A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer
- Prednisone and docetaxel have been used successfully in treating patients with prostate cancer, either when used alone or in combination with other agents. Researchers believe that these anticancer effects can be increased by giving them in this specific combination.
- A previous study at the National Cancer Institute combined docetaxel and prednisone with bevacizumab and thalidomide. The results of this study were promising; however, most patients in the study required a dose reduction of thalidomide because of its side effects.
- Lenalidomide, a drug similar to thalidomide, may have less severe side effects. Based on previous studies, lenalidomide is well tolerated in patients with solid tumors when used alone or in combination with docetaxel, and it may be a good substitute for thalidomide.
- To determine if lenalidomide is an appropriate and effective substitute for thalidomide in treating prostate cancer.
- To evaluate the safety and effectiveness of bevacizumab, lenalidomide, docetaxel, and prednisone as a prostate cancer treatment, and to study any side effects.
- Men 18 years of age and older who have been diagnosed with metastatic prostate cancer that has not responded to standard treatment, including surgical removal of the testicles or treatment with androgen (sex-hormone) suppressing drugs.
- Participants will have a complete medical history and physical examination before beginning the study.
- Patients will be treated with 21-day cycles with a combination of four drugs:
- (1) Docetaxel, which will be given into a vein for 60 minutes on the first day of each 21-day cycle. Patients will take dexamethasone (a steroid agent) before and after taking docetaxel.
- (2) Prednisone, which will be taken by mouth daily.
- (3) Bevacizumab, which will be given through a vein over 30 to 90 minutes on the first day of each 21-day cycle following the infusion of docetaxel.
- (4) Lenalidomide, which will be taken by mouth during the first 2 weeks of each 21-day cycle. The dose of lenalidomide may be adjusted if side effects develop.
- Patients will also receive enoxaparin, a subcutaneous injection administered daily, to prevent blood clots and/or pegfilgrastim, a subcutaneous injection on day 2 of each cycle, to improve white blood cell counts, as directed by researchers.
Metastatic Prostate Cancer
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer|
- Safety of adding lenalidomide to a regimen containing bevacizumab,docetaxel and prednisone [ Time Frame: Dose Limiting Toxicity ]
- Efficacy of lenalidomide with this drug regimen [ Time Frame: Disease progression ]
- Evaluate overall survival of patients studied [ Time Frame: 3-4 years ]
- Evaluate the effects of the combination on the immune system before and after drug administration [ Time Frame: 3-4 years ]
- Analyze the patients genotype with regard to genes involved intransport and metabolization of these agents to correlate thatwith efficacy [ Time Frame: 3-4 years ]
- Evaluate changes in circulating apoptotic endothelial cells before and after drug administration [ Time Frame: 3-4 years ]
- Determine whether there are changes in the molecular markers of angiogenesis (including, but not limited to serum and urine VEGF) before and after administration of docetaxel, prednisone,lenalidomide and bevacizumab [ Time Frame: 3-4 years ]
- Evaluate the toxicity profile of the four-drug combination [ Time Frame: 3-4 years ]
|Study Start Date:||July 16, 2009|
|Estimated Study Completion Date:||January 1, 2019|
|Estimated Primary Completion Date:||January 1, 2018 (Final data collection date for primary outcome measure)|
Experimental: Single Arm
A two dose level escalation of Lenalidomide from 15mg to 20mg to 25mg- standard 3+3 dose escalationapproach in combination with docetaxel, Bevacizumab and prednisone.
15 mg/kg cycle 1 day 1, repeated every 21 daysDrug: Lenalidomide
Once daily days 1-14 of every 21Drug: Docetaxel
75 mg/m2 IV over 60 minutes on cycle 1 day 1, repeated every 21 days (a 3-week cycle)Drug: Prednisone
10 mg orally every day
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00942578
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Ravi A Madan, M.D.||National Cancer Institute (NCI)|