Patient case: 49-year-old male with melanoma; genetic feature: extensive tumor infiltrating lymphocytes

Clinical trial: Genistein and Interleukin-2 in Treating Patients With Metastatic Melanoma or Kidney Cancer

Summary: RATIONALE: Genistein may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Interleukin-2 may stimulate the white blood cells, including natural killer cells, to kill melanoma or kidney cancer cells. Giving genistein together with interleukin-2 may kill more tumor cells.
  PURPOSE: This phase II trial is studying how well giving genistein together with interleukin-2 works in treating patients with metastatic melanoma or kidney cancer.

Detailed description: OBJECTIVES:
  Primary
  -  Measure the differences in peak and duration of the expansion of circulating CD4-positive, CD8-positive, and CD4-, CD25-, and CD56-positive cells (dim and bright) at different time points during therapy with interleukin-2 (IL-2) alone and plus genistein in patients with metastatic malignant melanoma or renal clear cell carcinoma.
  Secondary
  -  Evaluate the differences in peripheral blood mononuclear cell gene expression following high-dose IL-2 with and without genistein and compare to baseline.
  -  Determine the overall response rate (partial and complete) in patients treated with these regimens.
  -  Determine the safety and toxic effects of these regimens in these patients.
  -  Determine the time to progression in patients treated with these regimens.
  OUTLINE: This is a pilot study.
  Patients receive high-dose interleukin-2 IV over 15 minutes twice daily on days 1 and 15 and 3 times daily on days 2-5 and 16-19. Patients also receive oral genistein twice daily on days 10-19.
  After completion of study treatment, patients are followed periodically.
  PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Documented histologically confirmed malignant melanoma or renal clear cell carcinoma
  -  Metastatic disease
  -  At least 1 measurable lesion that can be accurately measured in at least one dimension with longest diameter > 20 mm using conventional techniques OR > 10 mm with spiral CT scan
  -  If the measurable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology
  -  Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules or palpable lymph nodes)
  -  The following are considered non-measurable lesions:
  -  Bone lesions
  -  Leptomeningeal disease
  -  Ascites
  -  Pleural/pericardial effusion
  -  Inflammatory breast disease
  -  Lymphangitis cutis/pulmonis
  -  Cystic lesions
  -  Abdominal masses that are not confirmed and followed by imaging techniques
  -  No CNS metastases by CT scan or MRI
  PATIENT CHARACTERISTICS:
  -  ECOG performance status < 2
  -  Life expectancy ≥ 4 months
  -  Serum creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
  -  Bilirubin normal
  -  Platelets > 100,000/mm³
  -  WBC > 3,500/mm³
  -  No evidence of congestive heart failure
  -  No symptom of coronary artery disease
  -  No serious cardiac arrhythmias
  -  A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment if any cardiac symptoms present (patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study)
  -  Adequate pulmonary reserve
  -  FEV_1 > 75% of predicted
  -  Not pregnant or nursing
  -  Fertile patients must use effective contraception
  -  Negative pregnancy test
  -  No known HIV-positive patients
  -  No evidence of active infection requiring antibiotic therapy
  -  No contraindication to treatment with pressor agents
  -  No significant medical disease which, in the opinion of the investigator, may interfere with completion of the study
  -  No history of another malignancy other than basal cell skin cancer within 5 years
  PRIOR CONCURRENT THERAPY:
  -  Recovered from all toxic effects of prior therapy
  -  No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of the study treatment
  -  No systemic corticosteroids in the 4 weeks prior to treatment
  -  No previous investigational agent within 4 weeks prior to the start of the study
  -  No prior interleukin-2 therapy
  -  No organ allografts allowed
  -  No concurrent radiotherapy, chemotherapy, or immunotherapy
  -  No concurrent corticosteroids
  -  No concurrent chronic medication for asthma

Relevance to patient case: not relevant