This is a phase Ib dose escalation study of dovitinib given in combination with either gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. Patients with advanced solid tumors, for whom treatment with gemcitabine plus cisplatin or carboplatin would otherwise be warranted, will be enrolled. The dose of dovitinib will be escalated in successive cohorts using standard "3+3" dose escalation rules. Patients will continue treatment, in the absence of prohibitive toxicity, until disease progression. The study will define the recommended phase II dose of these combination regimens.
This is a phase Ib study of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin in patients with advanced solid tumors. This study will utilize standard 3+3 dose escalation rules to define the recommended phase II dose. Dose escalation will proceed independently in the two cohorts (cisplatin cohort: gemcitabine + cisplatin + dovitinib; carboplatin cohort: gemcitabine + carboplatin + dovitinib). Patients will receive treatment for up to 6 cycles, in the absence of toxicity, until disease progression Primary Objective: To determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus cisplatin or carboplatin. Secondary Objectives: * To determine the response rate to treatment as per Response Evaluation Criteria in Solid Tumors (RECIST) * To determine the toxicity of treatment at per the Common Terminology for Adverse Events (CTCAE v4) * To determine the pharmacokinetics of dovitinib in combination with gemcitabine plus cisplatin or carboplatin.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Cisplatin 70 mg/m2 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts
Gemcitabine 1000 mg/m2 IV on days 1 + 8 Carboplatin AUC 5 IV day 1 Dovitinib given orally on days 1-5, 8-12 and 15-19. Treatment will be recycled every 21-days. The dose of dovitinib will be escalated in successive cohorts
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Recommended phase II dose of combination regimen
The primary objectives of this study are to determine the recommended phase II dose of dovitinib given in combination with gemcitabine plus carboplatin or cisplatin.
Time frame: Within the first 21 days of treatment
Antitumor activity
A CT scan of the chest, abdomen, and pelvis will be performed after every 2 cycles (or sooner if there is evidence of disease progression) while on combination therapy until disease progression (eg, after cycle 2, after cycle 4, and after cycle 6). Response to treatment will be determined using RECIST.
Time frame: After every 2 cycles (42 days) of combination therapy up to 3 years
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