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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-02034 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
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This phase I trial is studying the side effects and best dose of dovitinib lactate when given together with gemcitabine hydrochloride and capecitabine in treating patients with advanced or metastatic solid tumors or advanced pancreatic cancer. Dovitinib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving dovitinib lactate together with combination chemotherapy may kill more tumor cells
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose and recommended phase II dose of dovitinib (dovitinib lactate) when administered concurrently with gemcitabine (gemcitabine hydrochloride) and capecitabine in patients with advanced solid malignancies.
II. To characterize the safety profile of dovitinib, gemcitabine and capecitabine combination in patients with advanced solid malignancies.
SECONDARY OBJECTIVES:
I. To characterize the pharmacokinetic profile of dovitinib, capecitabine, gemcitabine and their metabolites when administered concurrently in patients with advanced solid malignancies.
II. To determine the preliminary efficacy of the study combination in patients with advanced adenocarcinoma of the pancreas or biliary tract.
III. To explore serum and tumor biomarkers predictive of efficacy to the study combination.
OUTLINE: This is a dose-escalation study of dovitinib lactate.
Patients receive dovitinib lactate orally (PO) on days 1-5, 8-12, and 15-19, gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, and capecitabine PO twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks and then every 3 months for 1 year.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (dovitinib lactate, gemcitabine, and capecitabine) | Experimental | Patients receive dovitinib lactate PO on days 1-5, 8-12, and 15-19, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and capecitabine PO twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dovitinib lactate | Drug | Given PO |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose (MTD) is defined as the highest dose level at which less than 33% of patients experience study treatment-related dose limiting toxicities (DLT) | All toxicities and adverse events will be summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment. | First course, 21 days |
| Overall safety profile characterized by type, frequency, severity (according to National Cancer Institute [NCI] CTCAE version 4.0), timing, seriousness and relationship to study treatment | All toxicities and adverse events will be summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment. | Up to 30 days post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma pharmacokinetic parameters of dovitinib lactate, gemcitabine hydrochloride, capecitabine and their metabolites | Differences in biomarkers between responders and non-responders will be explored with frequencies and summary statistics. Biomarkers will be tested with Fisher's exact test. Pharmacokinetic parameters will be summarized for each cohort of patients. Comparison of pharmacokinetic parameters among the dose levels will be performed using non-parametric statistical methods for K-independent samples. Drug-drug interaction will be examined comparing pharmacokinetic parameters using nonparametric statistical methods. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Renuka Iyer | Roswell Park Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Roswell Park Cancer Institute | Buffalo | New York | 14263 | United States |
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| gemcitabine hydrochloride | Drug | Given IV |
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| capecitabine | Drug | Given PO |
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| laboratory biomarker analysis | Other | Correlative studies |
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| enzyme-linked immunosorbent assay | Other | Correlative studies |
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| pharmacological study | Other | Correlative studies |
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| Day 1 and 19 of course 1, day 8 of course 2 (Part A); day -14, day 19 of course 1,and day 8 of course 2 (Part B) |
| Solid tumor/dose-finding cohort: response rate, progression free survival | Tumor response will be defined according to the RECIST criteria version 1.1. | Up to 1 year |
| Pancreas cancer cohort: survival, response rate and progression free survival | Tumor response will be defined according to the RECIST criteria version 1.1. Overall survival for patients enrolled to Part B will be estimated using Kaplan-Meier method. | At 6 months |
| Pharmacodynamic effects of dovitinib lactate and Gem-Cap combination on vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptors (FGFR) dynamics in serum and tumor specimens | Day 1, 12, and 19 of course (Part A); days -14, -3, and days 12 and 19 of course 1 (Part B) |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C500007 | 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one |
| D000093542 | Gemcitabine |
| D000069287 | Capecitabine |
| D004797 | Enzyme-Linked Immunosorbent Assay |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D007124 | Immunoenzyme Techniques |
| D007118 | Immunoassay |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |
| D007163 | Immunosorbent Techniques |
| D007150 | Immunohistochemistry |
| D015336 | Molecular Probe Techniques |
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