Study of IL2 in Combination With Zoledronic Acid in Patients With Kidney Cancer

The purpose of this research is to evaluate the antitumor response of low-dose Interleukin-2
in combination with Zoledronic acid on subjects with previously untreated, unresectable
metastatic renal cell carcinoma. Also, the study will assess the tolerability, safety,
pharmacodynamic effects, and immunologic effects of low-dose Interleukin-2 in combination
with Zoledronic acid on angiogenesis inhibition and anti-metastatic potential by measuring
serum/plasma angiogenic/metastatic factor levels and by quantitating changes in cytokine
expression, antigen-specific T-cell immune responses, and peripheral gd T-cell frequency and
function.

Inclusion Criteria:

- Histologically or cytologically confirmed renal cell carcinoma with metastasis.

- Must have measurable disease.

- No prior cytokine, chemotherapy, hormonal, or other immuno-based therapies (including
vaccine or cellular based) for their renal cancer is allowed. No prior use of
bisphosphonates will be allowed. One prior experimental therapy will be permitted as
long as > 4 weeks have passed since last drug administration.

- ECOG performance status 0 or 1

- Adequate cardiac function by history.

- Pulse-oximetry > 92% on room air.

Exclusion Criteria:

- Radiotherapy within 4 weeks prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.

- Known brain metastases

- Any history of an autoimmune disease (ie. psoriasis, inflammatory bowel disease, etc)
must receive clearance by the investigator before being permitted on study due to the
potential worsening of those disorders from IL-

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia.

- History of myocardial infarction or hospitalization for congestive heart failure
within 12 months of enrollment.

- History of prior malignancy (except basal cell carcinoma resected with curative
intent) unless resected or treated with curative intent and disease free for > 5
years.

- Any history of seizures given increased seizure risk with IL-2.

- Organ allograft (transplant) recipients will be excluded given absolute
contraindication with IL-2 therapy.

- Pregnant women are excluded

- Patients on systemic steroids (oral or IV) will not be eligible for the study.