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

Platinum-resistant Ovarian Cancer Clinical Trial

— SEASCAPE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02575807
• Other study ID #: ADU-CL-11
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 8, 2016
• Est. completion date: May 8, 2018

Study information

• Verified date: April 2019
• Source: Aduro Biotech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: May 8, 2018
• Est. primary completion date: April 26, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms
• Peritoneal Neoplasms
• Platinum-resistant Fallopian Cancer
• Platinum-resistant Ovarian Cancer
• Platinum-resistant Peritoneal Cancer

Intervention

Biological:
• CRS-207
via IV infusion

Drug:
• Epacadostat
PO BID

Biological:
• Pembrolizumab
via IV infusion

Locations

Country	Name	City	State
Canada	CHUM - Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Florida	Gainesville	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Scottsdale Healthcare Hospitals DBA HonorHealth	Scottsdale	Arizona
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Aduro Biotech, Inc.	Incyte Corporation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT)	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.	Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).
Primary	Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher	Count of subjects in the Phase 1 cohorts with incidences of CTCAE Grade 3 or higher AEs.	Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.
Primary	Phase 2: Adverse Events (AEs)	Count of subjects in the Phase 2 cohorts with incidences of AEs.	Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.
Primary	Phase 2: Objective Response Rate (ORR)	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.	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.
Primary	Phase 2: Progression Free Survival (PFS)	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.	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.
Secondary	Phase 1: Objective Response Rate (ORR) by mRECIST	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.	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.
Secondary	Phase 1: Progression Free Survival (PFS)	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.	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
Secondary	Disease Control Rate (DCR)	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.	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.
Secondary	Duration of Response (DOR)	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.	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.
Secondary	Overall Survival (OS)	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.	OS was assessed from the first dose of study treatment until death or study termination, whichever comes first, assessed up to 100 weeks.