Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01891344
Other study ID # CO-338-017
Secondary ID 2013-000517-20
Status Completed
Phase Phase 2
First received
Last updated
Start date October 30, 2013
Est. completion date September 28, 2021

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

The purpose of this study is to determine which patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib.


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. Clinical data with PARP inhibitors indicate there is an ovarian cancer patient population beyond just those with germline BRCA (gBRCA) mutations that may benefit from treatment with a PARP inhibitor. This study will define a molecular signature of HRD in ovarian cancer that correlates with response to rucaparib and enables selection of appropriate ovarian cancer patients for treatment with rucaparib. The HRD signature will be based on an association between the extent of genomic scarring (a downstream consequence of HRD) in a patient's tumor and observed clinical benefit from rucaparib treatment. Genomic scarring can be assessed by quantifying the extent of loss of heterozygosity across the tumor genome (tumor genomic LOH). One of the main advantages of detecting tumor genomic LOH is that it can identify HRD tumors regardless of the underlying mechanisms, which include both known (i.e., BRCA mutations) and unknown genetic and other mechanisms. Once determined, this signature will be prospectively applied to ARIEL2 PART 2 and ARIEL3. This Phase 2 study (ARIEL2) will also compare archival versus recently collected tumor tissue in order to validate the use of archival tumor tissue for assessment of HRD status in ARIEL3. This study will include 2 parts: PART 1 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received ≥1 prior platinum-based regimen and had platinum-sensitive disease PART 2 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens


Recruitment information / eligibility

Status Completed
Enrollment 491
Est. completion date September 28, 2021
Est. primary completion date November 5, 2019
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility The following eligibility criteria pertain to patients enrolling into PART 2 of the study: Inclusion: - 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 at least 3 prior chemotherapy regimens. Non-chemotherapy regimens and maintenance therapies administered as single agent treatment will not count as a chemotherapy regimen - Relapsed/progressive disease as confirmed by CT scan - Have biopsiable and measurable disease. Note: biopsy is optional for patients known to harbor a deleterious gBRCA mutation - Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses Exclusion: - 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 - Hospitalization for bowel obstruction within 3 months prior to enrollment

