| General information |
| Database: | DB00981 |
| Objective: | Poly adenosine diphosphate (ADP)ribose polymerase (PARP) is essential in cellular processing of DNA damage via the base excision repair pathway (BER). The PARP inhibition can be directly cytotoxic to tumour cells and augments the antitumour effects of DNAdamaging agents. This study evaluated the optimally tolerated dose of olaparib (4(34fluorophenyl) methyl1(2H)one; AZD2281, KU0059436), a potent PARP inhibitor, with dacarbazine and assessed safety, toxicity, clinical pharmacokinetics and efficacy of combination treatment |
| Authors: | Khan OA, et al |
| Title: | a phase I study of the safety and tolerability of olaparib (AZD2281, KU0059436) and dacarbazine in patients with advanced solid tumours. |
| Journal: | Br J Cancer. |
| Year: | 2011 |
| PMID: | 21326243 |
| Trial Design |
| Clinical Trial Id: | NCT00516802 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | olaparib (AZD2281, KU0059436) + dacarbazine |
| Study Type: | a phase I study |
| Key Patients Feature: | Patients with advanced cancer |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients with advanced cancer received olaparib (20200 mg PO) on days 17 with dacarbazine (600800 mg m(2) IV) on day 1 (cycle 2, day 2) of a 21day cycle. An expansion cohort of chemonaive melanoma patients was treated at an optimally tolerated dose. |
| Primary End Point: | safety, toxicity, clinical pharmacokinetics and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 40 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | 82 days (95% confidence interval (CI): 38-108 days) in the doseescalationphase in refractory solid tumour patients and 42 days (95% CI: 36-84 days) for chemotherapynaive melanoma patients. The median time to disease progression overall was 43 days (95% CI: 36-108 days). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most frequent toxicities were neutropaenia and anaemia, although nausea, fatigue, anorexia, diarrhoea and thrombocytopaenia were common. |
| Conclusions: | This study defined a tolerable dose of olaparib in combination with dacarbazine, but there they were no responses in chemonaive melanoma patients, demonstrating no clinical advantage over singleagent dacarbazine at these doses. |