Study of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cy) in Patients With Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cyclophosphamide) in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03190265
• Other study ID #: J1790
• Secondary ID: IRB001373895P01C
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2017
• Est. completion date: August 23, 2023

Study information

• Verified date: August 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to study the safety and clinical activity of nivolumab and ipilimumab in combination with either sequential administration of CY/GVAX pancreas vaccine followed by CRS-207 (Arm A) or with administration of CRS-207 alone (Arm B) in patients with pancreatic cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: August 23, 2023
• Est. primary completion date: August 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years.

2. Have histologically or cytologically proven adenocarcinoma of the pancreas.

3. Have metastatic disease.

4. Have disease progression.

5. Patients with the presence of at least one measurable lesion.

6. Patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).

7. ECOG performance status 0 or 1

8. Life expectancy of greater than 3 months.

9. Patients must have adequate organ and marrow function defined by study-specified laboratory tests.

10. Must use acceptable form of birth control while on study.

11. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Known history or evidence of brain metastases.

2. Had surgery within the last 28 days

3. Had chemotherapy, radiation, or biological cancer therapy within the last 14 days

4. Have received a prophylactic vaccine within 14 days or received a live vaccine within 30 days of planned start of study therapy.

5. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2,or anti-CTLA4

6. Systemic steroids within the last 14 days

7. Use more than 2 g/day of acetaminophen.

8. Patients on immunosuppressive agents.

9. Patients receiving growth factors within the last 14 days

10. Known allergy to both penicillin and sulfa.

11. Severe hypersensitivity reaction to any monoclonal antibody.

12. Have artificial joints or implants that cannot be easily removed

13. Have any evidence of clinical or radiographic ascites.

14. Have significant and/or malignant pleural effusion

15. Have had a new pulmonary embolism, extremity deep venous thromboembolism, or portal vein thrombosis within 2 months of study treatment

16. Infection with HIV or hepatitis B or C at screening

17. Significant heart disease

18. Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures

19. Are pregnant or breastfeeding.

20. Have rapidly progressing disease

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Cyclophosphamide
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Cyclophosphamide (200 mg/m2) will be administered IV on day 1 of Cycles 1 and 2.
• Nivolumab
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Nivolumab (360 mg) will be administered IV on day 1 of Cycles 1-6.
• Ipilimumab
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Ipilimumab (1 mg/kg) will be administered IV on Day 1 of Cycles 1, 3, and 5.
• GVAX Pancreas Vaccine
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Vaccine will be administered on Day 2 of Cycles 1 and 2.
• CRS-207
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 109 CFU) will be administered IV on Day 2 of Cycles 3-6.
• CRS-207
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 (1 × 109 CFU) will be administered IV on Day 2 of Cycles 1-6.

Locations

Country	Name	City	State
United States	Johns Hopkins SKCCC	Baltimore	Maryland

Sponsors (4)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Aduro Biotech, Inc., Bristol-Myers Squibb, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)	Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.	18 months
Secondary	Number of Participants Experiencing Grade 3 or Above Study Drug-related Adverse Events (AEs)	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject. Laboratory abnormalities that were asymptomatic and not clinically significant were excluded.	21 months