NCT00939848

Cediranib Versus Placebo Plus Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers

Randomised Phase II Trial of Cediranib (AZD2171) Versus Placebo in Addition to Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 124 (actual)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

As a result of our previous NCRN study (ABC-02) cisplatin and gemcitabine (CisGem) is likely to become the international standard of care for patients with advanced biliary tract cancer (submitted: ASCO 2009). This study, ABC-03, will determine whether the addition of cediranib(an oral Vascular Endothelial Growth Factor Receptor inhibitor) to CisGem will improve the time to disease progression in this patient group.

Detailed description

Although there is currently no standard chemotherapy for patients with advanced biliary tract cancers (ABC) the UK ABC-02 study (the largest study by far in this patient group, n=410) is likely to define CisGem as the global standard of care for this disease based on a significantly improved progression-free survival and overall survival compared to gemcitabine alone. Vascular endothelial growth factor (VEGF) is a pivotal stimulus of physiologic and pathologic angiogenesis, including the sustained neo-vascularisation required to support solid tumour growth. Human biliary tract carcinoma cells have higher expression of VEGF both in cell lines and tissues (detected in 75.6% of 33 resected clinical specimens) and this is associated with significantly higher levels of microvessel density and the presence of intrahepatic metastases. Cediranib is a highly potent inhibitor of VEGF receptor 2 tyrosine kinase and VEGF-induced signalling in endothelial cells. It has been safely combined with a CisGem regimen in lung cancer patients. Aims This trial aims to evaluate the effect on progression-free survival of cediranib in combination with CisGem chemotherapy compared to CisGem and placebo. Summary of study Consenting patients with ABC (inoperable, locally advanced, recurrent or metastatic) will receive CisGem chemotherapy and either cediranib (experimental arm) or placebo (standard arm) orally. Treatment will continue until disease progression (chemotherapy will stop at 24 weeks) with tumour reassessment by CT/MRI scans at 12-weekly intervals. All patients will be followed up for survival analysis.

Conditions

• Biliary Tract Neoplasms

Interventions

Type	Name	Description
DRUG	gemcitabine	gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
DRUG	cisplatin	cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
DRUG	Placebo	20mg od (continuous dosing) until evidence of disease progression has been confirmed
DRUG	cisplatin	cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
DRUG	cediranib	cediranib 20mg oral daily (continuous dosing)until evidence of disease progression has been confirmed
DRUG	gemcitabine	gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression

Timeline

• Start date: 2011-04-01
• Primary completion: 2012-09-01
• Completion: 2014-09-01
• First posted: 2009-07-15
• Last updated: 2014-10-27

Locations

2 sites across 1 country: United Kingdom