Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed Over 18 NCI NCI-99-C-0023L NCI-T98-0034, NCT00019591, T98-0034

Special Category: NIH Clinical Center trial

Objectives

1. 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.
2. Determine the tumor response and survival time in patients with metastatic colorectal cancer treated with vaccine plus interleukin-2.
3. Determine the time to progression in patients with locally advanced colorectal cancer treated with adjuvant vaccine.

Entry 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

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

Patient Characteristics:

Age:

• Over 18

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Lymphocyte count at least 470/mm³
• Granulocyte count at least 1,000/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

Outcomes

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

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

John Janik, MD, Protocol chair		Ph: 301-402-2913 Email: janikj@mail.nih.gov

Registry Information
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
Trial Start Date		1999-03-29
Registered in ClinicalTrials.gov		NCT00019591
Date Submitted to PDQ		1999-01-25
Information Last Verified		2005-11-29

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