facility: Instituto de Oncologia do Parana (IOP)
state: Parana
city: Porto Alegre
country: Brazil
facility: União Brasileira de Educação e Assistência / Hospital São Lucas da PUCRS
state: RIO Grande DO SUL
city: Florianópolis
country: Brazil
facility: CEPON-Centro de pesquisas Oncologicas
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital do Cancer de Barretos
state: SAO Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer Hospital do Câncer II
city: Sao Paulo
country: Brazil
facility: Hospital Pérola Byington - Centro de Referência da Saúde da Mulher
city: Sao Paulo
country: Brazil
facility: Hospital São Camilo
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de L'Universite de Montreal (CHUM)
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie CHUS
state: Quebec
city: Brno
country: Czechia
facility: Masarykuv Onkologicky Ustav, Oddeleni komplexni klinicke onkologie
state: Jihormoravsky KRAJ
city: Praha 5
country: Czechia
facility: Fakultni Nemocnice v Motole
state: Praha
city: Ostrava
country: Czechia
facility: Fakultní Nemocnice Ostrava
city: Praha
country: Czechia
facility: Všeobecná Fakultní Nemocnice v Praze
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
state: Hajdu-bihar
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Petach-Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center, Oncology Dept.
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
city: Candiolo
country: Italy
facility: Istituto per la Ricerca e la Cura del Cancro Istituto di Candiolo
city: Catania
country: Italy
facility: AO per l'emergenza Cannizzaro
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale per lo studio e la cura dei tumori "Fondazione Pascale" Oncologia Medica
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Grzybnica
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna Sp z o.o.
state: West Pomeranian Voivodeship
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Olsztynie
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Pozna
city: Szczecin
country: Poland
facility: Pomorska Akademia Medyczna w Szczecinie, Samodzielny Publiczny Szpital Kliniczny Nr 2
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Clinical Oncological Dispensary
city: Kursk
country: Russian Federation
facility: Kursk Regional Oncologic Dispensary
city: Moscow
country: Russian Federation
facility: Moscow Clinical Scientific and Practical Center of Moscow Healthcare Department
city: Omsk
country: Russian Federation
facility: Omsk Region Clinical Oncologic Dispensary
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncological Dispensary
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint-Petersburg State Medical University
city: Saint Petersburg
country: Russian Federation
facility: State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
city: Saint-Petersburg
country: Russian Federation
facility: Saint Petersburg City Oncological Dispensary
city: Saransk
country: Russian Federation
facility: Republican oncological dispensary of Republic of Mordovia
city: Sochi
country: Russian Federation
facility: State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
city: Ufa
country: Russian Federation
facility: Republic Clinical Oncology Dispensary of the Ministry of Healthcare of Republic of Bashkortostan
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: Hospital Universitari Vall DHebron
city: Girona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: La Coruna
country: Spain
facility: Centro Oncologico Regional de Galicia
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz
city: Dnipropetrovsk
country: Ukraine
facility: Dnipropetrovsk City Multifield Clinical Hospital Number 4
city: Kyiv
country: Ukraine
facility: National Cancer Institute of the Ministry of Health of Ukraine
city: Lutsk
country: Ukraine
facility: Volyn Regional Oncology Dispensary
city: Lviv
country: Ukraine
facility: Lviv Regional Oncology Dispensary
city: Sumy
country: Ukraine
facility: Sumy Regional Oncology Center
city: Uzhgorod
country: Ukraine
facility: Zakarpattya Regional Clinical Oncological Dispensary
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust - Clinical Trial Pharmacy
state: England
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust
city: Coventry
country: United Kingdom
facility: University Hospital of Coventry and Warwickshire NHS Trust
city: Derby
country: United Kingdom
facility: Derby Teaching Hospital NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: London
country: United Kingdom
facility: University College London Hospitals
city: Middlesex
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle Hospitals NHS Foundation Trust
Study officials:
References:
citation: Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Poka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Oza AM. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Apr;23(4):465-478. doi: 10.1016/S1470-2045(22)00122-X. Epub 2022 Mar 14.