This trial is active, not recruiting.

Conditions biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms
Treatments selumetinib, gemcitabine, cisplatin
Phase phase 1/phase 2
Target MEK
Sponsor University College, London
Collaborator AstraZeneca
Start date February 2012
End date March 2013
Trial size 30 participants
Trial identifier NCT01242605, 2010-018522-39, ABC-04


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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
selumetinib AZD6244
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.
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 total
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

Primary Outcomes

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

Secondary Outcomes

Response rate
time frame: From baseline to end of treatment

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - A histopathological or cytological diagnosis of non-resectable, recurrent or metastatic biliary tract (intra- or extra-hepatic), gallbladder or ampullary carcinoma - ECOG performance status 0, 1, or 2 - Age ≥ 18 - Estimated life expectancy > 3 months - Adequate haematological function: - Haemoglobin * 10g/dL (prior transfusions for patients with low haemoglobin are allowed) - WBC >/= 3.0 x 10*9/L - Absolute neutrophil count (ANC) >/= 1.5 x 10*9/L - Platelet count >/= 100,000/mm*3) - Adequate liver function: - Total bilirubin ≤1.5 x upper limit of normal (ULN) OR ≤ 3.0 x upper limit of normal (ULN) if stable for a duration of two weeks • ALT and/or AST & alkaline phosphatase ≤ 5 x ULN - Adequate renal function: - Serum urea and serum creatinine < 1.5 times ULN - Calculated GFR >/= 45 mL/min. If the calculated GFR is below 60, isotope EDTA confirmation of adequate renal function is required - No evidence of active uncontrolled infection (patients on antibiotics are eligible) - Capable of giving written informed consent Exclusion Criteria: - Incomplete recovery from previous surgery. - Patients undergoing current treatment with curative intent. - History of prior malignancy that could interfere with the response evaluation (exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, any early stage (stage I) malignancy adequately resected for cure greater than 5 years previously). - Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial. - Any psychiatric or other disorder (eg brain metastases) likely to impact on informed consent. - Pregnancy or breast-feeding. •Women of child-bearing potential should must have a negative pregnancy test prior to study entry AND be using an adequate contraception method, which must be continued for 3 months after completion of chemotherapy - NB. Whilst not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, baseline audiograms are recommended and, in those randomised to cisplatin, should be followed by repeat audiograms prior to cycle 2. - Patients with any grade NYHA cardiomyopathy and uncontrolled hypertension (>150/95mmhg).

Additional Information

Official title ABC-04 a Phase 1B Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
Principal investigator John Bridgewater, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2013.
Information provided to ClinicalTrials.gov by University College, London.