Vaccine Therapy With or Without Interleukin-2 in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer

NCT ID: NCT00019591

Last Updated: 2013-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-03-31
• Study Completion Date: 2005-11-30

Brief Summary

RATIONALE: Vaccines may make the body build an immune response that will kill cancer cells. Combining vaccine therapy with interleukin-2 may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy with or without interleukin-2 in treating patients who have locally advanced or metastatic colorectal cancer.

Detailed Description

OBJECTIVES:

• Determine the frequency of immunologic response in patients with locally advanced or metastatic colorectal cancer treated with ras peptide-pulsed dendritic cell vaccine with or without interleukin-2.
• Determine the tumor response and survival time in patients with metastatic colorectal cancer treated with vaccine plus interleukin-2.
• Determine the time to progression in patients with locally advanced colorectal cancer treated with adjuvant vaccine.

OUTLINE: Patients are assigned to 1 of 2 treatment groups according to extent of disease. Patients with prior locally advanced disease are assigned to treatment group A, while those with metastatic disease are assigned to treatment group B.

• Group A: Patients are vaccinated against influenza on day -6. Patients undergo collection of peripheral blood mononuclear cells (PBMC) on day -4. The PBMC are cultured with sargramostim (GM-CSF) and interleukin-4 for 5 days and CD40 ligand for 24 hours and then pulsed for 2 hours with the appropriate peptide to form a vaccine. Patients receive ras peptide-pulsed dendritic cell vaccine IV over 5 minutes on days 1, 15, 29, 43, and 57.
• Group B: Patients undergo collection of PBMC and receive vaccination as in group A. Patients also receive interleukin-2 subcutaneously on days 2-6 and 9-13.

Treatment in both groups repeats every 2 weeks for up to 5 vaccinations in the absence of disease progression or unacceptable toxicity.

Patients are followed on days 75, 90, 120, and 365.

PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study within 3 years.

Conditions

Colorectal Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

ras peptide cancer vaccine

Intervention Type: BIOLOGICAL

adjuvant therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed locally advanced or metastatic colorectal cancer
• Metastatic disease must be radiologically proven
• HLA-A2-1 positive
• Locally advanced disease must have had prior resection or incomplete resection with poor prognosis
• Locally advanced disease includes:

• Stage III or IV colon cancer (T4 or any T, N2-3, M0)
• Stage III or IV rectal cancer (T4 or T3, N1-3)
• Resectable or unresectable T4 disease after radiotherapy, chemotherapy, and/or surgery
• Absence of measurable disease but more than a 50% chance of recurrence
• Completely resected or locally advanced disease may have had conventional therapy completed within 1-12 months (surgery alone, with or without adjuvant chemotherapy and/or radiotherapy) prior to study entry
• Metastatic disease patients must have bidimensionally measurable disease

• Bone lesions with well-demarcated borders allowed
• Lesions seen only on bone scan, pleural effusions, ascites, and changes in carcinoembryonic antigen are not considered measurable disease

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Lymphocyte count at least 470/mm^3
• Granulocyte count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL*
• SGOT no greater than 4 times upper limit of normal (ULN) (2.5 times ULN for adjuvant patients)*
• Albumin at least 3 g/dL
• No active viral hepatitis
• No evidence of chronic infection due to hepatitis C
• Hepatitis B surface antigen negative NOTE: *Unless due to metastatic disease

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No history of cardiac failure, significant arrhythmias, or coronary artery disease (metastatic disease patients only)

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No prior malignancy with a 50% chance of recurrence within 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No medical or psychiatric condition that would preclude compliance
• No serious medical condition that would preclude apheresis
• No serious infection
• No uncontrolled thyroid disease (metastatic disease patients only)
• Patients with an allergy to eggs are allowed but are not vaccinated against influenza during study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunologic therapy directed at the cellular immune system

Chemotherapy:

• See Disease Characteristics
• Prior chemotherapy for metastatic disease allowed
• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy or anticipated need for chemotherapy for 2 months after vaccinations

Endocrine therapy:

• At least 4 weeks since prior supraphysiologic steroid therapy

Radiotherapy:

• See Disease Characteristics
• Prior radiotherapy for metastatic disease allowed
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Prior surgery for metastatic disease allowed

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

John E. Janik, MD

Role: STUDY_CHAIR

NCI - Metabolism Branch;MET

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

NCI-99-C-0023L

Identifier Type: -

Identifier Source: secondary_id

NCI-T98-0034

Identifier Type: -

Identifier Source: secondary_id

CDR0000066874

Identifier Type: -

Identifier Source: org_study_id

NCT00001794

Identifier Type: -

Identifier Source: nct_alias