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

NCT ID: NCT01191684

Last Updated: 2017-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2013-08-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (vaccine therapy)

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

Group Type: EXPERIMENTAL

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

enzyme-linked immunosorbent assay

Intervention Type: OTHER

Correlative studies

flow cytometry

Intervention Type: OTHER

Correlative studies

immunoenzyme technique

Intervention Type: OTHER

Correlative studies

modified vaccinia virus ankara vaccine expressing p53

Intervention Type: BIOLOGICAL

Given SC

Interventions

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

enzyme-linked immunosorbent assay

Correlative studies

Intervention Type: OTHER

flow cytometry

Correlative studies

Intervention Type: OTHER

immunoenzyme technique

Correlative studies

Intervention Type: OTHER

modified vaccinia virus ankara vaccine expressing p53

Given SC

Intervention Type: BIOLOGICAL

Other Intervention Names

ELISA; immunoenzyme techniques; MVA-p53 vaccine; MVAp53 vaccine

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vincent Chung, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24987057 (View on PubMed)

Other Identifiers

NCI-2010-01859

Identifier Type: -

Identifier Source: secondary_id

10105

Identifier Type: -

Identifier Source: org_study_id