Vaccine Therapy In Treating Patients With Colorectal, Stomach, Or Pancreatic Cancer

Study Overview

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

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.

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.

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

10105
NCI-2010-01859

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-08-27	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2017-07-28
First Submitted that Met QC Criteria 2010-08-30	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2017-08-01
First Posted (ACTUAL) 2010-08-31	Results First Posted N/A	Last Verified 2017-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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: flow cytometry Correlative studies OTHER: immunoenzyme technique Correlative studies BIOLOGICAL: modified vaccinia virus ankara vaccine expressing p53 Given SC

Participant Group/Arm

Intervention/Treatment

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: flow cytometry

Correlative studies

OTHER: immunoenzyme technique

Correlative studies

BIOLOGICAL: modified vaccinia virus ankara vaccine expressing p53

Given SC

Primary Outcome Measures	Measure Description	Time Frame
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	Safety data for each administered dose will be summarized using descriptive numbers and 95% confidence intervals from the exact binomial distributions	Assessed up to 12 months

Secondary Outcome Measures	Measure Description	Time Frame
Immunogenicity	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.	Assesse up to 12 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Vincent Chung, MD, City of Hope Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Hardwick NR, Carroll M, Kaltcheva T, Qian D, Lim D, Leong L, Chu P, Kim J, Chao J, Fakih M, Yen Y, Espenschied J, Ellenhorn JD, Diamond DJ, Chung V. p53MVA therapy in patients with refractory gastrointestinal malignancies elevates p53-specific CD8+ T-cell responses. Clin Cancer Res. 2014 Sep 1;20(17):4459-70. doi: 10.1158/1078-0432.CCR-13-3361. Epub 2014 Jul 1.

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Clinical Trial Record