A Phase 1 Trial of the Combination of Perifosine and Docetaxel With or Without Prednisone

This is a phase 1, open-label trial of perifosine and docetaxel with or without prednisone in patients with malignancies for whom single agent docetaxel is a reasonable treatment option. All patients will receive docetaxel at a dose of 75 mg/m2 on day 8 of a 21-day cycle either without (Arm A) or with prednisone 5 mg bid on days 1 - 21 (Arms B and C). (Patients on all arms will receive premedication with dexamethasone around the time of docetaxel administration either as described in the product insert for arm A or as used in prior prostate cancer phase III studies for arm B and C. The 1st cohort of patients on Arm A and Arm B will receive perifosine orally at a dose of 50 mg per day for the first 14 days of the 21-day cycle. On each arm, the perifosine dose will be escalated in subsequent groups to 50 mg bid and then 50 mg tid as tolerated. Alternating cohorts of 3 patients will be entered first to Arm A and then to Arm B. At the completion of arms A and B, 3 cohorts of patients will be entered who will receive perifosine weekly at doses of 900, 1200 and 1500 mg. The total dose will be divided into 300 mg doses which will be delivered at least 4 hours apart. The perifosine dose escalation for each arm will be performed separately according to the following algorithm. For each arm, a maximum tolerated dose (MTD) will be defined as a dose that can be given without grade 3/4 non-hematologic toxicity in more than 1/3 patients. If 2/3 patients in any cohort encounter a grade 3/4 non-hematologic toxicity, an additional 3 patients will be added. If the dose is intolerable for >3/6 patients then the previous dose level will be declared the MTD for that arm.