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

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: FOLFIRI regimen; Biological: ALVAC-CEA-B7.1 vaccine; Biological: tetanus toxoid

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Herbert Irving Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Howard L. Kaufman, MD, Herbert Irving Comprehensive Cancer Center

Publications and helpful links

General Publications

• Kaufman HL, Lenz HJ, Marshall J, Singh D, Garett C, Cripps C, Moore M, von Mehren M, Dalfen R, Heim WJ, Conry RM, Urba WJ, Benson AB 3rd, Yu M, Caterini J, Kim-Schulze S, Debenedette M, Salha D, Vogel T, Elias I, Berinstein NL. Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer. Clin Cancer Res. 2008 Aug 1;14(15):4843-9. doi: 10.1158/1078-0432.CCR-08-0276.

Study record dates

Study Major Dates

• Study Start: December 1, 2001

Study Registration Dates

• First Submitted: December 7, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 6, 2014
• Last Update Submitted That Met QC Criteria: January 3, 2014
• Last Verified: September 1, 2003

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Intestinal Neoplasms; Rectal Diseases; Clostridium Infections; Colorectal Neoplasms; Tetanus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000069082; CPMC-14534; CPMC-BB-IND-9911; FCCC-01015; APL-COL13; NCI-G01-2033