| General information |
| Database: | DB00158 |
| Objective: | a firstinhuman study of the poly (ADPribose) polymerase (PARP) inhibitor ABT888 in patients with advanced malignancies. |
| Authors: | Kummar S, et al |
| Title: | Phase 0 clinical trial of the poly (ADPribose) polymerase inhibitor ABT888 in patients with advanced malignancies. |
| Journal: | J Clin Oncol |
| Year: | 2009 |
| PMID: | 19364967 |
| Trial Design |
| Clinical Trial Id: | NCT00387608 |
| Agent: | veliparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase 0 Clinical Trial |
| Key Patients Feature: | patients with advanced malignancies |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | ABT888 was administered as a single oral dose of 10, 25, or 50 mg to determine the dose range and time course over which ABT888 inhibits PARP activity in tumor samples and peripheral blood mononuclear cells, and to evaluate ABT888 pharmacokinetics. Blood samples and tumor biopsies were obtained pre and postdrug administration for evaluation of PARP activity and pharmacokinetics. |
| Primary End Point: | a dose range and time course over which ABT888 inhibited PARP activity, as well as the PK of ABT888;PD modulation |
| Secondary End Point: | NA |
| Patients Number: | 13 |
| Trial Results |
| DLT_MTD: | ABT888 demonstrated good oral bioavailability and was well tolerated. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Statistically significant inhibition of poly (ADPribose) levels was observed in tumor biopsies and peripheral blood mononuclear cells at the 25mg and 50mg dose levels. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | Within 5 months of study activation, they obtained pivotal biochemical and pharmacokinetic data that have guided the design of subsequentphase I trials of ABT888 in combination with DNAdamaging agents. In addition to accelerating the development of ABT888, the rapid conclusion of this trial demonstrates the feasibility of conducting proofofprinciplephase 0 trials as part of an alternative paradigm for early drug development in oncology. |