Solid Tumors
Conditions
Keywords
Patients with malignant solid tumors of any histologically confirmed, not susceptible of cure, which have received the standard treatment available
Brief summary
The investigators plan to study the determination of the dose and the combination of antiangiogenic effect of dovitinib and cytotoxic activity of weekly paclitaxel in different types of malignant tumors.
Detailed description
This is an open label,multicenter, Phase I dose escalation study with a phase dovitinib alone for the pharmacokinetic profile and a treatment phase to evaluate the safety and tolerability of oral(po)dovitinib with paclitaxel administered intravenously (iv) (80 mg/m2 on days 1, 8, 15 and 21 every 4 weeks) in patients with malignant tumors of any histologically confirmed, not susceptible of cure, which have been treated available reference.
Interventions
DRUGDovitinib
Orally Dovitinib once a day and a five-day regimen of administration and then two days resting, in cycles of 28 days.
DRUGDovitinib + Paclitaxel
* Paclitaxel (80 mg/m2) : 1, 8, 15 and 21. * Dovitinib (100 mg, 200 mg,300 mg, 400 mg or500 mg; it depends on the level of the Phase 1 study in each patient): five days of treatment / two days off. Each cycle will last for 28 days.
Sponsors
Hospital Universitario de Fuenlabrada
M.D. Anderson Cancer Center
Hospital Universitari de Bellvitge
Centro Nacional de Investigaciones Oncologicas CARLOS III
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
* Have signed the informed consent of study and be willing to undergo an image-guided biopsy and blood sampling for FC. * Men or women over 18 years. * Patients with solid tumors locally advanced or metastatic confirmed by histological methods or cytological, not susceptible of cure, who received the standard treatment available. Participation of patients with more active malignancy. * measurable or nonmeasurable disease as version 1.1. of RECIST * Class 0 to 2 of the ECOG * Have at least four weeks elapsed since the last normal or experimental antitumor treatment (six weeks for BCNU, CCNU or mitomycin C) * Have recovered of any toxicity (except alopecia) to grade 0 or 1 according to common terminology criteria for adverse events from the National Cancer Institute (NCI CTCAE, version 4.0). * Life expectancy of three months. * Participation of patients with more active malignancy. * The baseline analytical data required are: * Absolute neutrophil count (ANC) ≥ 1.500/mm3 \[1.5 x 109/l\] * Platelets ≥ 75.000/mm3 \[75 x 109/l\] * Hemoglobin ≥ 8.0 g / dL \[80 g/l\] * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) * Bilirubin ≤ 1.5 x ULN. * AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN (with or without liver metastases) * Concentration of electrolytes: * Potassium \< LIN (3.0 mmol/l) or \> ULN (5.5 mmol/l) * Sodium \< LIN (130 mmol/l) or \> ULN (150 mmol/l) * Women of childbearing potential must have a negative pregnancy test within 7 days prior to inclusion in the study.
Exclusion criteria
* Concomitant treatment with another investigational drug within 28 days before the baseline visit. * Have been treated with dovitinib. * Women of childbearing age and biologically capable of conceiving not using two contraceptive methods very effective. Highly effective contraceptive methods (such as condom with spermicide, diaphragm with spermicide, intrauterine device) should be used by both sexes during the study and maintained for 8 weeks after the end of study treatment. Oral contraceptives, implantable, or injectable may be affected by interactions with cytochrome P450, so not considered effective in this study. Women of childbearing age, defined as sexually mature those who have not had a hysterectomy or who reached natural menopause less than 12 consecutive months (i.e., who have had menses at some time during the last 12 months) must have a negative pregnancy test within 72 hours before the start of treatment with TKI258. * Clinically significant heart disease (class III or IV New York Heart Association) or impaired cardiac function, comprising any of the following: * LVEF less than 50% or lower limit of normal (whichever is greater) to evaluate two echocardiography (ECO), or below 45% or lower limit of normal (whichever is greater) on ventriculography equilibrium radionuclide (MUGA) * left bundle branch block * Use of cardiac pacemaker must * Congenital Long QT Syndrome * History or presence of ventricular tachyarrhythmia * Presence of unstable atrial fibrillation (ventricular rate\> 100 bpm). * Patients with stable atrial fibrillation may participate provided they do not meet any of the other cardiac
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | After priming phase (7 days) | Determine the maximum tolerated dose (MTD), the recommended dose for Phase 2 and the safety and tolerability in combination with paclitaxel dovitinib weekly |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic interactions between paclitaxel and dovitinib | Baseline and end oftreatment phase, an espected average of 16 weeks | To evaluate the pharmacokinetic interactions between paclitaxel and dovitinib. Establish the sampling circuit and molecular diagnostic procedures for future expansion cohort at the recommended dose for Phase 2, focusing on patients with amplifications or mutations of drug targets. Other criteria for safety assessment will be the number of cycles and dose intensity of each component of the treatment regimen, changes in vital signs and results of laboratory tests during and after administration of paclitaxel and dovitinib |
Countries
Spain
Outcome results
None listed