Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease

This phase I trial studies the side effects and best dose of bevacizumab and temsirolimus alone or in combination with valproic acid or cetuximab in treating patients with a malignancy that has spread to other places in the body or other disease that is not cancerous. Immunotherapy with bevacizumab and cetuximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as valproic acid, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether bevacizumab and temsirolimus work better when given alone or with valproic acid or cetuximab in treating patients with a malignancy or other disease that is not cancerous.

PRIMARY OBJECTIVES: I. To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of treatment with bevacizumab and temsirolimus in combination and plus valproic acid or cetuximab. SECONDARY OBJECTIVES: I. Preliminary descriptive assessment of anti-tumor efficacy of each combination. II. Preliminary assessment of the pharmacokinetic, pharmacodynamic markers of target inhibition and correlates of response (optional). OUTLINE: This is a dose-escalation study of bevacizumab and temsirolimus. Patients are assigned to 1 of 3 treatment groups. GROUP I: Patients receive temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22; bevacizumab IV over 30-90 minutes on days 1 and 15; and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. GROUP II: Patients receive temsirolimus and bevacizumab as in Group I and valproic acid orally (PO) daily on days 1-7 and 15-21. GROUP III: Patients receive temsirolimus and bevacizumab as in Group I. In all groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.