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ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

Primary Purpose

Ovarian Cancer, Epithelial Ovarian Cancer, Fallopian Tube Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Chemotherapy
Rucaparib
Sponsored by
pharmaand GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Rocky Mountain Cancer Center
  • Augusta University
  • Hospital Haroldo Juacaba Instituto do Cancer do Ceara
  • Instituto de Oncologia do Parana (IOP)
  • União Brasileira de Educação e Assistência / Hospital São Lucas da PUCRS
  • CEPON-Centro de pesquisas Oncologicas
  • Hospital do Cancer de Barretos
  • Instituto Nacional de Câncer Hospital do Câncer II
  • Hospital Pérola Byington - Centro de Referência da Saúde da Mulher
  • Hospital São Camilo
  • Tom Baker Cancer Center
  • The Ottawa Hospital - General Campus
  • Princess Margaret Hospital
  • Centre Hospitalier de L'Universite de Montreal (CHUM)
  • CIUSSS de l'Estrie CHUS
  • Masarykuv Onkologicky Ustav, Oddeleni komplexni klinicke onkologie
  • Fakultni Nemocnice v Motole
  • Fakultní Nemocnice Ostrava
  • Všeobecná Fakultní Nemocnice v Praze
  • Debreceni Egyetem Klinikai Központ
  • Országos Onkológiai Intézet
  • Carmel Medical Center
  • Edith Wolfson Medical Center
  • Hadassah Medical Organization
  • Rabin Medical Center
  • Chaim Sheba Medical Center
  • Tel Aviv Sourasky Medical Center, Oncology Dept.
  • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
  • Istituto per la Ricerca e la Cura del Cancro Istituto di Candiolo
  • AO per l'emergenza Cannizzaro
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Istituto Europeo di Oncologia
  • Azienda Ospedaliero-Universitaria Policlinico di Modena
  • Istituto Nazionale per lo studio e la cura dei tumori "Fondazione Pascale" Oncologia Medica
  • Fondazione Policlinico Universitario Agostino Gemelli
  • Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna Sp z o.o.
  • Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie
  • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
  • Wojewodzki Szpital Specjalistyczny w Olsztynie
  • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Pozna
  • Pomorska Akademia Medyczna w Szczecinie, Samodzielny Publiczny Szpital Kliniczny Nr 2
  • Arkhangelsk Clinical Oncological Dispensary
  • Kursk Regional Oncologic Dispensary
  • Moscow Clinical Scientific and Practical Center of Moscow Healthcare Department
  • Omsk Region Clinical Oncologic Dispensary
  • Pyatigorsk Oncological Dispensary
  • Ryazan Regional Clinical Oncology Dispensary
  • Pavlov First Saint-Petersburg State Medical University
  • State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
  • Saint Petersburg City Oncological Dispensary
  • Republican oncological dispensary of Republic of Mordovia
  • State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
  • Republic Clinical Oncology Dispensary of the Ministry of Healthcare of Republic of Bashkortostan
  • Hospital Duran i Reynals
  • Hospital Universitari Vall DHebron
  • Hospital Universitari de Girona Doctor Josep Trueta
  • Centro Oncologico Regional de Galicia
  • Hospital Clinico San Carlos
  • Hospital Universitario Ramón y Cajal
  • MD Anderson Cancer Center
  • Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz
  • Dnipropetrovsk City Multifield Clinical Hospital Number 4
  • National Cancer Institute of the Ministry of Health of Ukraine
  • Volyn Regional Oncology Dispensary
  • Lviv Regional Oncology Dispensary
  • Sumy Regional Oncology Center
  • Zakarpattya Regional Clinical Oncological Dispensary
  • The Christie NHS Foundation Trust - Clinical Trial Pharmacy
  • The Royal Marsden NHS Foundation Trust
  • Cambridge University Hospitals NHS Foundation Trust
  • Velindre NHS Trust
  • University Hospital of Coventry and Warwickshire NHS Trust
  • Derby Teaching Hospital NHS Foundation Trust
  • NHS Greater Glasgow and Clyde
  • University College London Hospitals
  • East and North Hertfordshire NHS Trust
  • Newcastle Hospitals NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rucaparib

Chemotherapy

Arm Description

Drug: Oral rucaparib 600 mg BID (twice a day) Other Names: CO-338 PF 01367338 AG 14699 Rubraca

Monotherapy platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision. Single agent paclitaxel will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.

Outcomes

Primary Outcome Measures

Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)
The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.
Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)
The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures

Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)
A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)
A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.
Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)
A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)
A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)
A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. 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.
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)
A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. 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.
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)
EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.
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)
EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.
Overall Survival (Efficacy Population)
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.
Overall Survival (ITT Population)
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.

