Study With CY, Pembrolizumab, GVAX Pancreas Vaccine, and SBRT in Patients With Locally Advanced Pancreatic Cancer
Primary Purpose
Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
GVAX Pancreatic Cancer Vaccine
Pembrolizumab
SBRT
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring vaccine, immunotherapy, antibody, PD-1, radiation
Eligibility Criteria
Inclusion Criteria:
- locally advanced pancreatic adenocarcinoma
- Patients must have received mFOLFIRINOX or Gemcitabine/ Abraxane based chemotherapy for 4 cycles with last dose of therapy between 2-5 weeks of study enrollment.
- Age >18 years
- No metastatic disease
- ECOG Performance Status of 0 to 1
- Adequate organ function as defined by study-specified laboratory tests
- Patients must be able to have fiducials placed for SBRT
- Must use acceptable form of birth control through the study
- Signed informed consent form
- Willing and able to comply with study procedures
Exclusion Criteria:
- Patients who have been off of mFOLFIRINOX or gemcitabine/abraxane therapy for more than 49 days
- Patients who have had more than one line of chemotherapy
- Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements
- Patient who have had prior treatment with IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
- Patients receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days prior to first dose of study drug
- Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 14 days of study drug administration
- Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematous (SLE) autoimmune vasculitis, CNS or motor neuropathy considered to be of autoimmune origin.
- Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
- Patients with evidence of interstitial lung disease
- Patients on home oxygen
- Patients with oxygen saturation of <92% on room air by pulse oximetry
- Pregnant or lactating
- Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
Sites / Locations
- The Sidney Kimmel Comprehensive Cancer at Johns Hopkins
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cyclophosphamide, Pembrolizumab, GVAX Pancreas Vaccine, SBRT
Arm Description
Outcomes
Primary Outcome Measures
Distant Metastasis Free Survival (DMFS)
DMFS is defined as the duration of time from start of treatment to identification of distant metastases on imaging or death, whichever occurs first. Estimation based on the Kaplan-Meier curve.
Secondary Outcome Measures
Number of Participants Experiencing a Grade 3 or Above Treatment Related Toxicities
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Full Information
NCT ID
NCT02648282
First Posted
January 5, 2016
Last Updated
February 1, 2023
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02648282
Brief Title
Study With CY, Pembrolizumab, GVAX Pancreas Vaccine, and SBRT in Patients With Locally Advanced Pancreatic Cancer
Official Title
A Phase II Study of GM-CSF Secreting Allogeneic Pancreatic Cancer Vaccine in Combination With PD-1 Blockade Antibody (Pembrolizumab) and Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients With Locally Advanced Adenocarcinoma of the Pancreas
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
July 18, 2016 (Actual)
Primary Completion Date
June 1, 2022 (Actual)
Study Completion Date
June 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will be looking at whether combining cyclophosphamide, pembrolizumab (an antibody that blocks negative signals to T cells), GVAX (pancreatic cancer vaccine), and SBRT (focused radiation) is effective (anti-tumor activity) and safe in patients with locally advanced pancreatic cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
vaccine, immunotherapy, antibody, PD-1, radiation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cyclophosphamide, Pembrolizumab, GVAX Pancreas Vaccine, SBRT
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan, CY
Intervention Description
200 mg/m2 is to be administered as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg/m2 as a 30 minute IV infusion one day prior to GVAX Pancreas Vaccine every 6 months for an additional 4 doses.
Intervention Type
Drug
Intervention Name(s)
GVAX Pancreatic Cancer Vaccine
Other Intervention Name(s)
Pancreas cancer vaccine, Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo
Intervention Description
2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells is to be administered one day after CY and pembrolizumab for a total of 8 doses. In the extended treatment phase, eligible patients may receive 2.5E8 cells of each cell line (Panc 6.03/Panc 10.05) for a total of 5E8 cells administered one day after CY every 6 months for an additional 4 doses.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475, KEYTRUDA
Intervention Description
200 mg will be administered as a 30 minute IV infusion one day prior to the GVAX pancreas vaccine every 21 days for a total of 8 doses. In the extended treatment phase, eligible patients may receive 200 mg as a 30 minute IV infusion every 21 days for an additional 9 doses.
Intervention Type
Radiation
Intervention Name(s)
SBRT
Other Intervention Name(s)
Stereotactic Body Radiation Therapy
Intervention Description
Patients will receive SBRT (6.6 Gy for 5 days) with the second dose of combined immunotherapy (CY/Pembrolizumab/GVAX Pancreas Vaccine).
Primary Outcome Measure Information:
Title
Distant Metastasis Free Survival (DMFS)
Description
DMFS is defined as the duration of time from start of treatment to identification of distant metastases on imaging or death, whichever occurs first. Estimation based on the Kaplan-Meier curve.
Time Frame
62 months
Secondary Outcome Measure Information:
Title
Number of Participants Experiencing a Grade 3 or Above Treatment Related Toxicities
Description
When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
Time Frame
41 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Locally advanced pancreatic adenocarcinoma
Patients must have received mFOLFIRINOX or Gemcitabine/ Abraxane based chemotherapy for 4 cycles with last dose of therapy between 2-5 weeks of study enrollment.
Age >18 years
No metastatic disease
ECOG Performance Status of 0 to 1
Adequate organ function as defined by study-specified laboratory tests
Patients must be able to have fiducials placed for SBRT
Must use acceptable form of birth control through the study
Signed informed consent form
Willing and able to comply with study procedures
Exclusion Criteria:
Patients who have been off of mFOLFIRINOX or gemcitabine/abraxane therapy for more than 49 days
Patients who have had more than one line of chemotherapy
Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements
Patient who have had prior treatment with IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
Patients receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days prior to first dose of study drug
Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 14 days of study drug administration
Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematous (SLE) autoimmune vasculitis, CNS or motor neuropathy considered to be of autoimmune origin.
Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
Patients with evidence of interstitial lung disease
Patients on home oxygen
Patients with oxygen saturation of <92% on room air by pulse oximetry
Pregnant or lactating
Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Zheng, MD, PhD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Sidney Kimmel Comprehensive Cancer at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Study With CY, Pembrolizumab, GVAX Pancreas Vaccine, and SBRT in Patients With Locally Advanced Pancreatic Cancer
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