A Study of Different Dosing Schedules of Selumetinib With Cisplatin/Gemcitabine (CIS/GEM) Versus CIS/GEM Alone in Biliary Cancer

Study Overview
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Brief Summary
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This is a phase II study (the second stage of testing a new drug or new drug combinations) to see how useful two different schedules of study drug selumetinib with cisplatin and gemcitabine are compared to cisplatin and gemticabine alone in patients with biliary cancer. Selumetinib, an oral drug which plays an important role in the regulation of cell growth (MEK 1/2 inhibitor) has been shown to shrink tumours in patients with biliary cancer and other types of human cancers. Selumetinib has also been shown to shrink tumours when given in combination with cisplatin and gemcitabine in research studies done in animals and in some patients with biliary tract cancer. Cisplatin and gemcitabine are intravenous drugs that work by damaging DNA in tumor cells so that they are unable to grow and divide.

Official Title
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A Randomized Phase II Trial of MEK Inhibitor Selumetinib (AZD6244) Combined Continuously or Sequentially With Cisplatin/Gemcitabine (CIS/GEM) Versus CIS/GEM Alone in Patients With Advanced Biliary Cancer

Conditions
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Biliary Tract Carcinoma, Gallbladder Carcinoma

Intervention / Treatment
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* Drug: Selumetinib
* Drug: Cisplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable, recurrent or metastatic, measurable biliary tract cancer or gall bladder cancer No prior systemic therapy Performance status 0, 1, or 2 Age 18 years or older Estimated life expectancy > 3 months Adequate hematological, liver, renal function No evidence of active uncontrolled infection Capable of giving written consent Acceptable recovery of previous side effects Exclusion Criteria: Progressing within 3 or 6 months of receiving certain treatments Prior chemotherapy for non-resectable or metastatic disease or a MEK inhibitor Progressing within 6 months of adjuvant treatment. May not have received prior chemotherapy for non-resectable/metastatic disease. Prior MEK, RAS, or RAF inhibitors or history of hypersensitivity to study drugs. Ampullary carcinoma Incomplete recovery from previous surgery Undergoing treatment with curative intent Prior malignancy that could interfere with the response evaluation Severe or uncontrolled systemic diseases or lab finding that makes it undesirable for patient to participate Any psychiatric or other disorder likely to impact consent Pregnant or breastfeeding Patients with significant cardiac-related issues History of eye-related issues. Systemic disease, active infection, bleeding diatheses or renal transplant, including hep B, hep C or HIV Receiving potent inhibitors or inducers of CYP3A4/5, CYP2C19 and CYP1A2 can continue with caution

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Continuous Dosing)<br>Run-In: Selumetinib, orally, BID for 7 days (Day -7 to Day -1) On treatment: Selumetinib, orally, BID from Day 1-21 of every 28 day cycle. Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle. | Drug: Selumetinib<br> <br> * Other names: AZD6244;Drug: Cisplatin<br> <br> * Other names: Platinol;Drug: Gemcitabine<br> <br> * Other names: Gemzar;|
| Experimental: Arm B (Sequential Dosing)<br>Run-In: Selumetinib, orally, BID for 5 days (Day -7 to Day -3) with 2 days washout On treatment: Selumetinib, orally, BID from Day 1-5 and 8-19 of every 28 day cycle. Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle. | Drug: Selumetinib<br> <br> * Other names: AZD6244;Drug: Cisplatin<br> <br> * Other names: Platinol;Drug: Gemcitabine<br> <br> * Other names: Gemzar;|
| Experimental: Arm C (Standard Care)<br>Cisplatin/gemcitabine, intravenously, on Days 1 and 8 of every 28 day cycle. | Drug: Cisplatin<br> <br> * Other names: Platinol;Drug: Gemcitabine<br> <br> * Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tumor size in millimetres | Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | 10 weeks post initiation of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with objective response and/or stable disease |  | 6 months post initiation of therapy | 
| Percentage of patients without progressive disease |  | 10 weeks post initiation of therapy | 
| Progression-free survival in months |  | Enrollment to disease progression or death | 
| Overall survival in months |  | Time from enrollment to date of death | 
| Total incidence of adverse events |  | 2 years | 
| Total rate of grade 3 and 4 toxicities |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized, selumetinib, tablets, cisplatin, gemcitabine, non-resectable, recurrent, metstatic