Clinical trial NCT00027833: Vaccine Therapy and Chemotherapy With or Without Tetanus Toxoid Compared With Chemotherapy Alone in Treating Patients With Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Washington
country: United States
facility: Lombardi Cancer Center
state: District of Columbia
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Portland
country: United States
facility: Earle A. Chiles Research Institute at Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Scranton
country: United States
facility: Scranton Hematology-Oncology
state: Pennsylvania
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Herbert Irving Comprehensive Cancer Center
name: Howard L. Kaufman, MD
role: STUDY_CHAIR
References:
citation: 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.