Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3) (ARIEL3)
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| ClinicalTrials.gov Identifier: NCT01968213 |
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Recruitment Status :
Completed
First Posted : October 23, 2013
Results First Posted : August 3, 2018
Last Update Posted : February 13, 2023
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Sponsor:
Clovis Oncology, Inc.
Collaborators:
Foundation Medicine
Myriad Genetics, Inc.
Information provided by (Responsible Party):
Clovis Oncology, Inc.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer | Drug: Rucaparib Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 564 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 ) |
| Actual Study Start Date : | April 7, 2014 |
| Actual Primary Completion Date : | April 1, 2017 |
| Actual Study Completion Date : | July 7, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ovarian cancer
MedlinePlus related topics:
Ovarian Cancer
Drug Information available for:
Rucaparib
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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.
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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.
Other Names:
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Placebo Comparator: 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.
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Drug: 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. |
Primary Outcome Measures :
- 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) [ Time Frame: 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. ]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).
Secondary Outcome Measures :
- Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS) [ Time Frame: 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. ]To evaluate PFS by RECIST v1.1, as assessed by independent radiology review (IRR).
- Overall Survival (OS) [ Time Frame: All patients were followed for survival up to approximately 8.2 years. ]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 to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18 [ Time Frame: 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. ]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.
- Time to an 8-point Decrease in the Total Score of the FOSI-18 [ Time Frame: 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. ]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.
- Individual Model Parameter Estimates of Rucaparib and Covariates Identification [ Time Frame: Study data collection occurred over approximately 7 months. ]Concentration summary statistics
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01968213
Locations
Show 96 study locations
Sponsors and Collaborators
Clovis Oncology, Inc.
Foundation Medicine
Myriad Genetics, Inc.
Investigators
| Study Director: | Heidi Giordano | Clovis Oncology, Inc. |
Study Documents (Full-Text)
Documents provided by Clovis Oncology, Inc.:
Documents provided by Clovis Oncology, Inc.:
Study Protocol [PDF] July 6, 2020
Statistical Analysis Plan [PDF] April 21, 2017
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Clovis Oncology, Inc. |
| ClinicalTrials.gov Identifier: | NCT01968213 |
| Other Study ID Numbers: |
CO-338-014 |
| First Posted: | October 23, 2013 Key Record Dates |
| Results First Posted: | August 3, 2018 |
| Last Update Posted: | February 13, 2023 |
| Last Verified: | January 2023 |
Keywords provided by Clovis Oncology, Inc.:
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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 |
Additional relevant MeSH terms:
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Ovarian Neoplasms Carcinoma, Ovarian Epithelial Fallopian Tube Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female |
Urogenital Neoplasms Genital Diseases Endocrine System Diseases Gonadal Disorders Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Fallopian Tube Diseases Rucaparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |