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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gemcitabine, capecitabine and ZD6474 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gemcitabine | Drug | Gemcitabine administered intravenously over 30 minutes on days 1, 8 and 15 of each cycle at a fixed dose of 1000mg/m2. |
|
| 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 |
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Inclusion Criteria:
Blood samples and other testing may apply for further testing of eligibility.
Exclusion Criteria:
Further exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Stephen Leong, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Denver | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26715573 | Derived | Kessler ER, Eckhardt SG, Pitts TM, Bradshaw-Pierce EL, O'byrant CL, Messersmith WA, Nallapreddy S, Weekes C, Spratlin J, Lieu CH, Kane MA, Eppers S, Freas E, Leong S. Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers. Invest New Drugs. 2016 Apr;34(2):176-83. doi: 10.1007/s10637-015-0316-5. Epub 2015 Dec 30. |
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| ID | Term |
|---|---|
| D001661 | Biliary Tract Neoplasms |
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001660 | Biliary Tract Diseases |
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| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| D000069287 | Capecitabine |
| C452423 | vandetanib |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| Capecitabine | Drug | Capecitabine administered orally at 1660 mg/m2/day divided into two doses for 21 days followed by a week-off. |
|
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| ZD6474 | Drug | Administered orally at 300 mg/day once daily. One cycle will consist of 28 days |
|
|
| D004066 |
| Digestive System Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |