Vaccine Therapy and Radiation to Liver Metastasis in Patients With CEA-Positive Solid Tumors

Phase 1

Completed

• Conditions: Liver Neoplasms

• Registration Number: NCT00081848
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This study will evaluate the safety and effects of vaccine treatment plus radiation to the liver in patients with solid tumors that have spread to the liver. The vaccine treatment consists of three parts: 1) a "priming vaccine" called rV-CEA(6D)-TRICOM, made from vaccinia virus; 2) a "boosting vaccine" called rF-CEA(6D)-TRICOM), made from fowlpox virus; and 3) a fowlpox virus injected with DNA for GM-CSF, a chemical that boosts the immune system, called rF-GM-CSF. Human DNA is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce carcinoembryonic antigen (CEA) - a protein that is normally produced by the patient's tumor cells. The study also uses radiation, because laboratory and animal studies show that low doses of radiation to tumors that produce CEA make the tumor more sensitive to the effects of the vaccines.

Patients 18 years of age and older who have a solid tumor that has spread to the liver may be eligible for this study. Candidates must have had at least one course of chemotherapy for metastatic disease and their tumor must produce CEA. Candidates are screened with a medical history and physical examination; blood and urine tests, test of pathology slides from surgery to determine the presence of the CEA marker, imaging studies to assess the extent of tumor, and an electrocardiogram (and cardiologic evaluation, if clinically indicated).

Participants receive the priming vaccination on study day 1. After 3 weeks and then again every 2 weeks for 2 months (study days 21, 35, 49 and 63), they receive a boosting vaccine. All vaccines are injected under the skin. With every vaccination they also receive an injection of rF-GM-CSF to increase the number of immune cells at the vaccination site. The day after each of the first four boosting vaccinations, patients undergo 4 consecutive days of radiation to the tumor in the liver (study days 22-25, 36-39, 50-53 and 64-67). Patients may continue treatment with monthly booster vaccinations (without further radiation therapy) as long as their cancer does not get worse and they do not develop serious treatment side effects.

Patients are monitored for safety and treatment response with the following tests and procedures:

* Blood and urine tests and clinic visits every 2 to 4 weeks to monitor liver, kidney, and other organ function.

* Imaging studies to assess the tumor around study day 91 and every 2 months after that while on the study.

* Apheresis (a procedure for collecting immune cells called lymphocytes) - Apheresis is done before the first vaccination on study day 1 and again around study day 91. For this procedure, blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components by spinning, and the lymphocytes are extracted. The rest of the blood is returned to the patient through the same needle. The collected lymphocytes are studied to measure the immune response to treatment.

* Liver biopsy (optional) - This test is done once before starting radiation treatment and again around 3 to 7 days after completing the first dose of radiation. The biopsy provides information on the type of cancer, the level of CEA produced by the tumor, and the immune status of the tumor. For this procedure, the skin over the liver is numbed with an anesthetic, a needle is placed in the liver tumor, and a small sample of tumor is withdrawn through the needle.

After treatment is completed, patients are monitored for up to 15 years, including yearly medical histories and physical examinations for 5 years following their last vaccination. Information beyond 5 years is collected once a year by telephone

Detailed Description

Background:

* A phase I clinical trial with this same vaccine alone was associated with stable disease (at least 4 months) in 40% of patients and 1 pathologic complete response.

* Radiation therapy upregulates Fas on tumor cells allowing for easier killing by antigen specific activated T cells. Dominant negative fas transfected tumor cells demonstrated the anti-tumor effects were fas mediated.

* Radiation has been shown to up-regulate ICAM, tumor associated antigens and MHC class I on human tumor cell lines in vitro.

* TRICOM vaccines act synergistically with radiation in tumor treatment models.

* Radiation therapy at the doses we propose appears to have a favorable safety profile.

* Clinical trials using PSA vaccine shows that local radiation of tumor does not inhibit vaccine efficacy.

Objectives:

* 1: Safety of the combination of a CEA based vaccine and radiation

* 2: clinical response

* 2: Immunohistochemistry - (FAS, MHC, p53 and CEA on tumor before and after radiation therapy)

* 2: Immunological response (ELISPOT assay).

Eligibility:

* Solid Tumors expressing CEA positive cancer with radiographically visible metastatic liver lesions.

* Completed at least one chemotherapy regimen for metastatic disease.

* Life expectancy greater than or equal to 6 months

* Adequate organ function

* ECOG 0-1

* No autoimmunity

* No serum positivity for HIV, Hepatitis B or C viruses

Design:

* Single cohort pilot study of vaccine and radiation therapy to liver lesions in 10 evaluable patients. All vaccines and radiation are given at the NIH Clinical Center.

* Vaccine:

rV-CEA(6D)/TRICOM, (1.2 x 10(8)) PFU subcutaneously (s.c.) day 1

rF-CEA(6D)/TRICOM, (4 x 10(8)) PFU s.c., days 21, 35, 49, and 63

All vaccinations will be given with rF-GM-CSF, 1 x 10(7) pfu s.c.

-Radiation: 2 Gy/d for 4 days after each dose of rF-CEA(6D)/TRICOM on days 22-25, 36-39, 50-53, and 64-67 (total planned radiation dose per patient is 32 Gy).

Study Timeline

• Study Start: 2004-04-20
• Study First Submitted QC: 2004-04-21
• Study First Submitted: 2004-04-22
• Study First Posted: 2004-04-22
• Primary Completion: 2007-08-23
• Study Completion: 2007-08-23
• Status Verified: 2012-01-25
• Last Update Submitted: 2017-06-30
• Last Update Posted: 2017-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States