Vaccine Therapy and Chemotherapy With or Without Tetanus Toxoid Compared With Chemotherapy Alone in Treating Patients With 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 to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Tetanus toxoid may make tumor cells more sensitive to chemotherapy and vaccine therapy. PURPOSE: Randomized phase II trial to study the effectiveness of chemotherapy and vaccine therapy with or without tetanus toxoid compared with chemotherapy alone in treating patients who have metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Determine the safety of ALVAC-CEA-B7.1 vaccine and chemotherapy, with or without tetanus toxoid, vs chemotherapy alone in patients with metastatic colorectal adenocarcinoma. Determine whether tetanus toxoid enhances the immune response in patients treated with the vaccine and chemotherapy. OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive a priming dose of tetanus toxoid. Beginning 2 weeks later, patients receive tetanus toxoid and ALVAC-CEA-B7.1 vaccine subcutaneously (SC) once weekly for 3 weeks. Two weeks after the third vaccine administration, patients receive tetanus toxoid and ALVAC-CEA-B7.1 vaccine SC on day 1 and irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive ALVAC-CEA-B7.1 vaccine and chemotherapy as in arm I. Arm III: Patients receive chemotherapy as in arm I. After completion of chemotherapy, patients with partial or complete response may receive ALVAC-CEA-B7.1 vaccine SC once weekly on weeks 1-3 and 6. PROJECTED ACCRUAL: A total of 90 patients (30 per treatment arm) will be accrued for this study.

Official Title
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Pilot Phase II Study of Safety and Immunogenicity of an ALVAC-CEA/B7.1 Vaccine Administered With Chemotherapy, Alone or in Combination With Tetanus Toxoid, as Compared to Chemotherapy Alone, in Patients With Metastatic Colorectal Adenocarcinoma

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: ALVAC-CEA-B7.1 vaccine
* Biological: tetanus toxoid
* Drug: FOLFIRI regimen
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed metastatic colorectal adenocarcinoma No clinically active CNS metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: More than 6 months Hematopoietic: Lymphocyte count at least 1,000/mm^3 Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) AST/ALT less than 3 times ULN (5 times ULN if liver metastases present) Alkaline phosphatase less than 3 times ULN (5 times ULN if liver metastases present) No hepatocellular dysfunction No cirrhosis Renal: Creatinine less than 2.5 mg/dL Cardiovascular: No uncontrolled coronary artery disease No symptomatic congestive heart failure Pulmonary: No uncontrolled chronic obstructive lung disease Gastrointestinal: No unsolved bowel obstruction or subobstruction No uncontrolled Crohn's disease No ulcerative colitis No concurrent chronic diarrhea Immunologic: HIV negative No immunocompromised patients No diagnosis of altered immune function, including: Lupus erythematosus Sjogren's syndrome Scleroderma Myasthenia gravis Goodpasture's disease Addison's disease Hashimoto's thyroiditis Active Graves' disease No known allergy to egg products or neomycin No prior adverse reaction to tetanus toxoid-containing vaccines Other: No significant comorbid medical function No uncontrolled infection No unstable diabetes mellitus No uncontrolled thyroid function abnormalities No other malignancy within the past 5 years except basal cell carcinoma or adequately treated carcinoma in situ of the cervix No other medical illness or mental status that would preclude study participation No prior severe toxicity to adjuvant chemotherapy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy: No prior CEA-directed immunotherapy No other concurrent immunotherapy Chemotherapy: At least 6 months since prior adjuvant chemotherapy No prior chemotherapy for metastatic disease No other concurrent chemotherapy Endocrine therapy: No concurrent daily use of systemic steroids No concurrent nonsubstitutional hormonal therapy Radiotherapy: No prior radiotherapy to more than 50% of all nodal groups No concurrent radiotherapy except for palliative purposes involving less than 20% of bone marrow reserve Surgery: No prior major organ allograft Recovered from prior surgery Other: At least 28 days since prior investigational products No other concurrent investigational products

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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: ALVAC-CEA-B7.1 vaccine|nan|
|Biological: tetanus toxoid|nan|
|Drug: FOLFIRI regimen|nan|
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Drug: leucovorin calcium|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum