Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy and Chemotherapy With or Without Tetanus Toxoid Compared With Chemotherapy Alone in Treating Patients With Metastatic Colorectal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI, Pharmaceutical / Industry CPMC-14534 CPMC-BB-IND-9911, FCCC-01015, APL-COL13, NCI-G01-2033, NCT00027833

Objectives

1. 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.
2. Determine whether tetanus toxoid enhances the immune response in patients treated with the vaccine and chemotherapy.

Entry Criteria

Disease Characteristics:

• Histologically confirmed metastatic colorectal adenocarcinoma



• No clinically active CNS metastases

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 6 months

Hematopoietic:

• Lymphocyte count at least 1,000/mm³
• Granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

A total of 90 patients (30 per treatment arm) will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Howard Kaufman, MD, Protocol chair		Ph: 212-342-6042 Email: hlk2003@columbia.edu

Registry Information
Official Title		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
Trial Start Date		2001-12-31
Registered in ClinicalTrials.gov		NCT00027833
Date Submitted to PDQ		2001-10-17
Information Last Verified		2003-09-08
NCI Grant/Contract Number		CA13696