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

Completed · Phase 1

Conditions studied: Liver Neoplasms

In brief

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

Key facts

Study ID: NCT00081848
Run by: National Cancer Institute (NCI)
People needed: 12
Starts: 2004-04-20
Expected to finish: 2007-08-23
Last updated by the study team: 2017-07-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients should have no evidence of being immunocompromised as listed below.
Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects
Autoimmune diseases such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome active Grave's disease. Altered immune function in prospective participants will be assessed through a thorough history and physical examination. Any clinical suspicion of autoimmune dysfunction will be worked up before enrollment on to the study. This requirement is due to the potential risks of exacerbating autoimmunity
Hepatitis B or C positivity
Prior radiation to greater than 50% of all nodal groups
Prior whole liver radiation
Concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Steroid eye drops are contraindicated for at least 2 weeks prior vaccinia vaccination and at least 4 weeks post vaccinia vaccination.
Prior splenectomy
History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen.
Pregnant or breast-feeding women.
Recombinant vaccinia vaccination should not be administered if any of the following apply to either recipients, or for at least three weeks after vaccination (i.e., until the scab has separated from the skin and the underlying skin has healed), their close household contacts (close household contacts are those who share housing or have close physical contact): persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 5 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection.
Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis.
Known brain metastasis, history of seizures, encephalitis, or multiple sclerosis.
Concurrent chemotherapy.
Serious hypersensitivity reaction to egg products.
Clinically significant cardiomyopathy requiring treatment.
Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with ordinary physical activity (New York Heart Association class 2 or greater) are not eligible.
Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical activity are not eligible.
Patients who have objective evidence of congestive heart failure by physical exam or imaging are not eligible.
Chronic liver disease including end stage cirrhosis, or chronic active hepatitis as indicated by surface antigen or core antibody.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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