RATIONALE: Vaccines made from a gene-modified virus and a person’s white blood cells may make the body build an effective immune response to kill tumor cells. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying giving vaccine therapy together with dendritic cells to see how well it works compared to giving vaccine therapy together with GM-CSF in treating patients who have had liver metastases from colorectal cancer removed by surgery.

Condition	Treatment or Intervention	Phase
Colon Cancer liver metastases Rectal Cancer	Drug: autologous dendritic cells  Drug: fowlpox-CEA-MUC-1-TRICOM vaccine  Drug: sargramostim  Drug: vaccinia-CEA-MUC-1-TRICOM vaccine  Procedure: adjuvant therapy  Procedure: biological response modifier therapy  Procedure: non-specific immune-modulator therapy  Procedure: non-tumor cell derivative vaccine  Procedure: recombinant viral vaccine  Procedure: vaccine therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare 2-year disease-free survival of patients with completely resected hepatic metastases secondary to colorectal cancer treated with adjuvant vaccine therapy comprising vaccinia-CEA-MUC-1-TRICOM vaccine (PANVAC-V) and fowlpox-CEA-MUC-1-TRICOM vaccine (PANVAC-F) administered with autologous dendritic cells or with sargramostim (GM-CSF).

Secondary

• Compare the rate and magnitude of immune response, as determined by ELISpot, in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Patients then receive autologous DC loaded with vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) vaccine subcutaneously (SC) and intradermally (ID) on day 1 and autologous DC loaded with fowlpox-CEA-MUC-1-TRICOM (PANVAC-F) vaccine SC and ID on days 2, 8, 56, and 84.
• Arm II: Patients receive PANVAC-V SC on day 1 and PANVAC-F SC on days 28, 56, and 84. Patients also receive sargramostim (GM-CSF) SC into the same injection site once daily on days 0-3, 28-31, 56-59, and 84-87. After completion of study treatment, patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 72 patients (36 per treatment arm) will be accrued for this study within 2 years.

Ages Eligible for Study:  5 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed hepatic metastases secondary to adenocarcinoma of the colon and rectum
• Must have undergone complete resection of hepatic metastases with curative intent
• No evidence of gross residual disease
• One or more resected and ablated lesions allowed provided all gross residual tumor was destroyed by ablation
• Must have received up to 6 months of adjuvant chemotherapy that was completed within the past 1-3 months

PATIENT CHARACTERISTICS: Age

• Over 5

Performance status

• Karnofsky 80-100%

Life expectancy

• More than 6 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 9 g/dL (transfusion or epoetin alfa allowed)

Hepatic

• Bilirubin < 2.0 mg/dL
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative
• No other serious chronic or acute hepatic disease

Renal

• Creatinine < 1.5 mg/dL OR
• Creatinine clearance > 60 mL/min

Cardiovascular

• No New York Heart Association class III or IV cardiac disease
• No other serious chronic or acute cardiac disease

Pulmonary

• No asthma
• No chronic obstructive pulmonary disease
• No other serious chronic or acute pulmonary disease

Immunologic

• No history of autoimmune disease, including, but not limited to, any of the following:
• Inflammatory bowel disease
• Systemic lupus erythematosus
• Ankylosing spondylitis
• Scleroderma
• Multiple sclerosis
• No HIV infection by ELISA and western blot
• Not immunocompromised (by disease or therapy)
• No allergy to eggs or any component of the study vaccine
• No history of allergy or untoward reaction to prior vaccinia (smallpox) vaccination
• No allergy or untoward reaction to sargramostim (GM-CSF)
• No active acute or chronic infection, including urinary tract infection within the past 72 hours
• No inflammatory bowel conditions, including, but not limited to, the following:
• Active infectious enteritis
• Eosinophilic enteritis
• No acute, chronic, or exfoliative skin disorders, including any of the following:
• Extensive psoriasis
• Burns
• Impetigo
• Disseminated zoster
• Varicella zoster
• Severe acne
• Other open rashes or wounds

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Weight > 50 kg
• Able to avoid close contact or household contact for 3 weeks after each vaccination with the following individuals:
• Children under 5 years of age
• Pregnant or nursing women
• Individuals with prior or concurrent extensive eczema, other eczematoid skin disorders, or other acute or chronic skin conditions
• Immunosuppressed or immunodeficient individuals
• No medical or psychological condition that would preclude study compliance
• No extensive eczema
• No other serious chronic or acute illness that would preclude study participation
• No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled superficial bladder cancer, or previously treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No other concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy

• More than 6 weeks since prior and no concurrent steroid therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• No prior splenectomy

Other

• No other concurrent immunosuppressants (e.g., azathioprine or cyclosporine)

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting

Study chairs or principal investigators

Michael A. Morse, MD,  Study Chair,  Duke Comprehensive Cancer Center   

Study ID Numbers:  CDR0000410791; DUMC-5883-04-6RO; NCT00103142
Record last reviewed:  February 2005
Last Updated:  March 10, 2005
Record first received:  February 7, 2005
ClinicalTrials.gov Identifier:  NCT00103142
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08