Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

Clinical trial: Vaccine Therapy Plus Biological Therapy in Treating Adults With Metastatic Solid Tumors

Summary: 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.

Detailed description: OBJECTIVES:
  -  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 group II.
  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.

Eligibility: DISEASE CHARACTERISTICS:
  -  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 survival
  -  Tumor tissue must be available for determination of ras mutation
  -  No prior CNS metastases
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  ECOG 0-1
  Life expectancy:
  -  More than 3 months
  Hematopoietic:
  -  WBC at least 2,000/mm^3
  -  Platelet count at least 100,000/mm^3
  Hepatic:
  -  Bilirubin no greater than 2.0 mg/dL
  -  SGOT/SGPT no greater than 4 times normal
  -  No hepatitis B or C infection
  Renal:
  -  Creatinine no greater than 2.0 mg/dL
  Cardiovascular:
  -  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 requiring therapy
  Immunologic:
  -  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
  Other:
  -  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:
  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:
  -  See Disease Characteristics
  -  At least 4 weeks since prior radiotherapy and recovered
  Surgery:
  -  Not specified

Relevance to patient case: possibly relevant