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.

Condition	Treatment or Intervention	Phase
stage IV colon cancer Stage IV rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum	Drug: ALVAC-CEA-B7.1 vaccine  Drug: fluorouracil  Drug: irinotecan  Drug: leucovorin calcium  Drug: tetanus toxoid  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: non-specific immune-modulator therapy  Procedure: recombinant viral vaccine  Procedure: vaccine therapy	Phase II

Further Study Details: 

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.

• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35243,  United States
California
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States
District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
Oregon
      Earle A. Chiles Research Institute at Providence Portland Medical Center, Portland,  Oregon,  97213-2967,  United States
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      Scranton Hematology-Oncology, Scranton,  Pennsylvania,  18510,  United States
Canada, Ontario
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
Canada, Quebec
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada

Study chairs or principal investigators

Howard L. Kaufman, MD,  Study Chair,  Columbia Presbyterian Medical Center   

Study ID Numbers:  CDR0000069082; CPMC-14534; CPMC-BB-IND-9911; FCCC-01015; APL-COL13; NCI-G01-2033
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  December 7, 2001
ClinicalTrials.gov Identifier:  NCT00027833
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08