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Safety and Efficacy of CRS-207 With Epacadostat in Platinum Resistant Ovarian, Fallopian or Peritoneal Cancer (SEASCAPE)

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ClinicalTrials.gov Identifier: NCT02575807
Recruitment Status : Terminated (Study was stopped due to low enrollment and lack of clinical activity.)
First Posted : October 15, 2015
Results First Posted : April 4, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Aduro Biotech, Inc.

Tracking Information
First Submitted Date  ICMJE October 12, 2015
First Posted Date  ICMJE October 15, 2015
Results First Submitted Date  ICMJE December 14, 2018
Results First Posted Date  ICMJE April 4, 2019
Last Update Posted Date April 4, 2019
Actual Study Start Date  ICMJE March 8, 2016
Actual Primary Completion Date April 26, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • 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). ]
    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:
    • any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT observation period (Cycle 1) and is Grade 3 or higher according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4;
    • any use of systemic steroids; and/or
    • a study drug dose interruption lasting ≥ 7 days for an adverse event with an unclear relationship to study drug.
    Hematological DLTs are defined as:
    • Grade 4 neutropenia lasting >7 days;
    • Grade ≥3 febrile neutropenia;
    • Grade 4 anemia;
    • Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia lasting >7 days or associated with bleeding; and/or
    • Dose delay >7 days secondary to myelosuppression.
  • 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. ]
    Count of subjects in the Phase 1 cohorts with incidences of CTCAE Grade 3 or higher AEs.
  • 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. ]
    Count of subjects in the Phase 2 cohorts with incidences of AEs.
  • 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. ]
    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.
  • 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. ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
  • Part 1: Determine recommended Phase 2 dose of epacadostat in combination with CRS-207 [ Time Frame: 12 months from study start ]
  • Part 2: Number of subjects achieving overall response rate (ORR) when given CRS-207 with or without epacadostat [ Time Frame: 24 months from initiation of Part 2 ]
    Measured using modified Response Evaluation Criteria in Solid Tumors(mRECIST);
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • 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. ]
    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.
  • 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 ]
    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.
  • 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. ]
    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.
  • 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. ]
    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.
  • 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. ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of CRS-207 With Epacadostat in Platinum Resistant Ovarian, Fallopian or Peritoneal Cancer
Official Title  ICMJE 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
Brief Summary This 2-part, Phase 1/2 study will test investigational cancer drugs known as CRS-207, epacadostat (IDO), and pembrolizumab (pembro). The purpose of this study is to find out how safe it is to give the investigational drugs to women with platinum-resistant ovarian, fallopian tube, or peritoneal cancer and if it helps patients with these types of cancer live longer or can help shrink or slow the growth of cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Platinum-resistant Ovarian Cancer
  • Platinum-resistant Fallopian Cancer
  • Platinum-resistant Peritoneal Cancer
Intervention  ICMJE
  • Biological: CRS-207
    via IV infusion
    Other Name: Live, attenuated double-deleted Listeria monocytogenes (LADD)
  • Drug: Epacadostat
    PO BID
    Other Names:
    • INCB024360
    • IDO
  • Biological: Pembrolizumab
    via IV infusion
    Other Names:
    • Keytruda®
    • Pembro
Study Arms  ICMJE
  • 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).

    Intervention: Biological: CRS-207
  • Experimental: Phase 1: CRS-207/IDO 100 mg

    CRS-207 administered in 3-week cycles, IDO administered twice daily (BID).

    • CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle).
    • IDO (100 milligrams [mg]) administered by mouth (PO) BID, starting on Day 2 of the first CRS-207 treatment cycle.
    Interventions:
    • Biological: CRS-207
    • Drug: Epacadostat
  • Experimental: Phase 1: CRS-207/IDO 300 mg

    CRS-207 administered in 3-week cycles, IDO administered BID.

    • CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle).
    • IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
    Interventions:
    • Biological: CRS-207
    • Drug: Epacadostat
  • Experimental: Phase 2: CRS-207/Pembro/IDO

    CRS-207 and pembrolizumab (pembro) administered in 3-week cycles, IDO administered BID.

    • CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle).
    • Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
    • IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.
    Interventions:
    • Biological: CRS-207
    • Drug: Epacadostat
    • Biological: Pembrolizumab
  • Experimental: Phase 2: CRS-207/Pembro

    CRS-207 and pembro administered in 3-week cycles.

    • CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle).
    • Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
    Interventions:
    • Biological: CRS-207
    • Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 1, 2019)
35
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2015)
86
Actual Study Completion Date  ICMJE May 8, 2018
Actual Primary Completion Date April 26, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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).
  2. Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  3. Agree to provide core biopsies at baseline and at Cycle 2 Day 15
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Available archived tumor tissue for central analysis
  6. Adequate organ and marrow function

Exclusion Criteria

  1. Platinum-refractory disease (progression during the first platinum-based chemotherapy)
  2. Major surgical procedure within 4 weeks prior to Study Day 1
  3. Inaccessible tumors or for whom biopsy is contraindicated
  4. Clinically significant ascites
  5. Phase 2 only: Previous treatment with >3 chemotherapy regimens for locally advanced or metastatic disease
  6. Active bowel obstruction, or hospitalization for bowel obstruction within 2 months prior to screening
  7. Require parenteral nutrition
  8. Hospitalization within 2 weeks prior to screening
  9. Received any anticancer medication or therapy in the 21 days prior to study Day 1
  10. Prior monoclonal antibody treatment within 4 weeks before study Day 1
  11. History of listeriosis or previous treatment with a listeria-based immunotherapy
  12. Known allergy to both penicillin and sulfa antibiotics
  13. Any immunodeficiency disease or immune-compromised state
  14. 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
  15. Pregnant or breastfeeding
  16. Clinically significant heart disease
  17. Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
  18. History of any autoimmune disease which required systemic therapy in the past 2 years
  19. Diagnosed with another malignancy within the past 3 years
  20. Currently receiving therapy with a UDP-glucuronosyltransferase 1A9 inhibitor including diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
  21. Receiving monoamine oxidase inhibitor (MAOIs) or a drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
  22. Had prior serotonin syndrome
  23. Has implanted medical devices that pose high risks for colonization and cannot be easily removed
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02575807
Other Study ID Numbers  ICMJE ADU-CL-11
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Aduro Biotech, Inc.
Study Sponsor  ICMJE Aduro Biotech, Inc.
Collaborators  ICMJE Incyte Corporation
Investigators  ICMJE Not Provided
PRS Account Aduro Biotech, Inc.
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP