A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2) (ARIEL2)
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| ClinicalTrials.gov Identifier: NCT01891344 |
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Recruitment Status :
Active, not recruiting
First Posted : July 3, 2013
Last Update Posted : May 8, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ovarian Cancer Epithelial Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer | Drug: Oral rucaparib | Phase 2 |
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 (currently enrolling): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 493 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2) |
| Actual Study Start Date : | October 30, 2013 |
| Actual Primary Completion Date : | November 5, 2019 |
| Estimated Study Completion Date : | October 31, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ovarian cancer
rucaparib
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Drug: Oral rucaparib
600 mg BID
Other Names:
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- Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 1) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ]
- ORR by RECIST v1.1 (PART 2) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ]
- ORR by RECIST v1.1 (PART 1) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years (RECIST v1.1). ]
- Disease Progression (RECIST v1.1) as assessed by investigator, or death from any cause, in molecularly-defined subgroups identified by a prospectively defined HRD signature (PART 2) [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ]
- ORR by RECIST v1.1 and GCIG CA-125 criteria [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ]
- Duration of response per RECIST v1.1 [ Time Frame: Screening; at the end of every 8 weeks (±4 days) of treatment; at disease progression; study data collection expected to last for ~2 years ]
- Incidence of adverse events, clinical laboratory abnormalities, and dose modifications [ Time Frame: Every day starting with signing of consent until 28 days after discontinuation of treatment; study data collection expected to last for ~2 years ]
- Trough (Cmin) level rucaparib concentrations [ Time Frame: 2 weeks, 1 month, 2 months and 3 months after 1st dose ]
- Overall Survival (PART 2) [ Time Frame: study data collection expected to last for ~2 years ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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
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): NCT01891344
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Clovis Oncology, Inc. |
| ClinicalTrials.gov Identifier: | NCT01891344 |
| Other Study ID Numbers: |
CO-338-017 |
| First Posted: | July 3, 2013 Key Record Dates |
| Last Update Posted: | May 8, 2020 |
| Last Verified: | May 2020 |
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ovarian cancer fallopian tube cancer primary peritoneal cancer peritoneal cancer platinum sensitive relapsed disease PARP Inhibitor rucaparib homologous recombination homologous recombination deficiency genomic scarring loss of heterozygosity 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 ARIEL2 ARIEL 2 ARIEL3 ARIEL 3 |
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Ovarian Neoplasms Carcinoma, Ovarian Epithelial Fallopian Tube Neoplasms Peritoneal Neoplasms Hypersensitivity Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders |
Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Fallopian Tube Diseases Immune System Diseases Abdominal Neoplasms Digestive System Neoplasms Digestive System Diseases Peritoneal Diseases Rucaparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |