| General information |
| Database: | DB00997 |
| Objective: | Cisplatin and gemcitabine is the standard firstline chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. they aimed to assess the effect of the addition of cediranib (an oral inhibitor of VEGF receptor 1, 2, and 3) to cisplatin and gemcitabine on progression free survival |
| Authors: | Valle JW, et al |
| Title: | Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC03): a randomisedphase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 26179201 |
| Trial Design |
| Clinical Trial Id: | NCT00939848 |
| Agent: | cediranib
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | biliary tract and gallbladder cancer |
| Cancer Subtype: | advanced biliary tract cancer (ABC03) |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Cediranib + cisplatin + gemcitabine chemotherapy |
| Study Type: | multicentre, placebocontrolled, randomisedphase II study |
| Key Patients Feature: | patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK. patients were eligible if they had an ECOG performance status of 01 and an estimated life expectancy of longer than 3 months. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo in combination with cisplatin and gemcitabine chemotherapy versus Cediranib in combination with cisplatin and gemcitabine chemotherapy |
| Treatment Info: | patients were given firstline cisplatin and gemcitabine chemotherapy (25 mg/m(2) cisplatin and 1000 mg/m(2) gemcitabine [on days 1 and 8 every 21 days, for up to eight cycles]) with either 20 mg oral cediranib or placebo once a day until disease progression. |
| Primary End Point: | progression free survival in the intentiontotreat population. |
| Secondary End Point: | NA |
| Patients Number: | 124 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 78% patients in the cediranib group and 65% in the placebo group. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.0 months (95% CI 6.59.3) in the cediranib group and 7.4 months (5.78.5) in the placebo group (HR 0.93, 80% CI 0.741.19, 95% CI 0.651.35; p=0.72). |
| Median OS A vs. C: | 14.1 months (95% CI 10.2-16.4) in patients given cediranib and 11.9 months (9.2-14.3) in patients given placebo (HR 0.86, 95% CI 0.58-1.27; p=0.44). |
| Adverse Event(agent arm): | they noted no significant difference between treatment groups with respect to grade 3-4 haematological toxic effects, although patients receiving cediranib had more frequent grade 3-4 decreased platelet counts |
| Conclusions: | Cediranib did not improve the progression free survival of patients with advanced biliary tract cancer in combination with cisplatin and gemcitabine, which remains the standard of care. Although patients in the cediranib group had more adverse events, they recorded no unexpected toxic effects. The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational. |