Clinical trial NCT02151084: A Study of Different Dosing Schedules of Selumetinib With Cisplatin/Gemcitabine (CIS/GEM) Versus CIS/GEM Alone in Biliary Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Biliary Tract Carcinoma
Gallbladder Carcinoma
Keywords: randomized
selumetinib
tablets
cisplatin
gemcitabine
non-resectable
recurrent
metstatic
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2014-05-30
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in tumor size in millimetres
timeFrame: 10 weeks post initiation of therapy
Secondary outcomes:
measure: Number of participants with objective response and/or stable disease
timeFrame: 6 months post initiation of therapy
measure: Percentage of patients without progressive disease
timeFrame: 10 weeks post initiation of therapy
measure: Progression-free survival in months
timeFrame: Enrollment to disease progression or death
measure: Overall survival in months
timeFrame: Time from enrollment to date of death
measure: Total incidence of adverse events
timeFrame: 2 years
measure: Total rate of grade 3 and 4 toxicities
timeFrame: 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Jennifer Knox, M.D.
role: PRINCIPAL_INVESTIGATOR
References: