Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response that will kill cancer cells. Combining vaccine therapy with interleukin-2 may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy with or without interleukin-2 in treating patients who have locally advanced or metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Determine the frequency of immunologic response in patients with locally advanced or metastatic colorectal cancer treated with ras peptide-pulsed dendritic cell vaccine with or without interleukin-2. Determine the tumor response and survival time in patients with metastatic colorectal cancer treated with vaccine plus interleukin-2. Determine the time to progression in patients with locally advanced colorectal cancer treated with adjuvant vaccine. OUTLINE: Patients are assigned to 1 of 2 treatment groups according to extent of disease. Patients with prior locally advanced disease are assigned to treatment group A, while those with metastatic disease are assigned to treatment group B. Group A: Patients are vaccinated against influenza on day -6. Patients undergo collection of peripheral blood mononuclear cells (PBMC) on day -4. The PBMC are cultured with sargramostim (GM-CSF) and interleukin-4 for 5 days and CD40 ligand for 24 hours and then pulsed for 2 hours with the appropriate peptide to form a vaccine. Patients receive ras peptide-pulsed dendritic cell vaccine IV over 5 minutes on days 1, 15, 29, 43, and 57. Group B: Patients undergo collection of PBMC and receive vaccination as in group A. Patients also receive interleukin-2 subcutaneously on days 2-6 and 9-13. Treatment in both groups repeats every 2 weeks for up to 5 vaccinations in the absence of disease progression or unacceptable toxicity. Patients are followed on days 75, 90, 120, and 365. PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study within 3 years.

Official Title
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A Phase I/II Trial of Vaccination With Mutant Ras Peptide-Pulsed Dendritic Cells in the Treatment of HLA A2.1 Positive Patients With Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: aldesleukin
* Biological: ras peptide cancer vaccine
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed locally advanced or metastatic colorectal cancer Metastatic disease must be radiologically proven HLA-A2-1 positive Locally advanced disease must have had prior resection or incomplete resection with poor prognosis Locally advanced disease includes: Stage III or IV colon cancer (T4 or any T, N2-3, M0) Stage III or IV rectal cancer (T4 or T3, N1-3) Resectable or unresectable T4 disease after radiotherapy, chemotherapy, and/or surgery Absence of measurable disease but more than a 50% chance of recurrence Completely resected or locally advanced disease may have had conventional therapy completed within 1-12 months (surgery alone, with or without adjuvant chemotherapy and/or radiotherapy) prior to study entry Metastatic disease patients must have bidimensionally measurable disease Bone lesions with well-demarcated borders allowed Lesions seen only on bone scan, pleural effusions, ascites, and changes in carcinoembryonic antigen are not considered measurable disease PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Lymphocyte count at least 470/mm^3 Granulocyte count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 2.0 mg/dL* SGOT no greater than 4 times upper limit of normal (ULN) (2.5 times ULN for adjuvant patients)* Albumin at least 3 g/dL No active viral hepatitis No evidence of chronic infection due to hepatitis C Hepatitis B surface antigen negative NOTE: *Unless due to metastatic disease Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No history of cardiac failure, significant arrhythmias, or coronary artery disease (metastatic disease patients only) Other: Not pregnant or nursing Fertile patients must use effective contraception HIV negative No prior malignancy with a 50% chance of recurrence within 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix No medical or psychiatric condition that would preclude compliance No serious medical condition that would preclude apheresis No serious infection No uncontrolled thyroid disease (metastatic disease patients only) Patients with an allergy to eggs are allowed but are not vaccinated against influenza during study PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunologic therapy directed at the cellular immune system Chemotherapy: See Disease Characteristics Prior chemotherapy for metastatic disease allowed At least 4 weeks since prior chemotherapy No concurrent chemotherapy or anticipated need for chemotherapy for 2 months after vaccinations Endocrine therapy: At least 4 weeks since prior supraphysiologic steroid therapy Radiotherapy: See Disease Characteristics Prior radiotherapy for metastatic disease allowed No concurrent radiotherapy Surgery: See Disease Characteristics Prior surgery for metastatic disease allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Biological: ras peptide cancer vaccine|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate every 3 months for up to a year after completion of study treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer