Dovitinib Lactate, Gemcitabine Hydrochloride, and Capecitabine in Treating Patients With Advanced or Metastatic Solid Tumors, Pancreatic Cancer and Biliary Cancers
Adenocarcinoma of the Pancreas
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: dovitinib lactate
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Dovitinib (TKI258) in Combination With Gemcitabine and Capecitabine in Advanced Solid Tumors, Pancreatic Cancer and Biliary Cancers|
- 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) [ Time Frame: First course, 21 days ] [ Designated as safety issue: Yes ]All toxicities and adverse events will be summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.
- 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 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]All toxicities and adverse events will be summarized with frequencies and descriptive measures, and tabulated according to body system, severity and relation to treatment.
- Plasma pharmacokinetic parameters of dovitinib lactate, gemcitabine hydrochloride, capecitabine and their metabolites [ Time Frame: 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) ] [ Designated as safety issue: No ]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.
- Solid tumor/dose-finding cohort: response rate, progression free survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Tumor response will be defined according to the RECIST criteria version 1.1.
- Pancreas cancer cohort: survival, response rate and progression free survival [ Time Frame: At 6 months ] [ Designated as safety issue: No ]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.
- 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 [ Time Frame: Day 1, 12, and 19 of course (Part A); days -14, -3, and days 12 and 19 of course 1 (Part B) ] [ Designated as safety issue: No ]
|Study Start Date:||March 2012|
|Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dovitinib lactate, gemcitabine, and capecitabine)
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.
Drug: dovitinib lactate
Other Names:Drug: gemcitabine hydrochloride
Other Names:Drug: capecitabine
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: enzyme-linked immunosorbent assay
Other Name: ELISAOther: pharmacological study
Other Name: pharmacological studies
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01497392
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Wen Ma||Roswell Park Cancer Institute|