| General information |
| Database: | DB00522 |
| Objective: | laparib (AZD2281) is an orally active Poly(ADPribose) polymerase (PARP) inhibitor with favorable antitumor activity in advanced ovarian and breast cancers with BRCA1/2 mutations in theystern (USA and European) studies. Thisphase I dosefinding study evaluated the tolerability, pharmacokinetics, PARP inhibitory activity, and antitumor activity of olaparib in Japanese patients with solid tumors. |
| Authors: | Yamamoto N, et al |
| Title: | a phase I, dosefinding and pharmacokinetic study of olaparib (AZD2281) in Japanese patients with advanced solid tumors. |
| Journal: | Cancer Sci. |
| Year: | 2012 |
| PMID: | 22145984 |
| Trial Design |
| Clinical Trial Id: | NCT00572364 |
| Agent: | olaparib
|
| 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 I, dosefinding and pharmacokinetic study |
| Key Patients Feature: | Eligible patients aged 20-74 years with histologically or cytologically confirmed solid tumors for whom no standard therapy existed or no standard therapies were likely toresult in durable remission were included in the study. Allpatients were also required to have: World Health Organization(WHO) performance status ¡ê2; adequate bone marrow, hepaticand renal functions (absolute neutrophil count 1500 mm3, platelet count 100 000 mm3, hemoglobin 9.0 g dl, serumtotal bilirubin ¡ê1.5 times the normal upper limit, aspartate aminotransferase [AST] ¡ê80 IU l, alanine aminotransferase [ALT]¡ê80 IU l, serum creatinine level ¡ê1.2 mg dl); life expectancy 3 months; and a minimum washout period of 4 weeks afterany previous anticancer therapy. BRCA1 or BRCA2 mutation carrier status was not required for eligibility, and was not evaluated in this study. Exclusion criteria included: serious preexisting medical conditions, such as significant cardiovasculardisease and psychogenic disorders; family history of long QTsyndrome or QTc 450 ms; persistent CTCAE grade 2 toxicities (excluding alopecia) caused by prior medication; symptomatic brain metastases; pregnancy or lactation; and hepatitis B orC or human immunodeficiency virus infections. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Olaparib was administered as a singledose on day 1, follotheyd by twicedaily dosing for 28 days from 48 h after a single dose. Doses were escalated from 100 mg b.i.d. in successive cohorts, up to a maximum of 400 mg b.i.d. |
| Primary End Point: | MDT, DLT and PK, safety, efficacy |
| Secondary End Point: | NA |
| Patients Number: | 12 |
| Trial Results |
| DLT_MTD: | doselimiting toxicities were not observed up to and including the 400mg b.i.d. dose level. |
| Objective Response Rate: | NA |
| 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 common adverse events were nausea, increased blood creatinine, decreased hematocrit, leukopenia and lymphopenia; doselimiting toxicities were not observed up to and including the 400mg b.i.d. dose level. |
| Conclusions: | Olaparib was well tolerated up to the 400mg b.i.d. dose in Japanese patients with solid tumors. Preliminary evidence of antitumor activity was observed |