| General information |
| Database: | DB00518 |
| Objective: | To establish the maximum tolerated dose, determine safety/tolerability and evaluate the pharmacokinetics and preliminary efficacy of olaparib in combination with cisplatin in patients with advanced solid tumors. |
| Authors: | Balma a J, et al |
| Title: | Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 24827126 |
| Trial Design |
| Clinical Trial Id: | NCT00782574 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | breast cancer, ovarian cancer |
| Cancer Subtype: | advanced breast, ovarian and other solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | olaparib + cisplatin |
| Study Type: | phase I, openlabel, multicenter study |
| Key Patients Feature: | Eligible patients were aged more than and equal to 18 years and had histologically confirmed metastatic cancer that was not amenable to surgery or radiation therapy;progressed on standard therapy; an Eastern Cooperative Oncology Group(ECOG) performance status less than and equal to 2; life expectancy of more than and equal to 12 weeks; and adequatehematologic, hepatic and renal function. |
| Biomarker: | BRCA1/2 mutation |
| Biomark Analysis: | The overall objective response rate was 41% for patients with measurable disease, and 43% and 71% among patients with a BRCA1/2 mutation who had ovarian and breast cancer, respectively. |
| Control Group Info: | single arm |
| Treatment Info: | pts received oral olaparib [50200 mg twice daily (bid); 21day cycle] continuously or intermittently (days 15 or 110) in combination with cisplatin (6075 mg/m(2) intravenously) on day 1 of each cycle. |
| Primary End Point: | the safety and tolerability and to define the MTD for this treatment combination. |
| Secondary End Point: | compare the exposure of olaparib alone and in combination with cisplatin, and to assess the antitumor activity of olaparib in combination with cisplatin by objective response rate (ORR). |
| Patients Number: | 59 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicities (DLTs) of grade 3 neutropenia (cisplatin 75 mg/m2 with continuous olaparib 100 mg bid or 200 mg bid; n = 1 each) and grade 3 lipase elevation (cisplatin 75 mg/m2 with olaparib 100 mg bid days 1-10 or 50 mg bid days 1-5; n = 1 each) were reported. |
| Objective Response Rate: | The ORR for all patients with measurable disease at baseline was 41% (19/46 patients)The median (range) time to onset of response was 48 (35-172) days; of the patients who experienced an objective response and received olaparib monotherapy, all 15 achieved the response before starting monotherapy. |
| 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 grade more than and equal to 3 adverse events were neutropenia (16.7%), anemia (9.3%) and leucopenia (9.3%). Thirty patients (55.6%) received colonystimulating factors for hematologic support. |
| Conclusions: | Olaparib in combination with cisplatin 75 mg/m(2) was not considered tolerable; intermittent olaparib (50 mg bid, days 15) with cisplatin 60 mg/m(2) improved tolerability. Promising antitumor activity in patients with germline BRCA12 mutations was observed and warrants further investigation. |