Vaccine Therapy in Treating Patients With Colorectal, Stomach, or Pancreatic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01191684
First received: August 27, 2010
Last updated: August 21, 2013
Last verified: August 2013
  Purpose

RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with colorectal, stomach, or pancreatic cancer.


Condition Intervention Phase
Recurrent Colon Cancer
Recurrent Gastric Cancer
Recurrent Pancreatic Cancer
Recurrent Rectal Cancer
Stage III Colon Cancer
Stage III Gastric Cancer
Stage III Pancreatic Cancer
Stage III Rectal Cancer
Stage IV Colon Cancer
Stage IV Gastric Cancer
Stage IV Pancreatic Cancer
Stage IV Rectal Cancer
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Other: flow cytometry
Other: immunoenzyme technique
Biological: modified vaccinia virus ankara vaccine expressing p53
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of an MVA Vaccine Targeting P53 in Cancer

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Safety and tolerance of modified vaccinia virus ankara vaccine expressing p53 assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4 toxicity scale [ Time Frame: Assessed up to 12 months ] [ Designated as safety issue: Yes ]
    Safety data for each administered dose will be summarized using descriptive numbers and 95% confidence intervals from the exact binomial distributions


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: Assesse up to 12 months ] [ Designated as safety issue: No ]
    Assessed using enzyme-linked immunosorbent assay (ELISA) for humoral response, lymphoproliferation for cluster of differentiation (CD)4+ T cell response, and intracytoplasmic cytokine assays, and interferon (IFN)-gamma and interleukin (IL)-4 by enzyme-linked immunosorbent spot (ELISPOT) for the assessment of cellular immune response. For each assay, the pre-vaccine values will be compared to the highest post-vaccine values. Immunogenicity changes and the maximum change will be quantified by mean, standard deviation, median, and range and tested by paired t-test at the 0.05 significance level.


Enrollment: 12
Study Start Date: October 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vaccine therapy)
Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.
Other: laboratory biomarker analysis
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: flow cytometry
Correlative studies
Other: immunoenzyme technique
Correlative studies
Other Name: immunoenzyme techniques
Biological: modified vaccinia virus ankara vaccine expressing p53
Given SC
Other Names:
  • MVA-p53 vaccine
  • MVAp53 vaccine

Detailed Description:

PRIMARY OBJECTIVES:I. To establish whether 2 vaccine dose levels of modified vaccinia virus ankara vaccine expressing p53 (MVAp53) vaccines are safe and well tolerated in patients with p53 over-expressing solid tumor malignancy.

SECONDARY OBJECTIVES:I. To provide preliminary evidence of enhanced cellular and humoral immunity to p53.

OUTLINE:This is a phase I, dose-escalation trial of modified vaccinia virus ankara vaccine expressing p53 (MVAp53).Patients receive MVAp53 subcutaneously (SC) on days 0, 21, and 42 in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up annually for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with unresectable and chemotherapy resistant primary or recurrent carcinoma of colorectal, gastric or pancreatic origin
  • There must be pathologic evidence for malignancy with a soft tissue component of tumor evident on CT scan imaging or physical examination
  • Patient must be able to give informed consent
  • There must be an anticipated survival of at least 3 months
  • Performance status of 80-100 (Karnofsky performance status)
  • WBC count >= 3,000uL
  • Platelet count >= 100,000uL
  • Prothrombin time and partial thromboplastin time of <= 1.5 times the upper limit of normal
  • Women of childbearing potential must have a negative pregnancy test; women and men of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant during or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • Patients with asymptomatic small volume bone disease not likely to require radiation therapy during the period of the vaccine trial will be eligible
  • Hemoglobin level > 9g/dL
  • There must be evidence of p53 over expression by immunohistochemistry with > 10% of cells within the tumor strongly positive
  • Patients with colorectal cancer will need to have failed to respond to 5-FU based therapy with oxaliplatin, irinotecan as well as epidermal growth factor receptor (EGFR) directed therapies (if appropriate); patients with gastric cancer will need to have progressed on standard first line chemotherapy or chemoradiotherapy and Herceptin based therapy (if appropriate); patients with pancreatic cancer who have failed to respond to at least 1 chemotherapy regimen

Exclusion Criteria:

  • Diagnosis which has been associated with immunodeficiency, including HIV
  • Prior radiation to more than 50% of all nodal groups
  • Concurrent use of corticosteroids
  • History of another malignancy, other than nonmelanoma skin cancer in the past 2 years
  • Recent major surgery
  • Serious intercurrent illness
  • Temperature >= 101F within 3 days prior to the initial injection
  • Pregnancy or lactation
  • Clinically evident brain metastasis
  • Autoimmune disease
  • HIV seropositivity or refusal to hear the results of the HIV test
  • Receipt of organ grafts
  • History of severe environmental allergies
  • History of severe neurological, cardiovascular, renal, hepatic, endocrine, respiratory, or bone marrow dysfunction requiring frequent re-evaluation, and management by a physician
  • Patients with a history of congestive heart failure or coronary artery disease which has not been resolved by bypass or stent
  • History of myopericarditis
  • Known family history of Li-Fraumeni syndrome
  • Allergy to egg proteins
  • Chemotherapy or radiation within the 4 weeks preceding enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191684

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Vincent Chung, MD City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01191684     History of Changes
Other Study ID Numbers: 10105, NCI-2010-01859
Study First Received: August 27, 2010
Last Updated: August 21, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Stomach Neoplasms
Pancreatic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Stomach Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 28, 2014