The primary purpose is to define the safety and tolerability of docetaxel/prednisone in combination with pazopanib (DPP) in men with metastatic Castration Resistant Prostate Cancer (mCRPC).
This Phase I study will consist of a dose escalation portion which includes a dose escalation phase of 10 dose levels: (1a) docetaxel 60 mg/m2, pazopanib 400 mg daily, prednisone 5 mg BID; (2a) docetaxel 75 mg/m2, pazopanib 400 mg daily, prednisone 5 mg BID; and (3a) docetaxel 75 mg/m2, pazopanib 600 mg daily, prednisone 5 mg BID; (4a) docetaxel 75mg/m2, pazopanib 800 mg daily, (5a) docetaxel 75mg/m2, pazopanib 1000mg daily, prednisone 5 mg; (1b) docetaxel 60 mg/m2, pazopanib 400 mg daily x 17 days, prednisone 5 mg BID; (2b) docetaxel 75 mg/m2, pazopanib 400 mg daily x 17 days, prednisone 5 mg BID; and (3b) docetaxel 75 mg/m2, pazopanib 600 mg daily x 17 days, prednisone 5 mg BID; (4b) docetaxel 75mg/m2, pazopanib 800 mg daily x 17 days, (5b) docetaxel 75mg/m2, pazopanib 1000mg daily x 17 days, prednisone 5 mg. If the investigators see \> 1 dose limiting toxicity (DLT) at Dose level 3 then the investigators would investigate docetaxel 75 mg/m2, pazopanib 600 mg daily, prednisone 5 mg BID (Dose level 3a). If \< 1 DLT are seen at Dose level 3 and Pharmacokinetic (PK) analysis is complete and acceptable, then the investigators will proceed to dose level 4) docetaxel 75 mg/m2, pazopanib 1000 mg daily, prednisone 5 mg BID. The investigators will dose escalate in a classic 3+3 design. The maximum tolerated dose (MTD) will be defined as the highest dose level that does not result in 2 or more dose limiting toxicities (DLTs). A dose expansion at the MTD of 10-15 patients (up to a total of 36 patients) will be accrued in order to further describe the safety profile.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Dose Level "Xa" - daily administration of pazopanib on days 1 through 21 starting at 400mg with a maximum dose of 1000mg.
Docetaxel given IV on Day 1 starting dose 60mg/m2 increase to 75mg/m2
Dose Level "Xb" - daily administration of pazopanib on days 3 through 19 starting at 400mg with a maximum dose of 1000mg.
The University of Chicago
Chicago, Illinois, United States
Duke Cancer Institute
Durham, North Carolina, United States
Number and Percent of Participants with Adverse Events as a Measure of Safety and Tolerability
The primary objective for the phase I study is to assess the safety and tolerability of pazopanib, docetaxel, and prednisone given in combination in patients with metastatic castration resistant prostate cancer.
Time frame: 15 months
Establish the maximum tolerated dose
Determine the dose levels of pazopanib and docetaxel that are the most tolerated.
Time frame: 15 months
Establish the optimal dosing schedule
Establish the optimal dosing schedule for the combination of docetaxel, prednisone and pazopanib
Time frame: 15 months
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5mg Prednisone given twice daily days 1-21.