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

Primary Purpose

Recurrent Colon Cancer, Recurrent Gastric Cancer, Recurrent Pancreatic Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

laboratory biomarker analysis

enzyme-linked immunosorbent assay

flow cytometry

immunoenzyme technique

modified vaccinia virus ankara vaccine expressing p53

About this trial

This is an interventional treatment trial for Recurrent Colon Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

City of Hope Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (vaccine therapy)

Arm Description

Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.

Outcomes

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

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

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.

Full Information

NCT ID

NCT01191684

First Posted

August 27, 2010

Last Updated

July 28, 2017

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01191684

Brief Title

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

Official Title

A Phase I Study of an MVA Vaccine Targeting P53 in Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

August 2013 (Actual)

Study Completion Date

August 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (vaccine therapy)

Arm Type

Experimental

Arm Description

Patients receive MVAp53 subcutaneously on days 0, 21, and 42 in the absence of unacceptable toxicity.

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

enzyme-linked immunosorbent assay

Other Intervention Name(s)

ELISA

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

flow cytometry

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

immunoenzyme technique

Other Intervention Name(s)

immunoenzyme techniques

Intervention Description

Correlative studies

Intervention Type

Biological

Intervention Name(s)

modified vaccinia virus ankara vaccine expressing p53

Other Intervention Name(s)

MVA-p53 vaccine, MVAp53 vaccine

Intervention Description

Given SC

Primary Outcome Measure Information:

Title

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

Description

Safety data for each administered dose will be summarized using descriptive numbers and 95% confidence intervals from the exact binomial distributions

Time Frame

Assessed up to 12 months

Secondary Outcome Measure Information:

Title

Immunogenicity

Description

Time Frame

Assesse up to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vincent Chung, MD

Organizational Affiliation

City of Hope Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

City of Hope Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24987057

Citation

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. Erratum In: Clin Cancer Res. 2017 Jan 1;23 (1):322.

Results Reference

result

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

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