Pancreatic Cancer
Conditions
Keywords
Neoadjuvant therapy, immunotherapy, Cytoxan, Cyclophosphamide, Pancreatic Vaccine, SBRT, GVAX, Nivolumab, borderline resectable, Radioimmunotherapy, Vaccine, Antibody, Anti-PD-1
Brief summary
The purpose of this study is to evaluate the safety and clinical activity of FOLFIRINOX along with a whole cell vaccine with immune modulating doses of cyclophosphamide and nivolumab combined with Stereotactic Body Radiation Therapy (SBRT) in patients with pancreatic cancer.
Interventions
DRUGCyclophosphamide
Cyclophosphamide 200 mg/m2 will be administered one day prior to vaccination (day 0). First dose will be given within 4 to 6 weeks after chemotherapy. 3 weeks after the first dose of immunotherapy the second dose will be given.
DRUGNivolumab
Nivolumab (240 mg) will be administered one day prior to vaccination. First dose will be given within 4 to 6 weeks after chemotherapy. 3 weeks after the first dose of immunotherapy the second dose will be given.
Vaccine will be administered one day after cyclophosphamide and nivolumab. 3 weeks after the first dose of immunotherapy the second dose will be given.
RADIATIONStereotactic Body Radiation (SBRT)
SBRT (6.6 Gy over 5 days) will be started during the second dose of immunotherapy (3 weeks after the first dose of immunotherapy).
Sponsors
Bristol-Myers Squibb
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically proven pancreatic cancer that is borderline resectable * No more than 1 month/cycle (28 days) of systemic therapy for pancreatic cancer * Age \>18 years old. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Patients must have adequate organ and marrow function defined by study-specified laboratory tests. * Woman of child bearing potential must have a negative pregnancy test. * Must use an acceptable form of birth control while on study. * Must be candidate for Stereotactic Body Radiation Therapy (SBRT) * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Had major surgery within the last 28 days * Had an investigational drug or device within the past 28 days * Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc) * Completed more than 1 month/cycle (28 days) of chemotherapy for pancreas cancer * Patient on an immunosuppressive systemic treatment, such as steroids, in the past 2 years. * Other cancer diagnosis requiring treatment within two years * History of allergic reactions related to the drugs (Nivolumab, Cyclophosphamide, GM-hetastarch, corn, dimethyl sulfoxide, fetal bovine serum, trypsin (porcine origin), yeast or any other component of the GVAX vaccine) in this study. * Patients receiving growth factors within the last 14 days. * Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, psychological, immune or other medical conditions. * Pregnant or breastfeeding. * Have known history of infection with HIV, hepatitis B, or hepatitis C. * Unwilling or unable to follow the study schedule for any reason. * Presence of tissue or organ allograft, regardless of need for immunosuppression (including corneal allograft) * Squamous pancreatic cancer or adenosquamous pancreatic cancer with malignant squamous cells \>30%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CD8+ T Cell Density in Tumor Tissue | evaluated at time of surgery, approximately 2 months from first dose of study drug | Mean CD8+ T cell density \[log(cells per mm\^2)\], found in resected surgical tissue by Immunohistochemistry (IHC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate at Surgical Resection | Assessed at time of surgical resection, approximately 2 months after first dose of study drug | Number of patients with a pathologic complete response (pCR) rate at surgical resection. A pCR is defined as no viable residual tumor remaining at the time of evaluation. |
Countries
United States
Participant flow
Pre-assignment details
Participants with borderline resectable pancreatic cancer were enrolled on the study prior to starting standard of care chemotherapy. After completing chemotherapy, participants were re-screened to determine if they were eligible to continue on the study and receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| CY, Nivolumab, GVAX, and SBRT Participants received a total of two cycles of Cylophosphamide (CY), Nivolumab, and GVAX Pancreas Vaccine, starting 4-6 weeks after completion of standard of care chemotherapy. Stereotactic Body Radiation Therapy (SBRT) was given over 5 days concurrently with the start of the second cycle. Patients were then evaluated for surgery, and if eligible, had their pancreas tumors resected.
Cyclophosphamide: 200 mg/m2 IV over 30 minutes on Day 1 of each 21-day cycle.
Nivolumab: 240 mg IV over 60 minutes on Day 1 of each 21-day cycle.
GVAX Pancreas Vaccine: 5x10\^8 cells, given as 6 intradermal injections (2 on each thigh and 2 on the non-dominant arm), given on Day 2 of each cycle.
Stereotactic Body Radiation (SBRT): 6.6 Gy over 5 days | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | disease progression during chemotherapy | 5 |
| Overall Study | no longer surgical candidate after chemotherapy | 2 |
| Overall Study | not eligible to start study drug after chemotherapy | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | CY, Nivolumab, GVAX, and SBRT |
|---|---|
| Age, Continuous | 62 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 0 | 16 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 1 | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 16 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
Primary
CD8+ T Cell Density in Tumor Tissue
Mean CD8+ T cell density \[log(cells per mm\^2)\], found in resected surgical tissue by Immunohistochemistry (IHC).
Time frame: evaluated at time of surgery, approximately 2 months from first dose of study drug
Population: Only participants who received study drug, completed surgical resection, and had sufficient tissue to perform IHC analysis. Of the 18 participants treated on study, 13 had sufficient tissue to perform CD8 analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CY, Nivolumab, GVAX, and SBRT | CD8+ T Cell Density in Tumor Tissue | 5.4 log (cells per mm^2) | Standard Deviation 0.8 |
Secondary
Pathologic Complete Response (pCR) Rate at Surgical Resection
Number of patients with a pathologic complete response (pCR) rate at surgical resection. A pCR is defined as no viable residual tumor remaining at the time of evaluation.
Time frame: Assessed at time of surgical resection, approximately 2 months after first dose of study drug
Population: Only participants who received study drug and completed surgical resection are included. Of the 18 participants treated on study, 14 completed surgical resection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CY, Nivolumab, GVAX, and SBRT | Pathologic Complete Response (pCR) Rate at Surgical Resection | 1 Participants |