Phase I/II Study of Docetaxel, Prednisone and Pazopanib in Men With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) and Poor-Risk Factors
This Phase I/II 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 tolerated with 0-1 Dose Limiting Toxicity (DLT)
experienced in six patients. Patients from all risk strata will be allowed onto the Phase I
portion.
Once the MTD is established the investigators will perform a randomized Phase II study in
men with intermediate or poor risk CRPC. Clinical efficacy in this patient population will
be compared to that of patients treated with DPP to DP for PFS, overall survival (OS),
objective response rates (ORR), Prostate Specific Antigen (PSA) kinetics and pain response.
Patients will be treated for up to a maximum of 1 year with the combination, after which
patients will be allowed to continue on pazopanib alone.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Number and Percent of Participants with Adverse Events as a Measure of Safety and Tolerability; Number and Percent of participants who have disease progression
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. The primary objective for the phase II study is to measure the anti-tumor activity of pazopanib, docetaxel, and prednisone compared to placebo, docetaxel, and prednisone as assessed by progression free survival.
3 years
Yes
Daniel J George, MD
Principal Investigator
Duke Cancer Institute
United States: Food and Drug Administration
Pro00026577
NCT01385228
June 2011
December 2016
Name | Location |
---|---|
Duke Cancer Institute | Durham, North Carolina 27710 |
The University of Chicago | Chicago, Illinois 60637 |