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

Study Overview
=================
Brief 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.

Official Title
-----------------
A Pilot Study of the Effect of Genistein in Combination With High-Dose Interleukin-2 on Cell Expansion and Gene Expression in Patients With Metastatic Melanoma or Renal Cell Carcinoma

Conditions
-----------------
Kidney Cancer, Melanoma (Skin)

Intervention / Treatment
-----------------
* Biological: High-dose interleukin-2
* Dietary Supplement: genistein


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genistein and Interleukin-2<br> | Biological: High-dose interleukin-2<br>* Administered days 1-5, and 15-19; the patient will receive 600,000 IU/kg IL-2 by intravenous infusion over 15 minutes every 8 hours (on day 1 and day 15, patients will receive a maximum of 2 doses per day; on all other days in the cycle patients will receive a maximum of 3 doses per day)<br>* Other names: Proleukin;Dietary Supplement: genistein<br>* Starting on day 10 and continuing through day 19, genistein will be administered orally at a dose of 600mg/day in two divided doses (i.e. 300mg po bid x 10 days)<br>* Other names: isoflavone;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in peak and duration of the expansion of circulating CD4+, CD8+, and CD4+, CD25+, and CD56+ cells (dim and bright) |  | Days 1, 8, 10, 15, 22, and 24 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating plasma levels of TGF-beta |  | Prior to and at end of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
clear cell renal cell carcinoma, recurrent renal cell cancer, stage IV renal cell cancer, recurrent melanoma, stage IV melanoma