| General information |
| Database: | DB00519 |
| Objective: | Poly(ADPribose) polymerase (PARP)inhibitors and antiangiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. they investigated the toxicities and recommendedphase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)1/2/3 and olaparib, a PARPinhibitor (NCT01116648). |
| Authors: | Liu JF, et al |
| Title: | a phase 1 trial of the poly(ADPribose) polymerase inhibitor olaparib (AZD2281) in combination with the antiangiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triplenegative breast cancer. |
| Journal: | Eur J Cancer. |
| Year: | 2013 |
| PMID: | 23810467 |
| Trial Design |
| Clinical Trial Id: | NCT01116648 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | ovarian cancer and breast cancer |
| Cancer Subtype: | epithelial ovarian or triplenegative breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | olaparib (AZD2281)+ cediranib (AZD2171) |
| Study Type: | an openlabel, phase I, doseescalation trial |
| Key Patients Feature: | age more than and equal to 18 years, ECOG performance status 0 or 1, life expectancy>6 months, and either recurrent epithelial ovarian, fallopian tube, or primary peritonealcancer, or metastatic TNBC. Ovarian cancer patients were required to have measurabledisease by RECIST 1.1 or an elevated CA125 level more than and equal to twice the upper limit of normal on twooccasions at least 1 day but not more than 3 months apart; they also needed to have receiveda firstline platinumbased regimen. Breast cancer patients needed to have measurabledisease by RECIST 1.1 and had to have recurred after both an adriamycin and taxanecontaining regimen. Prior PARPinhibitors or antiangiogenics were allowed in the adjuvantbut not recurrent or metastatic settings. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were assigned to a treatment cohort and 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 dose limiting toxicities (DLT) and maximum tolerated dose (MTD). |
| Secondary End Point: | treatmentrelated toxicities and preliminary assessment of clinical activity |
| Patients Number: | 28 |
| Trial Results |
| DLT_MTD: | 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia more than and equal to 4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. |
| Objective Response Rate: | The overall response rate (ORR) in the 18 RECISTevaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD) > 24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for > 24 weeks. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS was 8.7 months for ovarian cancer patients and 3.7 months for breast cancer patients. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 botheyl obstruction occurred. |
| Conclusions: | The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. |