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

Northwestern University

Status and phase

Completed

Early Phase 1

Conditions

Melanoma (Skin)

Kidney Cancer

Treatments

Biological: High-dose interleukin-2

Dietary Supplement: genistein

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00276835

CHIR-NU-04V1

NU-04V1

NU-IRB-0310-083

NU 04V1

Details and patient eligibility

About

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.

Full 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.

Enrollment

15 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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