A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer
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
To evaluate the efficacy of the combination
To evaluate overall survival of the enrolled patients and the toxicity profile of the
To evaluate circulating prostate cancer cells before and after drug administration
To measure circulating apoptotic endothelial cells before and after drug administration and
to correlate with efficacy of the combination
To determine whether there are changes in the molecular markers of angiogenesis before and
after administration of the combination
To analyze the patients' genotype with regard to genes involved in transport and
metabolization of these agents to correlate that with efficacy
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
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
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess safety of Lenalidomide at approved dosing schedule when combined with Docetaxel, Bevacizumab, and Prednisone in patients with mCRPC as measured by less than 25% Grade 4 toxicity and evaluation of the efficacy of the drug combination.
William L Dahut, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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