Vaccine Therapy in Treating Patients With Liver or Lung Metastases From Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
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 Granulocyte-macrophage colony-stimulating factor (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 with liver or lung metastases from colorectal cancer removed by surgery.

Detailed Description
-----------------
OBJECTIVES: Primary Compare 2-year disease-free survival of patients with completely resected hepatic or pulmonary metastases secondary to colorectal cancer treated with adjuvant vaccine therapy comprising vaccinia-Carcinoembryonic antigen (CEA)-mucin 1 (MUC-1)- Triad of costimulatory molecules 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 enzyme-linked immunosorbent spot (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 subcutaneously (SC) and intradermally (ID) on days 28, 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.

Official Title
-----------------
A Phase II Study of Active Immunotherapy With PANVAC or Autologous, Cultured Dendritic Cells Infected With PANVAC After Complete Resection of Hepatic or Pulmonary Metastases of Colorectal Carcinoma

Conditions
-----------------
Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
-----------------
* Biological: falimarev
* Biological: inalimarev
* Biological: sargramostim
* Biological: therapeutic autologous dendritic cells


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed hepatic or pulmonary metastases secondary to adenocarcinoma of the colon and rectum Must have undergone complete resection of hepatic or pulmonary metastases with curative intent No evidence of gross residual disease after surgery One or more resected and ablated lesions allowed provided all gross residual tumor was destroyed by ablation Repeated resections of hepatic metastatic disease or resections of extrahepatic metastases prior to resection of the hepatic metastases allowed provided the most recent hepatic metastatic resection included total disease resection and/or ablation Must have received at least 2 months of perioperative systemic chemotherapy (including preoperative and/or postoperative chemotherapy) that was completed at least 1 month ago PATIENT CHARACTERISTICS: Age At least 18 Performance status Karnofsky 70-100% Life expectancy At least 6 months Hematopoietic Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 8.5 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 human immunodeficiency virus (HIV) infection by enzyme-linked immunosorbent assay (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 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 Other No other concurrent immunosuppressants (e.g., azathioprine or cyclosporine)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PANVAC-V + PANVAC-F + DC<br>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 28, 56, and 84. | Biological: falimarev<br>* Given subcutaneously and intradermally<br>Biological: inalimarev<br>* Given subcutaneously and intradermally<br>Biological: therapeutic autologous dendritic cells<br>* Given subcutaneously and intradermally<br>|
| Experimental: PANVAC-V + PANVAC-F + GM-CSF<br>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. | Biological: falimarev<br>* Given subcutaneously and intradermally<br>Biological: inalimarev<br>* Given subcutaneously and intradermally<br>Biological: sargramostim<br>* Given subcutaneously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free Survival at 2 Years | Recurrence-free survival for randomized patients receiving dendritic cells (DC) loaded with PANVAC or PANVAC plus Granulocyte-macrophage colony-stimulating factor (GM-CSF) measured from the date of metastasectomy, with relapse defined as documented disease recurrence at any site. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive Immune Response as Measured by (Enzyme-linked Immunosorbent Spot) ELISpot Assay | CEA-Specific Immune Responders by enzyme-linked immunosorbent spot (ELISpot). The ELISPOT assay is considered positive for a subject if the mean number of spots with CEA exceeds the number of spots with control by a magnitude of 10 and the difference between CEA and control is statistically significant at a level of p=0.05 by the t-test. | 13 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the rectum, recurrent rectal cancer, stage IV rectal cancer, lung metastases, liver metastases, adenocarcinoma of the colon, recurrent colon cancer, stage IV colon cancer