Trial Information

A Phase I Study of Bolus High Dose Interleukin-2 With Sorafenib (BAY 43-9006) in Patients With Unresectable or Metastatic Clear Cell Renal Carcinoma (RCC) and Metastatic Melanoma

Rationale: Previous research indicates that high dose aldesleukin produces tumor regression
through upregulation of the patients' immune system. Research suggests that sorafenib
directly targets tumors by inhibiting angiogenic activity with possibly some cytotoxicity.
Angiogenic refers to the formation of new blood vessels that support tumor growth.
Cytotoxicity is the measurement of a chemical's ability to damage or kill cancer cells.
Researchers have hypothesized that the complementary ways aldesleukin and sorafenib work,
and their non-overlapping toxicity profiles, may create a reasonable combination for the
treatment of metastatic renal cell carcinoma and metastatic melanoma. The current Phase I
study will evaluate toxicity in patients through assessing various dose levels of sorafenib
in combination with aldesleukin.

Purpose: The primary objective is to determine the maximum tolerated dose and characterize
the toxicity of high dose aldesleukin and sorafenib in patients with unresectable or
metastatic clear cell renal carcinoma and metastatic melanoma. Secondary objectives include
determining progression free survival in patients, evaluating in a preliminary manner
response rates, and assessing other measurements in study participants.

Treatment: Study participants will be given bolus high dose aldesleukin and sorafenib.
Aldesleukin will be provided through intravenous infusions on days 1 through 5. Each 5 day
treatment is considered a cycle. The second cycle of aldesleukin will start on day 15. Two
cycles are considered 1 course. All study participants will be given the same dose level of
aldesleukin. No dose reductions will be permitted. Sorafenib will then be administered on
day 29. Since this study will assess the maximum tolerated dose of sorafenib, some study
participants will receive different amounts of this drug compared to others depending upon
when each individual enrolls in the study. Each group of 3 to 6 study participants will
receive a higher dose of sorafenib until the maximum tolerated dose is established.
Imagining studies will be performed to determine response to treatment during week 12. If
the patient has stable or responding disease, a second course will be administered on the
same schedule. Patients without disease response will be given one additional course of
aldesleukin past maximal response. When it is decided that no further aldesleukin will be
provided to patients, sorafenib at the Food and Drug Administration approved dose may be
continued until there is a lack of clinical benefit or intolerable side effects develop.
Several tests and exams will be given throughout the study to closely monitor patients.