OBJECTIVE: To conduct a phase II trial of the combination of @entity3003 , @entity229 and @entity2239 in metastatic castrate resistant @entity263 (mCRPC) as @entity3470 inhibition can overcome resistance to chemotherapy in @entity263 . METHODS: @entity1 with progressive mCRPC pretreated with @entity1205 based regimen were eligible. Performance status of 0-1 and adequate bone marrow, @entity177 were required. Primary endpoint was time to progression. Treatment consisted of @entity3003 (starting dose equal to area under the curve (AUC of 5) intravenously every 21 days along with oral @entity2239 5 mg once daily and @entity229 5 mg twice daily. RESULTS: 26 @entity1 were enrolled with median age of 69 years with 8 @entity1 of African American origin. Grade 3 or 4 @entity882 or @entity1398 in 4 of 6 initial @entity1 , required dose adjustment of @entity3003 to AUC of 4 for subsequent @entity1 . There were no PK interactions between @entity3003 and @entity2239 . The median time to progression was 2.5 months (90% confidence interval [CI] 1.8-4.3 months) and median overall survival was 12.5 months (90% CI 7.7-18.7 months). 8 of 10 @entity1 that demonstrated positive nuclear pAKT staining on immunohistochemistry progressed within 9 weeks, whereas two @entity1 with negative staining continued without progression for prolonged durations of 30 and 48 weeks. @entity10622 gene mutations did not correlate with clinical outcome. CONCLUSIONS: The addition of the @entity19213 inhibitor @entity2239 , to @entity3003 demonstrated minimal clinical efficacy in metastatic @entity263 . pAKT testing warrants further evaluation as a predictive marker of response to @entity2239 therapy.

Phase II trial of @entity3003 , @entity2239 and XXXX in metastatic castrate resistant @entity263 pretreated with @entity1205 chemotherapy: A @entity263 Clinical Trial Consortium Study.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity3003 :: ('MESH:D016190', 'Chemical') :: ['carboplatin'] @entity229 :: ('MESH:D011241', 'Chemical') :: ['prednisone'] @entity10622 :: ('7248', 'Gene') :: ['TSC1'] @entity2239 :: ('MESH:C107135', 'Chemical') :: ['everolimus'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity177 :: ('MESH:D051437', 'Disease') :: ['renal and liver function'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity19213 :: ('2475', 'Gene') :: ['MTOR'] @entity1205 :: ('MESH:C067311', 'Chemical') :: ['docetaxel']
@entity229 :: (MESH:D011241,Chemical) :: ['prednisone']
