17-AAG and Sorafenib in Treating Patients With Unresectable or Metastatic Solid Tumors

PRIMARY OBJECTIVES: I. To recommend a phase II dose for 17AAG (once weekly intravenously for 3 of 4 weeks), in combination with BAY 43-9006 (twice daily orally), by determining the feasibility, safety, dose limiting toxicities and the maximally tolerated dose. SECONDARY OBJECTIVES: I. To evaluate the modulation of pharmacodynamic effects and to investigate the interaction between the two mechanisms of action when used in combination by: Studying surrogate tissue and tumor cell signaling by Western blotting. Evaluating tumor blood flow utilizing dynamic contrast enhanced MRI. II. To study any pharmacokinetic interactions between these two agents. III. To assess preliminary anti-tumor activity of this combination. OUTLINE: This is an open-label, multicenter, dose-escalation study of 17-N-allylamino 17-demethoxygeldanamycin (17-AAG). Patients receive oral sorafenib twice daily on days -14 to 28 in course 1 and on days 1-28 in all subsequent courses. Patients also receive 17-AAG IV over 3 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 5-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 6 patients experience dose-limiting toxicity. After completion of study therapy, patients are followed for 60 days.