A Trial of Boost Vaccinations of Pancreatic Tumor Cell Vaccine

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Biological: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.

Detailed Description

Primary Objective:

1. 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:

1. 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.
2. To estimate disease-free and overall survival of surgically resected pancreatic adenocarcinoma patients treated with vaccine boosts with or without low dose cyclophosphamide.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lei Zheng, M.D., Ph.D; Phone Number: 410-955-8893; Email: lzheng6@jhmi.edu
• Study Contact Backup: Name: Carol A Judkins, RN; Phone Number: 410-614-5241; Email: judkica@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: The Skip Viragh Foundation
• Investigators: Principal Investigator: Lei Zheng, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2010
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: March 1, 2010
• First Submitted That Met QC Criteria: March 16, 2010
• First Posted (Estimated): March 17, 2010

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Adenocarcinoma; Cyclophosphamide; GM-CSF; Neo-Adjuvant; Randomize; Pancreatic tumor vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: J09100; NA_00031401 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data entry and analysis is still ongoing.