Pancreatic Cancer
Conditions
Keywords
Adenocarcinoma, Cyclophosphamide, Immunotherapy, Adjuvant, Pancreatic tumor vaccine, GM-CSF, GVAX, Cancer vaccine
Brief summary
The purpose of this study is to evaluate the safety and feasibility of long term boost vaccination of a lethally irradiated, allogenic pancreatic tumor cell vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene (GVAX Pancreas Vaccine) alone or given in combination with either a single intravenous dose or daily metronomic oral doses of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of the pancreas.
Interventions
DRUGCyclophosphamide
Cohort 1 (J0810 Arm B), Cohort 3, Cohort 4, and Cohort 5 patients will receive 200mg/m\^2 CY administered IV on day 0 of each Cycle (every 6 months). Cohort 2 patients will receive 200mg/m\^2 CY administered IV on Day 0 of the first 3 cycles (every 28 days) and Day 0 of subsequent Cycles (every 6 months).
Cohort 1 patients (J0810 Arm C) will receive 50mg oral CY once a day starting 28 days prior to GVAX and for 28 days post-GVAX (every 6 months).
BIOLOGICALGVAX Pancreas Vaccine
Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months).
Sponsors
The Skip Viragh Foundation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has a history of surgically resected and pathologically proved AJCC stage I or stage II adenocarcinoma of the head, neck, or uncinate of the pancreas. 2. Cohorts 1, 3, 4 and 5: Have been a participant in Hopkins IRB protocol J0810, J1568, J15237 or J1766. 3. Cohort 2: Have never received any type of pancreatic cancer vaccine/immunotherapy, had the Whipple surgery within 18 months and completed the planned adjuvant chemotherapy and/or chemoradiation. 4. Cohorts 1, 3, 4 and 5: Received the last irradiated GM-CSF transfected allogeneic pancreatic cell lines Panc 10.05 and Panc 6.03 at least 6-12 months prior. 5. Has received the last anti-cancer therapy at least 28 days ago. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Has provided informed consent. 8. Has adequate hematologic function.(Hemoglobin ≥ 9 g/dL ANC ≥ 1500/mm3 Platelets ≥ 100,000 K/ mm3). 9. Has adequate renal function (Serum creatinine ≤ 2 mg/dL). 10. Has adequate hepatic function. (Bilirubin ≤ 2.0 mg/dl, unless known Gilbert's Syndrome; AST, ALT and amylase ≤ 2x upper limit of normal, Alk Phos ≤ 5x upper limit of normal). 11. Agree to use adequate birth control, if of childbearing potential.
Exclusion criteria
1. Has radiographic evidence of pancreatic cancer recurrence. 2. Has any documented history of autoimmune diseases including systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis,or vasculitis. 3. Has any uncontrolled medical problems. 4. Has had systemic steroid therapy within 28 days before vaccine administration. 5. Has an anticipated need for systemic steroid therapy within 28 days after vaccine administration. 6. Has any evidence of active infections. 7. Is pregnant. 8. Has a history of another cancer (other than pancreatic cancer) or myeloproliferative disorders in the past five years except for treated non-melanoma skin cancer, superficial bladder cancer, or carcinoma in-situ of the cervix. 9. Has a history of noncompliance during previous vaccination cycles with study treatment and/or monitoring which is concerning for continued noncompliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 121 Months | Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0 |
| Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 121 months | Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | 131 months | DFS was measured as the time from date of surgery until pancreatic cancer recurrence or death. Disease status was monitored by radiologic scans done per standard of care. DFS was censored on the date of last radiologic scan for subjects without documentation of cancer recurrence or death at the time of analysis. Estimation based on the Kaplan-Meier curve. |
| Overall Survival (OS) | 174 Months | OS was measured as the amount of time from date of surgery until death or end of follow-up. OS was censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis. Estimation based on the Kaplan-Meier curve. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (J0810 Arm A) Patients coming from J0810 (NCT00727441) Patients receive GVAX
GVAX Pancreas Vaccine: Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months). | 8 |
| Cohort 1 (J0810 Arm B) Patients coming from J0810 (NCT00727441) Patients receive IV CY and GVAX
Cyclophosphamide: Cohort 1 (J0810 Arm B), Cohort 3, Cohort 4, and Cohort 5 patients will receive 200mg/m\^2 CY administered IV on day 0 of each Cycle (every 6 months). Cohort 2 patients will receive 200mg/m\^2 CY administered IV on Day 0 of the first 3 cycles (every 28 days) and Day 0 of subsequent Cycles (every 6 months).
GVAX Pancreas Vaccine: Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months). | 3 |
| Cohort 1 (J0810 Arm C) Patients coming from J0810 (NCT00727441) Patients receive oral CY and GVAX
Cyclophosphamide Pill: Cohort 1 patients (J0810 Arm C) will receive 50mg oral CY once a day starting 28 days prior to GVAX and for 28 days post-GVAX (every 6 months).
