Phase I/II Randomized Clinical Trial of Neoadjuvant Paclitaxel Versus Priming With BIBF 1120 BIBF 1120 Followed by Plus Paclitaxel in Breast Cancer With HER-2 Negative Correlative Proteomic Studies. and Dynamic Image
Overview
- Phase
- Phase 1
- Intervention
- Dovitinib
- Conditions
- Solid Tumors
- Sponsor
- Centro Nacional de Investigaciones Oncologicas CARLOS III
- Enrollment
- 13
- Locations
- 3
- Primary Endpoint
- Maximum tolerated dose (MTD)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
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.
- •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:
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 TKI
- •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).
Arms & Interventions
Priming Phase
The study treatment begins with the period of seven days of priming Phase, which is administered in monoterapi dovitinib
Intervention: Dovitinib
Treatment Phase
The phase of treatment with two drugs (paclitaxel dovitinib more fixed dose of 80 mg/m2 per week) will begin after a washout period of seven days after the priming phase.
Intervention: Dovitinib + Paclitaxel
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD)
Time Frame: 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 Outcomes
- Pharmacokinetic interactions between paclitaxel and dovitinib(Baseline and end oftreatment phase, an espected average of 16 weeks)