| General information |
| Database: | DB00515 |
| Objective: | This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221). |
| Authors: | Del Conte G, et al |
| Title: | Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. |
| Journal: | Br J Cancer. |
| Year: | 2014 |
| PMID: | 25025963 |
| Trial Design |
| Clinical Trial Id: | NCT00819221 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumours |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | olaparib + liposomal doxorubicin |
| Study Type: | Phase I, openlabel, multicentre dosefindingstudy |
| Key Patients Feature: | Eligible patients were aged X18 years with histologically/cytologically confirmed metastatic cancer; adequate bonemarrow, hepatic and renal functions; ECOG performance statusp2; and p3 before chemotherapy regimens for advanced disease.gBRCA mutation status was obtained retrospectively for patients inwhom gBRCA testing had been performed before study entry.Exclusion criteria included active treatment or highdose radiotherapy within the last 28 days, prior cumulative dosing(4300 mg m 2) of doxorubicin equivalent, anthracycline resistance and persistent Common Terminology Criteria (CTC) gradeX2 toxicities caused by prior therapy |
| Biomarker: | germline BRCA1/2 (gBRCA)mutated |
| Biomark Analysis: | A total of 13 responders had ovarian cancer: 10 were platinumsensitive, 11 had a gBRCA mutation. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received 28day cycles of olaparib, continuously (days 128) or intermittently (days 17), plus PLD (40 mg m(2), day 1); seven olaparib dose cohorts (50400 mg bid) were explored to determine the recommended dose. |
| Primary End Point: | safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)). |
| Secondary End Point: | NA |
| Patients Number: | 44 |
| Trial Results |
| DLT_MTD: | The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. |
| Objective Response Rate: | The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinumsensitive, 11 had a gBRCA mutation. |
| 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): | Grade X3 and serious Aes were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. |
| Conclusions: | Continuousintermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m(2)) was generally tolerated and showed evidence of antitumour activity in ovarian cancer. |