Full Information

First Posted
July 22, 2016
Last Updated
June 7, 2023
Sponsor
pharmaand GmbH
Collaborators
Foundation Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT02855944
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
December 3, 2020 (Actual)
Study Completion Date
September 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
pharmaand GmbH
Collaborators
Foundation Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
349 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rucaparib
Arm Type
Experimental
Arm Description
Drug: Oral rucaparib 600 mg BID (twice a day) Other Names: CO-338 PF 01367338 AG 14699 Rubraca
Arm Title
Chemotherapy
Arm Type
Active Comparator
Arm Description
Monotherapy platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision. Single agent paclitaxel will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Other Intervention Name(s)
Cisplatin, carboplatin, carboplatin/paclitaxel, carboplatin/gemcitabine, paclitaxel
Intervention Description
Chemotherapy will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.
Intervention Type
Drug
Intervention Name(s)
Rucaparib
Other Intervention Name(s)
CO-338, AG 14699, PF 01367338, Rubraca
Intervention Description
Tablets of rucaparib, at a dose of 600 mg, will be taken orally twice a day
Primary Outcome Measure Information:
Title
Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)
Description
The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame
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.
Title
Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)
Description
The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame
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 Outcome Measure Information:
Title
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)
Description
A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.
Time Frame
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.
Title
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)
Description
A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.
Time Frame
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.
Title
Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)
Description
A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame
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.
Title
Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)
Description
A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame
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.
Title
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)
Description
A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. 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.
Time Frame
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.
Title
Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)
Description
A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. 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.
Time Frame
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.
Title
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)
Description
EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.
Time Frame
Baseline to the end of Cycle 6, or up to approximately 6 months
Title
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)
Description
EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.
Time Frame
Baseline to the end of Cycle 6, or up to approximately 6 months
Title
Overall Survival (Efficacy Population)
Description
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.
Time Frame
All patients were followed for survival up to approximately 3.5 years.
Title
Overall Survival (ITT Population)
Description
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.
Time Frame
All patients were followed for survival up to approximately 3.5 years.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Hospital Haroldo Juacaba Instituto do Cancer do Ceara
City
Fortaleza
State/Province
Ceara
Country
Brazil
Facility Name
Instituto de Oncologia do Parana (IOP)
City
Curitiba
State/Province
Parana
Country
Brazil
Facility Name
União Brasileira de Educação e Assistência / Hospital São Lucas da PUCRS
City
Porto Alegre
State/Province
RIO Grande DO SUL
Country
Brazil
Facility Name
CEPON-Centro de pesquisas Oncologicas
City
Florianópolis
State/Province
Santa Catarina
Country
Brazil
Facility Name
Hospital do Cancer de Barretos
City
Barretos
State/Province
SAO Paulo
Country
Brazil
Facility Name
Instituto Nacional de Câncer Hospital do Câncer II
City
Rio de Janeiro
Country
Brazil
Facility Name
Hospital Pérola Byington - Centro de Referência da Saúde da Mulher
City
Sao Paulo
Country
Brazil
Facility Name
Hospital São Camilo
City
Sao Paulo
Country
Brazil
Facility Name
Tom Baker Cancer Center
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
The Ottawa Hospital - General Campus
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Centre Hospitalier de L'Universite de Montreal (CHUM)
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
CIUSSS de l'Estrie CHUS
City
Sherbrooke
State/Province
Quebec
Country
Canada
Facility Name
Masarykuv Onkologicky Ustav, Oddeleni komplexni klinicke onkologie
City
Brno
State/Province
Jihormoravsky KRAJ
Country
Czechia
Facility Name
Fakultni Nemocnice v Motole
City
Praha 5
State/Province
Praha
Country
Czechia
Facility Name
Fakultní Nemocnice Ostrava
City
Ostrava
Country
Czechia
Facility Name
Všeobecná Fakultní Nemocnice v Praze
City
Praha
Country
Czechia
Facility Name
Debreceni Egyetem Klinikai Központ
City
Debrecen
State/Province
Hajdu-bihar
Country
Hungary
Facility Name
Országos Onkológiai Intézet
City
Budapest
Country
Hungary
Facility Name
Carmel Medical Center
City
Haifa
Country
Israel
Facility Name
Edith Wolfson Medical Center
City
Holon
Country
Israel
Facility Name
Hadassah Medical Organization
City
Jerusalem
Country
Israel
Facility Name
Rabin Medical Center
City
Petach-Tikva
Country
Israel
Facility Name
Chaim Sheba Medical Center
City
Ramat Gan
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center, Oncology Dept.
City
Tel Aviv
Country
Israel
Facility Name
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
City
Bologna
Country
Italy
Facility Name
Istituto per la Ricerca e la Cura del Cancro Istituto di Candiolo
City
Candiolo
Country
Italy
Facility Name
AO per l'emergenza Cannizzaro
City
Catania
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
Country
Italy
Facility Name
Istituto Europeo di Oncologia
City
Milano
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria Policlinico di Modena
City
Modena
Country
Italy
Facility Name
Istituto Nazionale per lo studio e la cura dei tumori "Fondazione Pascale" Oncologia Medica
City
Napoli
Country
Italy
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli
City
Roma
Country
Italy
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna Sp z o.o.
City
Grzybnica
State/Province
West Pomeranian Voivodeship
Country
Poland
Facility Name
Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie
City
Bialystok
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
City
Lublin
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny w Olsztynie
City
Olsztyn
Country
Poland
Facility Name
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Pozna
City
Poznan
Country
Poland
Facility Name
Pomorska Akademia Medyczna w Szczecinie, Samodzielny Publiczny Szpital Kliniczny Nr 2
City
Szczecin
Country
Poland
Facility Name
Arkhangelsk Clinical Oncological Dispensary
City
Arkhangelsk
Country
Russian Federation
Facility Name
Kursk Regional Oncologic Dispensary
City
Kursk
Country
Russian Federation
Facility Name
Moscow Clinical Scientific and Practical Center of Moscow Healthcare Department
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Omsk Region Clinical Oncologic Dispensary
City
Omsk
Country
Russian Federation
Facility Name
Pyatigorsk Oncological Dispensary
City
Pyatigorsk
Country
Russian Federation
Facility Name
Ryazan Regional Clinical Oncology Dispensary
City
Ryazan
Country
Russian Federation
Facility Name
Pavlov First Saint-Petersburg State Medical University
City
Saint Petersburg
Country
Russian Federation
Facility Name
State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
City
Saint Petersburg
Country
Russian Federation
Facility Name
Saint Petersburg City Oncological Dispensary
City
Saint-Petersburg
Country
Russian Federation
Facility Name
Republican oncological dispensary of Republic of Mordovia
City
Saransk
Country
Russian Federation
Facility Name
State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
City
Sochi
Country
Russian Federation
Facility Name
Republic Clinical Oncology Dispensary of the Ministry of Healthcare of Republic of Bashkortostan
City
Ufa
Country
Russian Federation
Facility Name
Hospital Duran i Reynals
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall DHebron
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta
City
Girona
Country
Spain
Facility Name
Centro Oncologico Regional de Galicia
City
La Coruna
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
MD Anderson Cancer Center
City
Madrid
Country
Spain
Facility Name
Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
Dnipropetrovsk City Multifield Clinical Hospital Number 4
City
Dnipropetrovsk
Country
Ukraine
Facility Name
National Cancer Institute of the Ministry of Health of Ukraine
City
Kyiv
Country
Ukraine
Facility Name
Volyn Regional Oncology Dispensary
City
Lutsk
Country
Ukraine
Facility Name
Lviv Regional Oncology Dispensary
City
Lviv
Country
Ukraine
Facility Name
Sumy Regional Oncology Center
City
Sumy
Country
Ukraine
Facility Name
Zakarpattya Regional Clinical Oncological Dispensary
City
Uzhgorod
Country
Ukraine
Facility Name
The Christie NHS Foundation Trust - Clinical Trial Pharmacy
City
Manchester
State/Province
England
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
Sutton
State/Province
Surrey
Country
United Kingdom
Facility Name
Cambridge University Hospitals NHS Foundation Trust
City
Cambridge
Country
United Kingdom
Facility Name
Velindre NHS Trust
City
Cardiff
Country
United Kingdom
Facility Name
University Hospital of Coventry and Warwickshire NHS Trust
City
Coventry
Country
United Kingdom
Facility Name
Derby Teaching Hospital NHS Foundation Trust
City
Derby
Country
United Kingdom
Facility Name
NHS Greater Glasgow and Clyde
City
Glasgow
Country
United Kingdom
Facility Name
University College London Hospitals
City
London
Country
United Kingdom
Facility Name
East and North Hertfordshire NHS Trust
City
Middlesex
Country
United Kingdom
Facility Name
Newcastle Hospitals NHS Foundation Trust
City
Newcastle upon Tyne
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35298906
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.
Results Reference
derived

Learn more about this trial

ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

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