ABC-04 a Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
The objective of this study is to establish the recommended dose of selumetinib, a novel MEK inhibitor for use in combination with gemcitabine and cisplatin.
Biliary Tract Neoplasms
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||ABC-04 a Phase 1B Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer|
- To investigate the safety and tolerability of the combination of cisplatin, gemcitabine and selumetinib, and to establish the recommended phase II dose of selumetinib when given in this combination. [ Time Frame: from baseline to 28 days post last patient last treatment ] [ Designated as safety issue: Yes ]
To investigate the safety and tolerability of the combination of cisplatin, gemcitabine (CisGem) and selumetinib and to establish the recommended phase II dose of selumetinib when given in this combination.
The recommended dose of selumetinib to use in combination with CisGem in future studies will be the dose at which less than 33% of patients experience a DLT. The recommended dose will not be higher than 75mg/m*2
- Response rate [ Time Frame: From baseline to end of treatment ] [ Designated as safety issue: No ]To make a preliminary assessment of efficacy in terms of tumour control.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||January 2015|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Experimental: single armed
This is not a randomised trial, there is only one study group. All patients will receive cisplatin/gemcitabine chemotherapy in addition to oral daily dosing of selumetinib
The starting dose of selumetinib will depend on the cohort. The first dose of selumetinib to be studied will be 75 mg twice daily (bd). Selumetinib will be taken every day (continuously) either once or twice a day, depending on the dose. Treatment with selumetinib may continue until disease progression.
Other Name: AZD6244Drug: gemcitabine
gemcitabine: taken in combination with cisplatin will be given at 1000 mg/m*2 in 250 - 500 ml 0.9% saline over 30 minutes by intravenous infusion on days 1, and 8 of each 21-day cycle for eight cycles in totalDrug: cisplatin
cisplatin: 25 mg/m*2 in 1000 ml 0.9% saline given over 1 hour followed by 500mls 0.9% saline over 30 minutes followed by gemcitabine on days 1, and 8 of each 21-day cycle for eight cycles in total
This trial aims to evaluate the safety and tolerability of selumetinib in combination with CisGem and to establish the recommended dose to take into phase II studies. Pharmacokinetic and pharmacodynamic endpoints will be assessed and preliminary efficacy data will also be collected.
Patients with Advanced Biliary tract Cancer will receive CisGem regimen and selumetinib. A dose de-escalation scheme will be employed to determine the recommended phase II dose of selumetinib.
Patients will be recruited in cohorts of three and assessed for dose limiting toxicity (DLT) during the first cycle of treatment. Depending on the number of DLTs observed, the cohort may be expanded, the next cohort may be enrolled at a lower dose or the dose may be declared the recommended dose. Patients will receive up to eight cycles of CisGem and may continue to receive selumetinib until progression of disease.