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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: aldesleukin; Procedure: adjuvant therapy; Biological: ras peptide cancer vaccine

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center

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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate every 3 months for up to a year after completion of study treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: John E. Janik, MD, NCI - Metabolism Branch;MET

Study record dates

Study Major Dates

• Study Start: March 1, 1999
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 19, 2013
• Last Verified: November 1, 2005

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; stage III colon cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Aldesleukin
• Other Study ID Numbers: CDR0000066874; NCI-99-C-0023L; NCI-T98-0034