A Trial of Boost Vaccinations of Pancreatic Tumor Cell Vaccine

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Recruiting

CT.gov ID

NCT01088789

Collaborator

The Skip Viragh Foundation (Other)

Enrollment

Location

Arms

155.4

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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 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 head, neck, tail or the uncinate process of the pancreas.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.	Phase 2

Detailed Description

Primary Objective:

To evaluate the safety and feasibility of long term boost vaccinations of a lethally irradiated, allogeneic pancreatic tumor cell vaccine transfected with the GM-CSF gene given alone or 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 head, neck, or uncinate process of the pancreas.

Secondary Objective:

To assess the effect of boost vaccinations and long-term treatment of immune modulating doses of cyclophosphamide on the number, repertoire and avidity of peripheral mesothelin-specific CD8+ T cells.
To estimate disease-free and overall survival of surgically resected pancreatic adenocarcinoma patients treated with vaccine boosts with or without low dose cyclophosphamide.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Safety and Feasibility Trial of Boost Vaccinations of a Lethally Irradiated, Allogeneic Pancreatic Tumor Cell Vaccine Transfected With the GM-CSF Gene

Actual Study Start Date :

Apr 20, 2010

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Cohort 1 Arm A: Vaccine only. Arm B receives vaccine as well as a single dose of intravenous cyclophosphamide. Arm C: In addition to Vaccine Cohort 3 receives a daily dose of metronomic cyclophosphamide orally. Only patients from the J0810 study are eligible. Closed to enrollment.	Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine. A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months. Other Names: Cyclophosphamide
Other: Cohort 2 Cohort 2 receives vaccine as well as a single dose of intravenous cyclophosphamide. Vaccine-naïve cohort. Closed to enrollment.	Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine. A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months. Other Names: Cyclophosphamide
Other: Cohort 3 Cohort 3 receives vaccine as well as a single dose of intravenous cyclophosphamide. Only participants from J1568 study are eligible.	Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine. A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months. Other Names: Cyclophosphamide
Other: Cohort 4 Cohort 4 receives vaccine as well as a single dose of intravenous cyclophosphamide. Only participants from J15237 study are eligible.	Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine. A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months. Other Names: Cyclophosphamide
Other: Cohort 5 Cohort 5 receives vaccine as well as a single dose of intravenous cyclophosphamide. Only participants from J1766 study are eligible.	Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine. A pancreatic vaccine secreting a granulocyte-macrophage colony-stimulating factor(GM-CSF). The vaccine consists of equal numbers of pancreatic cancer cells (Panc 6.03)and (Panc. 10.05) into a single vaccine. The vaccine is administered every 6 months. Other Names: Cyclophosphamide

Outcome Measures

Primary Outcome Measures

Disease free overall survival. [total of 13 years with 6 months between vaccines.]
Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Cohorts 1, 3, 4 and 5: Have been a participant in Hopkins IRB protocol J0810, J1568, J15237 or J1766.
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.
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.
Has received the last anti-cancer therapy at least 28 days ago.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Has provided informed consent.
Has adequate hematologic function.(Hemoglobin ≥ 9 g/dL ANC ≥ 1500/mm3 Platelets ≥ 100,000 K/ mm3).
Has adequate renal function (Serum creatinine ≤ 2 mg/dL).
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).
Agree to use adequate birth control, if of childbearing potential.

Exclusion Criteria:

Has radiographic evidence of pancreatic cancer recurrence.
Has any documented history of autoimmune diseases including systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis,or vasculitis.
Has any uncontrolled medical problems.
Has had systemic steroid therapy within 28 days before vaccine administration.
Has an anticipated need for systemic steroid therapy within 28 days after vaccine administration.
Has any evidence of active infections.
Is pregnant.
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.
Has a history of noncompliance during previous vaccination cycles with study treatment and/or monitoring which is concerning for continued noncompliance.