A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer
|ClinicalTrials.gov Identifier: NCT00942578|
Recruitment Status : Completed
First Posted : July 21, 2009
Last Update Posted : August 2, 2017
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Prostate Cancer||Drug: Bevacizumab Drug: Lenalidomide Drug: Docetaxel Drug: Prednisone||Phase 2|
Hide Detailed Description
The dual antiangiogenic therapy with bevacizumab and thalidomide in combination with docetaxel and prednisone (ATTP) is highly active in patients with metastatic castration resistant prostate cancer (mCRPC), associated with unprecedented results (90% patients had PSA declines of greater than or equal to 50% and 64% ORR in measurable disease).
Most patients in the ATTP trial required dose reduction due to thalidomide toxicities.
Lenalidomide, an analogue of thalidomide, possesses both antiangiogenesis and inhibition of TNF-alpha, but has a favorable toxicity profile. Lenalidomide is well tolerated in patients with solid tumors when used alone or in combination with docetaxel.
To preserve the efficacy of ATTP and to potentially reduce toxicity, lenalidomide may be a good substitute for thalidomide.
To assess if lenalidomide at its approved dosing schedule can be safely combined with docetaxel, bevacizumab, and prednisone in patients with mCRPC (less than 25% Grade 4 toxicity)
To evaluate the efficacy of the combination
Patients with progressive mCRPC who have not received any chemotherapy or antiangiogenic therapy for mCRPC
A single-stage Phase 2 study, with an early stopping rule for excessive toxicity: the goal is to enroll 45 patients at the 25-mg dose level of lenalidomide. However, if 7 in the first 18 or fewer patients receiving lenalidomide at 25 mg develop grade 4 non-hematologic toxicity at anytime during study, no further patients will be enrolled. With respect to the stopping rule, a grade 4 hematologic toxicity will be considered if the episode has lasted for greater than or equal to 5 days. Grade 4 lymphopenia of any duration will not be counted. If less than 7 of the first 18 patients experience the above level of toxicity, accrual will continue until 45 patients have been enrolled at the 25 mg dose level of lenalidomide.
A run-in phase with lenalidomide at 15 mg will be conducted in the first three patients and at 20mg for the next three patients for assessing its tolerability within the combination prior to dosing at 25 mg thereafter.
An expansion cohort of a lower dose of lenalidomide (15 mg) in combination with docetaxel and and Avastin will be conducted to asses if this lower dose of lenalidomide could have similar efficacy with less toxicity.
Treatment Schema of ART-P
Dex -Dexamethasone 8 mg. po 12 hours pre, 3 hours pre, and 1 hour pre infusion of docetaxel (patients who were on prior regimen which included a lower dose of decadron and did not have a reaction do not have to increase their decadron to the 8 mg dose)
Len - Lenalidomide 25 mg po, days 1-14. Lenalidomide 15 mg and 20mg for the proposed run-in phase. Lenalidomide 15 mg for the expansion cohort.
Doc - Docetaxel 75 mg/m2 IV
Bev - Bevacizumab 15 mg/kg IV
Pre - Prednisone 10 mg PO daily throughout cycle
E - Enoxaparin given SQ daily based on weight (see dosing chart in section 4.2)
Peg - Pegfilgrastim 6mg SQ given at least 24 hours after docetaxel administration
Baseline screening evaluations are to be conducted within 15 days prior to protocol enrollment. Baseline scans and x-rays must be performed 4 weeks prior to protocol enrollment. Patients must be evaluated at the NCI clinic each cycle for treatment continuation. Staging scans will be performed after the first 2 cycles of treatment and then every three cycles. All follow-up evaluations can be done on the last week of the prior cycle.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||63 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer|
|Study Start Date :||July 16, 2009|
|Actual Primary Completion Date :||July 31, 2017|
|Actual Study Completion Date :||July 31, 2017|
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
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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)|