Vandetanib Gemcitabine Or Placebo Plus Gemcitabine Or Vandetanib Monotherapy In Advanced Biliary Tract Cancer

Study Overview
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Brief Summary
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The primary objective of the trial is to determine the efficacy of VANDETANIB monotherapy or VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE in prolonging the progression-free survival (PFS) at the trial closure in patients with advanced (unresectable or metastatic) biliary tract cancer.

Official Title
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A Randomized, Multicentre, Phase II, Parallel-Group Trial of Vandetanib Monotherapy or Vandetanib in Combination With Gemcitabine Versus Gemcitabine Plus Vandetanib Matching Placebo in Subjects With Advanced Biliary Tract Cancer (Gallbladder Cancer, Cancer of the Extrahepatic Bile Duct, Intrahepatic Cholangiocarcinoma and Ampullary Carcinoma)

Conditions
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Biliary Tract Cancer, Gallbladder Cancer, Cancer Of The Extrahepatic Bile Duct, Ampullary Carcinoma

Intervention / Treatment
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* Drug: ZD6474, Vandetanib
* Drug: ZD6474, Vandetanib
* Drug: Gemcitabine
* Drug: Placebo matching ZD6474


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically-confirmed advanced (unresectable or metastatic) biliary tract cancer (gallbladder cancer, cancer of the extrahepatic bile duct, intrahepatic cholangiocarcinoma and ampullary carcinoma) Patients must have measurable or evaluable but non-measurable disease Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted). WHO performance status 0 to 2: patients must have a WHO PS ≤ 2 Exclusion Criteria: Patients must not have received prior systemic therapy for advanced (unresectable or metastatic) disease; prior chemotherapy in the adjuvant setting within 3 months before the trial entry is accepted Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance wit Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Vandetanib 300 mg as a once daily oral dose, from Day 1 | Drug: ZD6474, Vandetanib<br>* 300 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>* Other names: Zactima;|
| Experimental: B<br>Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy) | Drug: ZD6474, Vandetanib<br>* 100 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>* Other names: Zactima;Drug: Gemcitabine<br>* administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles or until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>* Other names: Gemzar;|
| Placebo Comparator: C<br>Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy). | Drug: Gemcitabine<br>* administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles or until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>* Other names: Gemzar;Drug: Placebo matching ZD6474<br>* Placebo to match ZD6474 100 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression was defined as Time from the date of first dose of study medication to progression of disease, or death (it also includes patients who are lost to follow-up or have withdrawn consent) and evaluated with RECIST criteria as an increase of at least 20% in the sum of longest diameter (LD) of target lesion(s) taking as reference the smallest sum of LD since the treatment started or any new lesion(s). | up to 1032 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Rate (CR+PR), | Objective Tumor Response Rate was defined as complete response (CR) + partial response (PR) evaluated by RECIST. CR was defined as disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of longest diameters (LD) of target lesion(s) taking as reference the baseline sum of LD | up to 1032 days | 
| Disease Control Rate (CR+PR+SD) | DCR is the sum of patients with a best overall CR, PR or SD (>=8 weeks) by the patient in the analysis | up to 1032 days | 
| Duration of Response (DOR) | DOR is defined from the date of first documentation of response until date of PD or death | up to 1032 days | 
| Overall Survival | OS is defined from the date of randomization to death | up to 1032 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intrahepatic, Cholangiocarcinoma, Vandetanib, Zactima, Advanced, Biliary, Tract, Gallbladder, Extrahepatic Bile Duct, Intrahepatic Cholangiocarcinoma, Ampullary Carcinoma