- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02575807
Safety and Efficacy of CRS-207 With Epacadostat in Platinum Resistant Ovarian, Fallopian or Peritoneal Cancer (SEASCAPE)
A Phase 1/2, Open-Label Safety and Efficacy Evaluation of CRS-207 in Combination With Epacadostat in Adults With Platinum-Resistant Ovarian, Fallopian, or Peritoneal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Cancer Centre
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Quebec
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Montréal, Quebec, Canada, H2X 0A9
- CHUM - Centre Hospitalier de l'Universite de Montreal
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Arizona
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Scottsdale, Arizona, United States, 85258
- Scottsdale Healthcare Hospitals DBA HonorHealth
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California
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Stanford, California, United States, 94305
- Stanford Cancer Center
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Florida
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Gainesville, Florida, United States, 32610
- University of Florida
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Health System
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Virginia
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Charlottesville, Virginia, United States, 22903
- University of Virginia Health System
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Washington
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Seattle, Washington, United States, 98101
- Virginia Mason Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically-confirmed disease
- Phase 1: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of platinum-based chemotherapy).
- Phase 2: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of a minimum of 4 platinum therapy cycles).
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Agree to provide core biopsies at baseline and at Cycle 2 Day 15
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Available archived tumor tissue for central analysis
- Adequate organ and marrow function
Exclusion Criteria
- Platinum-refractory disease (progression during the first platinum-based chemotherapy)
- Major surgical procedure within 4 weeks prior to Study Day 1
- Inaccessible tumors or for whom biopsy is contraindicated
- Clinically significant ascites
- Phase 2 only: Previous treatment with >3 chemotherapy regimens for locally advanced or metastatic disease
- Active bowel obstruction, or hospitalization for bowel obstruction within 2 months prior to screening
- Require parenteral nutrition
- Hospitalization within 2 weeks prior to screening
- Received any anticancer medication or therapy in the 21 days prior to study Day 1
- Prior monoclonal antibody treatment within 4 weeks before study Day 1
- History of listeriosis or previous treatment with a listeria-based immunotherapy
- Known allergy to both penicillin and sulfa antibiotics
- Any immunodeficiency disease or immune-compromised state
- Received prior immune checkpoint inhibitors (e.g., anti-CTLA-4, anti-PD-1, anti PDL-1) and any other antibody or drug specifically targeting T-cell costimulation or an IDO inhibitor
- Pregnant or breastfeeding
- Clinically significant heart disease
- Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
- History of any autoimmune disease which required systemic therapy in the past 2 years
- Diagnosed with another malignancy within the past 3 years
- Currently receiving therapy with a UDP-glucuronosyltransferase 1A9 inhibitor including diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
- Receiving monoamine oxidase inhibitor (MAOIs) or a drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
- Had prior serotonin syndrome
- Has implanted medical devices that pose high risks for colonization and cannot be easily removed
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase 1: CRS-207
CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 colony forming units [CFU]) administered by intravenous (IV) infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle). |
via IV infusion
Other Names:
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Experimental: Phase 1: CRS-207/IDO 100 mg
CRS-207 administered in 3-week cycles, IDO administered twice daily (BID).
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via IV infusion
Other Names:
PO BID
Other Names:
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Experimental: Phase 1: CRS-207/IDO 300 mg
CRS-207 administered in 3-week cycles, IDO administered BID.
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via IV infusion
Other Names:
PO BID
Other Names:
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Experimental: Phase 2: CRS-207/Pembro/IDO
CRS-207 and pembrolizumab (pembro) administered in 3-week cycles, IDO administered BID.
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via IV infusion
Other Names:
PO BID
Other Names:
via IV infusion
Other Names:
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Experimental: Phase 2: CRS-207/Pembro
CRS-207 and pembro administered in 3-week cycles.
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via IV infusion
Other Names:
via IV infusion
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT)
Time Frame: Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).
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Count of subjects in the Phase 1 cohorts who reported a hematologic and/or non-hematologic DLT. Non-hematological DLTs are defined as follows, excluding the safety events specified for exemption in Section 5.3.1 of the study protocol:
Hematological DLTs are defined as:
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Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).
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Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher
Time Frame: Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.
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Count of subjects in the Phase 1 cohorts with incidences of CTCAE Grade 3 or higher AEs.
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Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.
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Phase 2: Adverse Events (AEs)
Time Frame: Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.
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Count of subjects in the Phase 2 cohorts with incidences of AEs.
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Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.
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Phase 2: Objective Response Rate (ORR)
Time Frame: BOR was assessed from the first dose of study treatment until documented disease progression, initiation of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 20 weeks.
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ORR was evaluated for Phase 2 subjects based upon the best overall response (BOR) for individual study subjects.
BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE).
The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP).
Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.
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BOR was assessed from the first dose of study treatment until documented disease progression, initiation of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 20 weeks.
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Phase 2: Progression Free Survival (PFS)
Time Frame: Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 20 weeks.
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Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs).
PD is determined by mRECIST.
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Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 20 weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Objective Response Rate (ORR) by mRECIST
Time Frame: BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 100 weeks.
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ORR was evaluated for Phase 1 subjects based upon the best overall response (BOR) for individual study subjects.
BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST), RECIST v1.1, and GCIG CA-125 criteria and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE).
The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP).
Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.
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BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 100 weeks.
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Phase 1: Progression Free Survival (PFS)
Time Frame: Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 100 weeks
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Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death due to any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs).
PD is determined by mRECIST, RECIST v1.1, and GCIG CA-125.
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Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 100 weeks
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Disease Control Rate (DCR)
Time Frame: BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 100 weeks.
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The protocol-specified DCR was defined as the percentage of evaluable subjects with a BOR of CR or PR, or SD as determined by mRECIST, RECIST v1.1, and GCIG CA-125 criteria.
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BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 100 weeks.
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Duration of Response (DOR)
Time Frame: Subjects followed for disease progression from date of CR or PR designation until documented disease progression or study termination, whichever comes first, assessed up to 100 weeks.
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Number of weeks from date of CR or PR designation until PD designation, as determined by mRECIST, RECIST v1.1 and GCIG CA-125 criteria.
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Subjects followed for disease progression from date of CR or PR designation until documented disease progression or study termination, whichever comes first, assessed up to 100 weeks.
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Overall Survival (OS)
Time Frame: OS was assessed from the first dose of study treatment until death or study termination, whichever comes first, assessed up to 100 weeks.
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Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF.
Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive.
For subjects lost to follow up, the last visit or last contact date where the subject is documented to be alive will be used to estimate last known date alive.
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OS was assessed from the first dose of study treatment until death or study termination, whichever comes first, assessed up to 100 weeks.
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Peritoneal Diseases
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Abdominal Neoplasms
- Ovarian Neoplasms
- Peritoneal Neoplasms
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Pembrolizumab
Other Study ID Numbers
- ADU-CL-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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