RATIONALE: Vaccines made from a peptide may make the body build an immune response to kill
tumor cells. Combining vaccine therapy with interleukin-2 and/or sargramostim may be a more
effective treatment for solid tumors.
PURPOSE: Phase II trial to study the effectiveness of vaccine therapy plus interleukin-2
and/or sargramostim in treating adults who have metastatic solid tumors.
- Determine whether endogenous cellular immunity to a tumor-specific mutated ras protein
is present in cancer patients.
- Determine whether vaccination with synthetic peptides corresponding to the tumor's ras
mutation with DetoxPC adjuvant, interleukin-2 (IL-2), and/or sargramostim (GM-CSF) can
induce or boost a patient's cellular immunity to that particular mutation.
- Determine the type and characteristics of the cellular immune response generated.
- Determine the tolerance to and toxicity spectrum of such peptides given with DetoxPC
adjuvant along with IL-2 and/or GM-CSF.
- Correlate immune response with tumor response in patients treated with these regimens.
OUTLINE: Patients are assigned to one of three treatment groups.
- Group I (closed to accrual 6/4/01): Patients receive tumor-specific ras peptide vaccine
with DetoxPC subcutaneously (SC) once every 5 weeks for 3 courses. Beginning 4 days
after vaccination, patients receive interleukin-2 (IL-2) SC 5 days a week for 2 weeks.
- Group II (closed to accrual 6/4/01): Patients receive sargramostim (GM-CSF) SC daily
beginning 1 day prior to the vaccination and continuing for 4 days. Patients receive
the vaccination as in group I immediately followed by GM-CSF on day 2. Patients are
vaccinated once every 4 weeks for 3 courses.
- Group III: Patients receive the vaccination and IL-2 as in group I and GM-CSF as in
In all groups, patients receive up to 15 vaccinations in the absence of disease progression.
Patients are followed every 2 months.
PROJECTED ACCRUAL: A maximum of 60 patients (20 per treatment group) will be accrued for
this study within 2-4 years.
- Histologically confirmed solid tumors potentially expressing mutant ras, including
colon, lung, pancreas, thyroid, endometrial, head and neck, testicular,
hepatocellular, and melanoma
- Ras mutations must be one of the following point mutations at codon 12:
- Glycine to cysteine
- Glycine to aspartic acid
- Glycine to valine
- Metastatic disease for which no known chemotherapy or radiotherapy would increase
- Tumor tissue must be available for determination of ras mutation
- No prior CNS metastases
- 18 and over
- ECOG 0-1
- More than 3 months
- WBC at least 2,000/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 2.0 mg/dL
- SGOT/SGPT no greater than 4 times normal
- No hepatitis B or C infection
- Creatinine no greater than 2.0 mg/dL
- No active ischemic heart disease (New York Heart Association class III or IV)
- No myocardial infarction within the past 6 months
- No history of congestive heart failure, ventricular arrhythmias, or other arrhythmias
- No prior allergy to eggs
- No prior autoimmune disease, including the following:
- Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
- Systemic lupus erythematosus, Sjogren's syndrome, or scleroderma
- Myasthenia gravis
- Goodpasture syndrome
- Addison's disease, Hashimoto's thyroiditis, or active Graves' disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No other active malignancy except curatively treated carcinoma in situ of the cervix
or basal cell skin cancer
- No active infection requiring antibiotics
- No medical condition that would preclude study
PRIOR CONCURRENT THERAPY:
- At least 4 weeks since prior immunotherapy and recovered
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy and recovered
- At least 4 weeks since prior steroids and recovered
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy and recovered
- Not specified