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Phase I Pilot Study of Vaccine Therapy With Tumor-Specific Mutated Ras Peptides in the Adjuvant Setting in Patients With Colorectal, Pancreatic, or Lung Cancer


Phase 1
18 Years
N/A
Not Enrolling
Both
Recurrent Colon Cancer, Extensive Stage Small Cell Lung Cancer, Stage III Pancreatic Cancer, Stage III Rectal Cancer, Limited Stage Small Cell Lung Cancer, Recurrent Pancreatic Cancer, Recurrent Rectal Cancer, Stage III Non-Small Cell Lung Cancer, Stage I Pancreatic Cancer, Stage II Non-Small Cell Lung Cancer, Stage IVB Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Colon Cancer, Stage IVA Pancreatic Cancer

Thank you

Trial Information

Phase I Pilot Study of Vaccine Therapy With Tumor-Specific Mutated Ras Peptides in the Adjuvant Setting in Patients With Colorectal, Pancreatic, or Lung Cancer


OBJECTIVES: I. Determine whether endogenous cellular or humoral immunity to a
tumor-specific mutated ras protein is present in patients with colorectal, pancreatic, or
lung cancer.

II. Determine whether vaccination with a synthetic peptide corresponding to the tumor's ras
mutation combined with Detox-B adjuvant can induce or boost cellular immunity to that
particular mutation in this patient population.

III. Determine the type and characteristics of any cellular immunity generated in these
patients treated with this regimen.

IV. Determine the tolerance and toxicity spectra of such peptides given with Detox-B
adjuvant in these patients.

V. Determine the immune response associated with each peptide dose in these patients.

VI. Assess any tumor response that may occur with treatment in these patients treated with
this regimen.

PROTOCOL OUTLINE: This is a dose-escalation study. Patients receive tumor-specific mutated
ras peptide combined with Detox-B adjuvant subcutaneously monthly for 3 months. Treatment
continues in the absence of disease progression or unacceptable toxicity. Patients with
stable or responding disease or with a specific immunologic response may receive 3
additional monthly vaccinations.

Cohorts of 3-6 patients receive escalating doses of tumor-specific mutated ras peptide
combined with Detox-B adjuvant until the maximum tolerated dose (MTD) is determined. The
MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience
dose-limiting toxicity.

PROJECTED ACCRUAL:

A total of 33 patients (12 in the adjuvant setting) will be accrued for this study within 12
months.

Inclusion Criteria


1. Histopathologically confirmed diagnosis of Langerhans cell histiocytosis according to
the criteria defined by the Histiocyte Society

- Demonstration of CD1a antigenic determinants on the surface of lesional cells
(by immunocytology or immunohistology) or Birbeck granules in lesional cells by
electron microscopy

2. Considered at risk or low risk according to the following criteria:

1. Multi-system at risk disease, defined as involvement of one or more risk organs
(i.e., hematopoietic system, liver, spleen, or lungs)

- No single-system lung involvement

2. Multi-system low-risk disease

- Multiple organs involved but without involvement of risk organs

3. Single-system disease

- Multifocal bone disease (i.e., lesions in 2 or more different bones)

- Localized special site involvement, such as CNS-risk lesions with
intracranial soft tissue extension or vertebral lesions with intraspinal
soft tissue extension

- Vault lesions are not regarded as CNS-risk lesions

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-- Histologically documented solid tumor potentially expressing
mutant ras Stage II/III adenocarcinoma of the lung following surgery or radiotherapy
Limited or extensive small cell lung cancer in complete remission Dukes' C colorectal
cancer following appropriate adjuvant chemotherapy Fully resected recurrent colorectal
carcinoma Fully resected pancreatic carcinoma Tumor tissue available for determination of
ras mutation Paraffin block or fresh tissue Specific point mutation in codon 12 required,
which includes: Glycine to cysteine Glycine to aspartic acid Glycine to valine Tumor
tissue available for preparation of a tumor cell line and tumor or lymph node tissue for
expansion of tumor infiltrating lymphocytes for in vitro laboratory studies preferred No
history of CNS metastases --Prior/Concurrent Therapy-- Biologic therapy: At least 4 weeks
since prior immunotherapy and recovered Chemotherapy: See Disease Characteristics At least
4 weeks since prior chemotherapy and recovered Endocrine therapy: At least 4 weeks since
prior steroids and recovered Radiotherapy: At least 4 weeks since prior radiotherapy and
recovered Surgery: See Disease Characteristics Not specified --Patient Characteristics--
Age: Over 18 Performance status: ECOG 0-1 Life expectancy: More than 3 months
Hematopoietic: WBC at least 3,000/mm3 Lymphocyte count at least 600/mm3 Platelet count at
least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL ALT and AST no greater than
4 times normal Hepatitis B and C surface antigen negative Renal: Creatinine no greater
than 2.0 mg/dL Cardiovascular: No active ischemic heart disease (New York Heart
Association class III/IV) No myocardial infarction within 6 months No history of
arrhythmia No clinical symptoms suggesting cardiac insufficiency Pulmonary: No clinical
symptoms suggesting pulmonary insufficiency Immunologic: Responsive to anergy skin testing
with mumps, trichophyton, or candida antigens HIV negative No autoimmune disease, e.g.:
Systemic lupus erythematosus Multiple sclerosis Ankylosing spondylitis Other: No active
infection requiring antibiotics No history of malignancy except curatively treated basal
cell skin carcinoma or curatively treated carcinoma in situ of the cervix Not pregnant or
nursing Negative pregnancy test Fertile patients must use effective contraception

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Samir N. Khleif

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

CDR0000063475

NCT ID:

NCT00019006

Start Date:

March 1995

Completion Date:

Related Keywords:

  • Recurrent Colon Cancer
  • Extensive Stage Small Cell Lung Cancer
  • Stage III Pancreatic Cancer
  • Stage III Rectal Cancer
  • Limited Stage Small Cell Lung Cancer
  • Recurrent Pancreatic Cancer
  • Recurrent Rectal Cancer
  • Stage III Non-Small Cell Lung Cancer
  • Stage I Pancreatic Cancer
  • Stage II Non-Small Cell Lung Cancer
  • Stage IVB Pancreatic Cancer
  • Stage II Pancreatic Cancer
  • Stage III Colon Cancer
  • Stage IVA Pancreatic Cancer
  • adult solid tumor
  • body system/site cancer
  • cancer
  • colon cancer
  • colorectal cancer
  • extensive stage small cell lung cancer
  • gastrointestinal cancer
  • genetic condition
  • limited stage small cell lung cancer
  • lung cancer
  • non-small cell lung cancer
  • pancreatic cancer
  • rectal cancer
  • recurrent colon cancer
  • recurrent pancreatic cancer
  • recurrent rectal cancer
  • small cell lung cancer
  • solid tumor
  • stage I pancreatic cancer
  • stage II non-small cell lung cancer
  • stage II pancreatic cancer
  • stage III colon cancer
  • stage III non-small cell lung cancer
  • stage III pancreatic cancer
  • stage III rectal cancer
  • stage IV pancreatic cancer
  • stage IVA pancreatic cancer
  • stage IVB pancreatic cancer
  • stage, colon cancer
  • stage, non-small cell lung cancer
  • stage, pancreatic cancer
  • stage, rectal cancer
  • stage, small cell lung cancer
  • thorax/respiratory cancer
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Pancreatic Neoplasms
  • Small Cell Lung Carcinoma

Name

Location

Medicine BranchBethesda, Maryland  20892