GVAX Pancreas Vaccine: Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months). | 2 |
| Cohort 2 (Vaccine Naive) Patients receive IV CY and GVAX
Cyclophosphamide: Cohort 1 (J0810 Arm B), Cohort 3, Cohort 4, and Cohort 5 patients will receive 200mg/m\^2 CY administered IV on day 0 of each Cycle (every 6 months). Cohort 2 patients will receive 200mg/m\^2 CY administered IV on Day 0 of the first 3 cycles (every 28 days) and Day 0 of subsequent Cycles (every 6 months).
GVAX Pancreas Vaccine: Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months). | 52 |
| Cohort 3 (J1568) Patients coming from J1568 (NCT02451982) Patients receive IV CY and GVAX
Cyclophosphamide: Cohort 1 (J0810 Arm B), Cohort 3, Cohort 4, and Cohort 5 patients will receive 200mg/m\^2 CY administered IV on day 0 of each Cycle (every 6 months). Cohort 2 patients will receive 200mg/m\^2 CY administered IV on Day 0 of the first 3 cycles (every 28 days) and Day 0 of subsequent Cycles (every 6 months).
GVAX Pancreas Vaccine: Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months). | 6 |
| Cohort 4 (J15237) Patients coming from J15237 (NCT02648282) Patients receive IV CY and GVAX
Cyclophosphamide: Cohort 1 (J0810 Arm B), Cohort 3, Cohort 4, and Cohort 5 patients will receive 200mg/m\^2 CY administered IV on day 0 of each Cycle (every 6 months). Cohort 2 patients will receive 200mg/m\^2 CY administered IV on Day 0 of the first 3 cycles (every 28 days) and Day 0 of subsequent Cycles (every 6 months).
GVAX Pancreas Vaccine: Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months). | 0 |
| Cohort 5 (J1766) Patients coming from J1766 (NCT03153410) Patients receive IV CY and GVAX
Cyclophosphamide: Cohort 1 (J0810 Arm B), Cohort 3, Cohort 4, and Cohort 5 patients will receive 200mg/m\^2 CY administered IV on day 0 of each Cycle (every 6 months). Cohort 2 patients will receive 200mg/m\^2 CY administered IV on Day 0 of the first 3 cycles (every 28 days) and Day 0 of subsequent Cycles (every 6 months).
GVAX Pancreas Vaccine: Cohort 1, 3, 4, and 5 patients will receive GVAX on day 1 of each Cycle (every 6 months). Cohort 2 patients will receive GVAX on Day 1 of the first 3 cycles (every 28 days) and Day 1 of subsequent Cycles (every 6 months). | 0 |
| Total | 71 |
Baseline characteristics
| Characteristic | Cohort 2 (Vaccine Naive) | Cohort 4 (J15237) | Cohort 5 (J1766) | Total | Cohort 1 (J0810 Arm A) | Cohort 1 (J0810 Arm B) | Cohort 1 (J0810 Arm C) | Cohort 3 (J1568) |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 0 Participants | 0 Participants | 26 Participants | 3 Participants | 0 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 0 Participants | 0 Participants | 45 Participants | 5 Participants | 3 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 52 Participants | 0 Participants | 0 Participants | 70 Participants | 7 Participants | 3 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 24 Participants | 0 Participants | 0 Participants | 34 Participants | 3 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 28 Participants | 0 Participants | 0 Participants | 37 Participants | 5 Participants | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 8 | 3 / 3 | 1 / 2 | 37 / 52 | 3 / 6 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 7 / 8 | 3 / 3 | 2 / 2 | 52 / 52 | 4 / 6 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 1 / 8 | 1 / 3 | 0 / 2 | 8 / 52 | 0 / 6 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation
Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0
Time frame: 121 Months
Population: No patients were enrolled into Cohort 4 or Cohort 5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (J0810 Arm A) | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
| Cohort 1 (J0810 Arm B) | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
| Cohort 1 (J0810 Arm C) | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
| Cohort 2 (Vaccine Naive) | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 3 Participants |
| Cohort 3 (J1568) | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
| Cohort 4 (J15237) | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
| Cohort 5 (J1766) | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |
Primary
Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs)
Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0
Time frame: 121 months
Population: No patients were enrolled into Cohort 4 or Cohort 5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 (J0810 Arm A) | Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 1 Participants |
| Cohort 1 (J0810 Arm B) | Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 0 Participants |
| Cohort 1 (J0810 Arm C) | Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 0 Participants |
| Cohort 2 (Vaccine Naive) | Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 7 Participants |
| Cohort 3 (J1568) | Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 0 Participants |
| Cohort 4 (J15237) | Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 0 Participants |
| Cohort 5 (J1766) | Number of Participants Experiencing Grade 3 or Above Drug-Related Adverse Events (AEs) | 0 Participants |
Secondary
Disease Free Survival (DFS)
DFS was measured as the time from date of surgery until pancreatic cancer recurrence or death. Disease status was monitored by radiologic scans done per standard of care. DFS was censored on the date of last radiologic scan for subjects without documentation of cancer recurrence or death at the time of analysis. Estimation based on the Kaplan-Meier curve.
Time frame: 131 months
Secondary
Overall Survival (OS)
OS was measured as the amount of time from date of surgery until death or end of follow-up. OS was censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis. Estimation based on the Kaplan-Meier curve.
Time frame: 174 Months