| General information |
| Database: | DB00239 |
| Objective: | Androgen receptormediated transcription is directly coupled with the induction of DNA damage, and castrationresistant tumor cells exhibit increased activity of poly (ADPribose) polymerase (PARP)1, a DNA repair enzyme. This study assessed the efficacy and safety of low dose oral PARP inhibitor veliparib (ABT888) and temozolomide (TMZ) in docetaxelpretreated patients with metastatic castrationresistant prostate cancer (mCRPC) in a singlearm, openlabel, pilot study. |
| Authors: | Hussain M, et al |
| Title: | Targeting DNA repair with combination veliparib (ABT888) and temozolomide in patients with metastatic castrationresistant prostate cancer. |
| Journal: | Invest New Drugs. |
| Year: | 2014 |
| PMID: | 24764124 |
| Trial Design |
| Clinical Trial Id: | NCT00526617 |
| Agent: | veliparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | veliparib (ABT888)+temozolomide (TMZ) |
| Study Type: | a singlearm, openlabel, pilot study |
| Key Patients Feature: | Patients with mCRPC progressing on at least one docetaxelbased therapy and prostate specific antigen (PSA) more than and equal to 2 ng/mL. Median baseline PSA was 170 ng/mL. |
| Biomarker: | PSA |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with veliparib 40 mg twice daily on days 17 and TMZ once daily (150 mg/m(2)/day cycle 1; if well tolerated then 200 mg/m(2)/day cycle 2 onwards) on days 15 q28 days. Patients received 2 (median) treatment cycles (range, 19). |
| Primary End Point: | confirmed PSA response rate (decline more than and equal to 30 %). |
| Secondary End Point: | NA |
| Patients Number: | 26 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Two patients had a confirmed PSA response (8.0 %; 95 % CI: 1.026.0), 13 stable PSA, and 10 PSA progression. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 9 weeks (95 % CI: 7.917) |
| Median OS A vs. C: | 39.6 weeks (95 % CI: 26.6not estimable). |
| Adverse Event(agent arm): | The most frequent treatmentemergent adverse events (AEs) were thrombocytopenia (77 %), anemia (69 %), fatigue (50 %), neutropenia (42 %), nausea (38 %), and constipation (23 %). Grade 3/4 AEs occurring in > 10 % of patients were thrombocytopenia (23 %) and anemia (15 %). |
| Conclusions: | Veliparib and TMZ combination was well tolerated but with modest activity. Biomarker analysis supported the proof of concept that this combination has some antitumor activity in mCRPC. |