UAB 0135

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

PRINCIPAL INVESTIGATOR: Robert M. Conry, M.D.

SPONSOR: Aventis Pasteur Limited

OBJECTIVES

1. To evaluate the safety of ALVAC-CEA/B7.1 administered concurrently with chemotherapy (Groups 1 and 2)
2. To determine whether Tetanus Toxoid (non-absorbed) will enhance the immune response induced by ALVAC-CEA/B7.1 administerd concurrently with chemotherapy (Group 2 versus Group 1).

PATIENT SELECTION CRITERIA

Inclusion Criteria

Questions about eligibility criteria must be addressed prior to treatment. The following criteria must be met:

1. Patients must have been diagnosed with histologically confirmed metastatic colorectal adenocarcinoma.
2. Patients must be HLA-A02 positive.
3. Patients must be ambulatory, with an ECOG performance status of 0 to 1 and life expectancy > 6 months.
4. Patients must be 18 years or older.
5. Patients or a legally acceptable representative must sign a written, informed consent that has been approved by the Institutional Review Board.
6. Patients must be able to cooperate with the requirements of the study (appear to understand the information regarding the study and be accessible for the duration of the study.)
7. Female patienst of childbearing potential must be neither pregnant nor breastfeeding and must have a negative serum pregnancy test within 14 days prior to entry.
8. Patients must agree to use effective contraception (birth control pills, condoms, approved implant, or IUD) during the treatment period and for at least three months after the last injection.
9. Patients must be fully recovered from surgery (if applicable), as judged by the investigator.
10. Patient baseline laboratory values must be within the following ranges (unless abnormalities are due to malignant disease):
    • Hemoglobin - > 10 g/dL (> 100g/L)
    • Granulocytes - > 1500/mm3 (> 1.5 x 109/L)
    • Lymphocytes - > 1000/mm3 (> 1.0 x 109/L)
    • Platelets - > 100,000/m3 (> 100 x 109/L)
    • Serum Creatinine - < 2.5 mg/dL
    • Serum Total Bilirubin - < 1.5 x the normal upper limit
    • AST, ALT, and ALP - < 3 x the normal upper limit, or < 5 x the normal upper limit if due to liver metastases.

Exclusion Criteria

Patients who meet the following exclusion criteria will not be eligible for admission to the study:

1. Prior chemotherapy:
   • Patients must not have received chemotherapy for their metastatic disease
   • Prior adjuvant therapy is allowed if it was completed 6 months prior to enrollment.
2. Medical illness or mental status that would preclude cooperation with the study
   requirements or the interpretation of safety data.
3. Evidence of being immunocompromised, as defined by:
   • HIV positive status, determined by patient history
   • Diagnosis of altered immue function, including uncontrolled autoimmune disease such as lupus erythematous, Sjogren syndrome, scleroderma, myasthemia gravis, Goodpasture syndrome, Addison's disease, Hashimoto's thyroiditis, or active Graves' disease.
   • Prior radiation to >50% of all nodal groups
   • Concurrent daily use of systemic steroids.
4. Singnificant co-morbid medical problems, including:
   • Unsolved bowel obstruction or subobstruction, uncontrolled Crohn's disease, or ulcerative colitis.
   • current chronic diarrhea
   • Uncontrolled coronary artery disease
   • Uncontrolled infection
   • Uncontrolled chronic obstructive lung disease
   • Unstable diabetes mellitus
   • Hepatocellular dysfunction/cirrhosis
   • Uncontrolled thyroid function abnormalities
   • Presence within the last five years of a second primary tumor, except basal cell carcinoma or adequately treated in situ carcinoma of the cervix.
5. Clinically active central nervous system metastses (CT scan is required to rule out brain metastases if there is clinical suspicion of CNS involvement).
6. Know allergy to egg products or Neomycin (used to prepare ALVAC-CEA/B7.1 vaccines).
7. Previous adverse reaction to receipt of tetanus-toxoid-containing vaccines.
8. Severe toxicity to prior adjuvant chemotherapy, as judged by the investigator.
9. Receipt of a major organ allograft.
10. Receipt of any other investigational product within the last 28 days.
11. Receipt of prior CEA-directed immunotherapy.

ADDITIONAL INFORMATION

For further information, contact Ronda Carlisle, RN, BSN, OCN at (205) 975-2511 or page through the UAB Paging Operator at (205) 934-3411, Pager #6093.