ABC-04 a Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
This trial is active, not recruiting.
|Conditions||biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms|
|Treatments||selumetinib, gemcitabine, cisplatin|
|Phase||phase 1/phase 2|
|Sponsor||University College, London|
|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.
|Endpoint classification||safety study|
|Intervention model||single group assignment|
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
time frame: From baseline to end of treatment
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).
|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.|
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