Study Design


Intervention

Drug:
Oral rucaparib
600 mg BID

Locations

Country Name City State
Australia Flinders Cancer Clinic - Flinders Medical Centre (FMC) Bedford Park South Australia
Australia Mercy Hospital for Women Heidelberg Victoria
Australia Royal Brisbane & Women's Hospital Herston Queensland
Australia Charles Gairdner Hospital Nedlands Western Australia
Australia Royal Melbourne Hospital Parkville Victoria
Australia Royal North Shore Hospital Saint Leonards New South Wales
Australia Prince of Wales Hospital Sydney New South Wales
Australia Crown Princess Mary Cancer Centre (Westmead Hospital) Westmead Wentworthville
Canada Tom Baker Cancer Centre Calgary Alberta
Canada Cross Cancer Centre Edmonton Alberta
Canada British Columbia Cancer Agency Kelowna British Columbia
Canada London Regional Cancer Centre London Ontario
Canada Centre Hospitalier de L'Universite de Montreal Montreal Quebec
Canada Jewish General Hospital Montreal Quebec
Canada Ottawa Hospital Cancer Centre Ottawa Ontario
Canada CHU de Québec - Université Laval Québec
Canada BC Cancer Agency - Fraser Valley Centre Surrey British Columbia
Canada Princess Margaret Cancer Centre Toronto Ontario
Canada Vancouver Cancer Centre, British Columbia Cancer Agency (BCCA) Vancouver British Columbia
France Institut Bergonie Bordeaux Aquitaine
France Centre Leon Berard Lyon Rhone-Alpes
France Centre Catherine de Sienne Nantes Pays De La Loire
France Hôpital Européen Georges-Pompidou Paris Ile-de-France
France Hopital Tenon Paris Ile-de-France
France Centre Hospitalier Lyon Sud Pierre-Benite Rhone-Alpes
France Institut Claudius Regaud Toulouse Midi-Pyrenees
France Institut de cancerologie Gustave Roussy Villejuif Ile-de-France
Spain Hospital Vall d'Hebron Barcelona
Spain Hospital Clinico Universitario de Valencia Valencia
Spain Instituto Valencia de Oncologia Valencia
United Kingdom Addenbrooke's Hospital Cambridge
United Kingdom Beatson West of Scotland Cancer Centre Glasgow Scotland
United Kingdom St James University Hospital Leeds West Yorkshire
United Kingdom Imperial College Healthcare NHS Trust - Hammersmith Hospital London
United Kingdom Royal Marsden NHS Foundation Trust 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 Royal Marsden Sutton Hospital Sutton Surrey
United States Women's Cancer Care Associates Albany New York
United States Providence Alaska Medical Center Anchorage Alaska
United States Hope - A Woman's Cancer Institute Asheville North Carolina
United States Johns Hopkins Kimmel Cancer Center Baltimore Maryland
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States University of Cincinnati Physicians Company Cincinnati Ohio
United States The Ohio State University Wexner Medical Center Columbus Ohio
United States Saint Jude Heritage Medical Center Fullerton California
United States Comprehensive Cancer Centers of Nevada Henderson Nevada
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States Mayo Clinic Jacksonville Jacksonville Florida
United States Horizon BioAdvance Lafayette Indiana
United States Altus Research Lake Worth Florida
United States Rocky Mountain Cancer Centers Lakewood Colorado
United States University of California Los Angeles Los Angeles California
United States Norton Cancer Institute Louisville Kentucky
United States University of Miami Hospital & Clinics Sylvester Comprehensive Cancer Center Miami Florida
United States Memorial Sloan-Kettering Cancer Center New York New York
United States New York University Langone Medical Center New York New York
United States University of Oklahoma Oklahoma City Oklahoma
United States Florida Hospital Cancer Institute Orlando Florida
United States UF Health Cancer Center Orlando Florida
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States University of Pennsylvania Philadelphia Pennsylvania
United States UPMC Cancer Center Pittsburgh Pennsylvania
United States Mayo Clinic Rochester Minnesota
United States Washington University School of Medicine Saint Louis Missouri
United States UC San Diego San Diego California
United States California Pacific Medical Center San Francisco California
United States University of California, San Francisco 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 Washington - Seattle Cancer Care Alliance Seattle Washington
United States Stanford University Stanford California
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,  Canada,  France,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study) The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator 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 measureable increase in a non-target lesion, or the appearance of new lesions. Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.
Primary Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. 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. Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.
Secondary Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study) The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.
Secondary Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a 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. A 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. Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.
Secondary Duration of Response Per RECIST v1.1 Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. 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. Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.
Secondary Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator 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 measureable increase in a non-target lesion, or the appearance of new lesions. Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.
Secondary Overall Survival (Part 2 of Study) Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive. All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.
Secondary Steady State Trough (Cmin) Level Rucaparib Concentrations Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available. Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks
See also
  Status Clinical Trial Phase
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Withdrawn NCT05201001 - APX005M in Patients With Recurrent Ovarian Cancer Phase 2
Completed NCT02963831 - A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies Phase 1/Phase 2
Not yet recruiting NCT06376253 - A Phase I Study of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers Phase 1
Recruiting NCT05489211 - Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03) Phase 2
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Active, not recruiting NCT03667716 - COM701 (an Inhibitor of PVRIG) in Subjects With Advanced Solid Tumors. Phase 1
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Recruiting NCT05156892 - Tamoxifen and SUBA-Itraconzole Combination Testing in Ovarian Cancer Phase 1
Suspended NCT02432378 - Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines Phase 1/Phase 2
Recruiting NCT04533763 - Living WELL: A Web-Based Program for Ovarian Cancer Survivors N/A
Active, not recruiting NCT03371693 - Cytoreductive Surgery(CRS) Plus Hyperthermic Intraperitoneal Chemotherapy(HIPEC) With Lobaplatin in Advanced and Recurrent Epithelial Ovarian Cancer Phase 3
Withdrawn NCT03032614 - Combination of Carboplatin, Eribulin and Veliparib in Stage IV Cancer Patients Phase 2
Completed NCT01936363 - Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer Phase 2
Completed NCT02019524 - Phase Ib Trial of Two Folate Binding Protein Peptide Vaccines (E39 and J65) in Breast and Ovarian Cancer Patients Phase 1
Terminated NCT00788125 - Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT05059522 - Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing Phase 3
Active, not recruiting NCT04383210 - Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors Phase 2
Terminated NCT04586335 - Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors. Phase 1
Terminated NCT03146663 - NUC-1031 in Patients With Platinum-Resistant Ovarian Cancer Phase 2

External Links