| General information |
| Database: | DB01087 |
| Objective: | AT101 binds and inhibits the antiapoptotic function of Bcl2, BclxL, Mcl1, and Bclw and is a potent stimulator of proapoptotic proteins. In this multiinstitutionphase I/II trial, they evaluated the safety and efficacy of singleagent AT101, in men with chemotherapy na ve, castrateresistant prostate cancer (CRPC). |
| Authors: | Liu G, et al |
| Title: | An openlabel, multicenter, phase I/II study of singleagent AT101 in men with castrateresistant prostate cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2009 |
| PMID: | 19366825 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | AT101
|
| Target: | Bcl2, BclxL, Mcl1, and Bclw
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | castrateresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multiinstitutionphase I/II trial |
| Key Patients Feature: | men with chemotherapy na ve, castrateresistant prostate cancer (CRPC). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts were to be treated with escalating doses of AT101 on a continuous daily basis until the maximally tolerated dose was achieved. At the recommendedphase 2 dose, an additional 21 patients were planned to assess for preliminary evidence of efficacy. |
| Primary End Point: | MTD, AEs, OR |
| Secondary End Point: | NA |
| Patients Number: | 23 |
| Trial Results |
| DLT_MTD: | the phase II starting dose was chosen to be 30 mg/day for 21 of 28 days. |
| Objective Response Rate: | Two patients had a confirmed > or =50% posttherapy prostatespecific antigen decline. No objective responses (Response Evaluation Criteria in Solid Tumors) were observed. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent observed adverse events (any grade) were diarrhea (43.5%), fatigue (34.8%), nausea (21.7%), anorexia (21.7%), and small intestinal obstruction (21.7%). Due to the high incidence of grade 3 small intestinal obstruction (n = 5; 21.7%), a reduction in dose to 20 mg/day for 21 of 28 days was mandated for all patients. |
| Conclusions: | AT101 administered at 20 mgday for 21 of 28 days was welltolerated. Evidence of singleagent clinical activity was observed with prostatespecific antigen declines in some patients. Further investigation of AT101 in prostate cancer is warranted and trials combining AT101 with androgen deprivation, as well as with docetaxel chemotherapy are ongoing. |