Phase I, Pharmacokinetic and Pharmacodynamic Study of BAY 43-9006 (Sorafenib) in Combination With CCI-779 (Temsirolimus) in Advanced Solid Malignancies
I. To characterize the safety and the toxicities of BAY 43-9006 (sorafenib) administered
continuously twice daily by oral route in combination with CCI-779 (temsirolimus)
administered intravenously once weekly in advanced solid malignancies.
II. To determine the maximum-tolerated dose (MTD) and recommended dose for the phase II
study (RD) of this regimen.
III. To describe the pharmacokinetic behavior of BAY 43-9006 (sorafenib) and CCI-779
(temsirolimus) when combined.
I. To evaluate the relationship between pharmacokinetic (PK) parameters of exposure and drug
effect on biological surrogates of proliferation, cell survival, differentiation and
angiogenesis in peripheral blood mononuclear cells (PBMCs) and tumor tissue where the tumor
is accessible for biopsy.
II. To analyze the biologic effects of BAY 43-9006 and CCI-779 on downstream targets of the
P13K/Akt/mTOR and Raf signaling pathways.
III. To evaluate preliminary antitumor activity of the combination.
OUTLINE: This is an open-label, dose-escalation study of temsirolimus.
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. They also receive
oral sorafenib* twice daily starting on day 8 of course 1. Treatment repeats every 4 weeks
in the absence of disease progression or unacceptable toxicity.
NOTE: *On the days of the temsirolimus infusion, temsirolimus should be taken concurrently
with the morning dose of sorafenib.
Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Up to 12 patients are treated at the MTD.
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerable dose (MTD) and recommended dose for phase II determined by dose-limiting toxicities (DLT) graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
United States: Food and Drug Administration
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