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

Kidney Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00276835
• Other study ID #: NU 04V1
• Secondary ID: NU-04V1CHIR-NU-0
• Status: Completed
• Phase: Phase 0
• First received: January 12, 2006
• Last updated: April 8, 2015
• Start date: November 2005
• Est. completion date: January 2014

Study information

• Verified date: April 2015
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 2014
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms
• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• High-dose interleukin-2
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)

Dietary Supplement:
• genistein
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)

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Circulating plasma levels of TGF-beta		Prior to and at end of treatment	No