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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

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Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

No

Principal Investigator

John E. Janik, MD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Metabolism Branch;MET

Authority:

United States: Federal Government

Study ID:

CDR0000066874

NCT ID:

NCT00019591

Start Date:

March 1999

Completion Date:

November 2005

Related Keywords:

  • Colorectal Cancer
  • stage III colon cancer
  • stage IV colon cancer
  • stage III rectal cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • Colorectal Neoplasms

Name

Location

Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182