| General information |
| Database: | DB00229 |
| Objective: | AT101 (A), a small molecule oral inhibitor of the Bcl2 family, has activity alone and in combination with docetaxel (Taxotere) and prednisone (DP) in metastatic castrationresistant prostate cancer (mCRPC). A randomized, doubleblind, placebocontrolledphase II trial compared DP combined with either AT101 (A) or placebo in chemonaive mCRPC. |
| Authors: | Sonpavde G, et al |
| Title: | Randomizedphase II trial of docetaxel plus prednisone in combination with placebo or AT101, an oral small molecule Bcl2 family antagonist, as firstline therapy for metastatic castrationresistant prostate cancer. |
| Journal: | Ann Oncol |
| Year: | 2012 |
| PMID: | 22112969 |
| Trial Design |
| Clinical Trial Id: | NCT00286793 |
| Agent: | AT101
|
| Target: | Bcl2, BclxL, Mcl1, and Bclw
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | docetaxel+prednisone +AT101 |
| Study Type: | A randomized, doubleblind, placebocontrolledphase II trial |
| Key Patients Feature: | Men with progressive mCRPC despite androgen deprivation were eligible |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | docetaxel plus prednisone + placebo |
| Treatment Info: | patients were randomized 1:1. Patients received docetaxel (75 mg/m2 day 1) and prednisone 5 mg orally twice daily every 21 days with either AT101 (40 mg) or placebo twice daily orally on days 13. |
| Primary End Point: | overall survival (OS). |
| Secondary End Point: | NA |
| Patients Number: | 221 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS was also similar in both arms (11.0 versus 10.3 months, HR 0.88, 95% CI 0.63-1.22, P = 0.53) |
| Median OS A vs. C: | Median OS for AT101 plus docetaxelprednisone (ADP) and placeboDP was 18.1 versus 17.8 months [hazard ratio (HR) 1.07, 95% confidence interval 0.721.55, P=0.63].In a subgroup of highrisk mCRPC (n=34), outcomes appeared to favor ADP (median OS 19 versus 14 months). |
| Adverse Event(agent arm): | Grade 3/4 toxic effects for ADP versus placeboDP were cardiac events (5% versus 2%), lymphopenia (23% versus 16%), neutropenia (47% versus 40%), ileus (2% versus 0%) and pulmonary embolism (6% versus 2%). |
| Conclusions: | AT101 was tolerable but did not extend OS when combined with DP in mCRPC; a potential benefit was observed in highrisk patients. |