Gemcitabine/Capecitabine/ZD6474 in Advanced Solid Tumors

Study Overview
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Brief Summary
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Zactima will be used in this study to determine the highest dose that can be given safely as well as the side effects of Zactima when in combination with two FDA approved drugs; gemcitabine and capecitabine. This combination will be given to patients with advanced solid tumors. Once the highest dose of the combination has been determined, additional patients with biliary cancers (cholangiocarcinomas and gallbladder cancer) and locally advanced or metastatic pancreatic cancer will be treated at the highest determined dose for further studies.

Detailed Description
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This phase I study will access a novel regimen using a multi-targeted anti-angiogenic agent which targets the tyrosine kinase of vascular endothelial growth factor (VEGF) receptor 2 and epidermal growth factor receptor (EGFR) in combination with cytotoxic agents: gemcitabine and capecitabine. The rationale is based on observations that there is an additive / synergistic effect when cytotoxic agents are combined with angiogenesis inhibitors. There is also evidence that EGFR mediated signaling pathways are potent stimulators of VEGF production. Also the concept of dual targeting of tumor and endothelial cells may provide more encouraging results.

Official Title
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A Phase I Study of Gemcitabine, Capecitabine and ZD6474 (ZACTIMA) in Patients With Advanced Solid Tumors With an Expanded Cohort of Patients With Biliary or Pancreatic Malignancies.

Conditions
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Malignant Solid Tumour, Biliary Cancer, Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Capecitabine
* Drug: ZD6474


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (measure of your ability to perform everyday tasks) Life expectancy of at least three months Blood samples and other testing may apply for further testing of eligibility. Exclusion Criteria: Uncontrolled illness (for example, current infections or heart conditions) Abnormal laboratory tests (such as blood or urine testing) Pregnant or breastfeeding women Further exclusion criteria may apply.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemcitabine, capecitabine and ZD6474<br>Gemcitabine administered intravenously over 30 minutes on days 1, 8 and 15 of each cycle at a fixed dose of 1000mg/m2. Capecitabine administered orally at 1660 mg/m2/day divided into two doses for 21 days followed by a week-off . ZD6474 administered orally at 300 mg/day once daily. One cycle will consist of 28 days. | Drug: Gemcitabine<br>* Gemcitabine administered intravenously over 30 minutes on days 1, 8 and 15 of each cycle at a fixed dose of 1000mg/m2.<br>* Other names: Gemzar;Drug: Capecitabine<br>* Capecitabine administered orally at 1660 mg/m2/day divided into two doses for 21 days followed by a week-off.<br>* Other names: Xeloda;Drug: ZD6474<br>* Administered orally at 300 mg/day once daily. One cycle will consist of 28 days<br>* Other names: Zactima;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of ZACTIMA (ZD6474) in combination with Gemcitabine and Capecitabine | To evaluate the safety profile and determine the MTD dose of ZACTIMA in combination with Gemcitabine and Capecitabine in patients with advanced malignancies. Toxicity will be graded per Common Toxicity Criteria for Adverse Effects (CTCAE) Version 3.0 and adverse event reporting for this study will be performed via Adverse Event Expedited Reporting System (AdEERS). All patients who receive any amount of the study drug will be evaluable for toxicity. | Up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumors, Biliary or Pancreatic Malignancies