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

Colorectal Cancer Clinical Trial

Official title:

A Phase I/II Trial of Vaccination With Mutant Ras Peptide-Pulsed Dendritic Cells in the Treatment of HLA A2.1 Positive Patients With Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00019591
• Other study ID #: CDR0000066874
• Secondary ID: NCI-99-C-0023LNC
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 11, 2001
• Last updated: June 19, 2013
• Start date: March 1999
• Est. completion date: November 2005

Study information

• Verified date: November 2005
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00001794

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• aldesleukin

• ras peptide cancer vaccine

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate every 3 months for up to a year after completion of study treatment			No