Clinical trial NCT00996502
Conditions: Prostate Cancer
Sponsor: Columbia University
Start date: 2006-07-01; Completion date: 2010-03-01
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary objectives of this study are to evaluate the safety and best dose of a regimen including bevacizumab and erlotinib in combination with docetaxel and prednisone. In addition, the investigators wish to evaluate how well these drugs might work against this disease. Bevacizumab and erlotinib are novel drugs that attack the blood vessels supplying the tumor cells and attack a receptor on the tumor cells, respectively. This study has two parts. In the first part of the study, eighteen patients will be enrolled. Patients will receive escalating doses of docetaxel in combination with standard doses of bevacizumab and erlotinib until the safest dose is determined. An additional 37 patients will enter into the second part of the study and all will receive the safest dose. In this part of the study, the effectiveness of this regimen against hormone refractory prostate cancer (HRPC) will be monitored by evaluating prostate-specific antigen (PSA) and objective response of the tumor.

Detailed description:
In this Phase I/Phase II study, the primary objectives are to establish the maximum tolerated dose of docetaxel, erlotinib, bevacizumab, and prednisone in patients with metastatic hormone refractory prostate cancer and to determine the efficacy of this regimen for treatment of metastatic HRPC. In the phase I portion of the study, eligible patients will be enrolled and treated using a "3+3" design. Docetaxel will be started at 55 mg/m2 every cycle (21 days) and dose escalated by 10 mg/m2 at each cohort level. The dose of bevacizumab will be held constant at 15 mg/kg every 3 weeks and erlotinib will be provided at 200 mg PO daily from days 216 as described in previous safety studies. All patients will receive prednisone 5 mg PO bid. Eighteen patients will be treated in the phase I portion. The phase II dose for this combined treatment will be defined as either the highest dosage cohort in which 6 patients are treated and there are less than 3 dose limiting toxicities (DLTs); or the combination of docetaxel, erlotinib, and bevacizumab at the cohort 3 dose level, whichever is the lower dose. Another 37 patients will be enrolled for the phase II study. All patients will receive the phase II recommended dose as determined by the phase I portion of the study.

Arms: arm 1: Bevacizumab, Erlotinib, Docetaxel, Prednisone (dose escalation)

Phase I:

* Cohort 1: 55mg/m2 of Docetaxel on Day 1 of the cycle, 15mg/kg of Bevacizumab every 3 weeks, 200 mg of Erlotinib PO daily days 2-16, 5 mg of Prednisone PO bid
* Cohort 2: 65mg/m2 of Docetaxel on Day 1 of the cycle, 15mg/kg of Bevacizumab every 3 weeks, 200 mg of Erlotinib PO daily days 2-16, 5 mg of Prednisone PO bid
* Cohort 3: 75mg/m2 of Docetaxel on Day 1 of the cycle, 15mg/kg of Bevacizumab every 3 weeks, 200 mg of Erlotinib PO daily days 2-16, 5 mg of Prednisone PO bid
Interventions: intervention 1: Docetaxel intervention 2: Bevacizumab intervention 3: Erlotinib intervention 4: Prednisone
Intervention descriptions: intervention 1: Phase I:

* Cohort 1: 55mg/m2 of Docetaxel on Day 1 of the cycle
* Cohort 2: 65mg/m2 of Docetaxel on Day 1 of the cycle
* Cohort 3: 75mg/m2 of Docetaxel on Day 1 of the cycle intervention 2: 15mg/kg of Bevacizumab every 3 weeks intervention 3: 200 mg of Erlotinib PO daily days 2-16 intervention 4: 5 mg of Prednisone PO bid

Protocol documents: