vaccine therapy with or without interleukin-2 in treating patients with locally advanced or metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: 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.

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.

Eligibility criteria:
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

Keywords: stage iii colon cancer stage iv colon cancer stage iii rectal cancer stage iv rectal cancer recurrent colon cancer recurrent rectal cancer