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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
First received
Last updated
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
Health authority
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.

Study Design


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.
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