Cediranib Versus Placebo Plus Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers (ABC-03)
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.
Biliary Tract Neoplasms
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Randomised Phase II Trial of Cediranib (AZD2171) Versus Placebo in Addition to Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers|
- Progression free survival [ Time Frame: six months ] [ Designated as safety issue: No ]
- • Response Rate (RECIST) • Toxicity • Survival (as part of the follow-on phase III study) • Biomarker evaluation (inc. circulating VEGF, sVEGFR-2, bFGF, LDH and CA 19-9) • Quality of Life [ Time Frame: 3 years minimum ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||September 2014|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
The experimental arm will consist of cisplatin 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle with cediranib 20mg oral daily (continuous dosing).
cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progressionDrug: cediranib
cediranib 20mg oral daily (continuous dosing)until evidence of disease progression has been confirmed
Other Name: AZD2171Drug: gemcitabine
gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
Placebo Comparator: Arm A
The control arm will consist of cisplatin 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle with a matching placebo 20mg oral daily (continuous dosing)
gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progressionDrug: cisplatin
cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progressionDrug: Placebo
20mg od (continuous dosing) until evidence of disease progression has been confirmed
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.
|University College London Hospitals NHS Foundation Trust|
|London, United Kingdom, NW1 2PQ|
|The Christie NHS Foundation Trust|
|Manchester, United Kingdom, M20 4BX|
|Principal Investigator:||Juan Valle, MD||Christie Hospital NHS Foundation Trust|