Determination of Dose of Antiangiogenic Multitargeted DOVITINIB (TKI258) Plus Paclitaxel in Patients With Solid Tumors

NCT01548924 | Terminated Phase 1 DMC

• 1 other identifier: CNIO-BR-01-2011
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

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.

Conditions

Solid Tumors

Keywords

Patients with malignant solid tumors of any histologically confirmed, not susceptible of cure, which have received the standard treatment available

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Determine the maximum tolerated dose (MTD), the recommended dose for Phase 2 and the safety and tolerability in combination with paclitaxel dovitinib weekly

  After priming phase (7 days)

Secondary Outcomes (1)

• Pharmacokinetic interactions between paclitaxel and dovitinib

  Baseline and end oftreatment phase, an espected average of 16 weeks

Study Arms (2)

Priming Phase

EXPERIMENTAL

The study treatment begins with the period of seven days of priming Phase, which is administered in monoterapi dovitinib

Drug: Dovitinib

Treatment Phase

EXPERIMENTAL

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.

Drug: Dovitinib + Paclitaxel

Interventions

Dovitinib DRUG

Orally Dovitinib once a day and a five-day regimen of administration and then two days resting, in cycles of 28 days.

Also known as: TKI-258

Priming Phase

Dovitinib + Paclitaxel DRUG

* 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.

Also known as: -Taxol, -TKI-258

Treatment Phase

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• clinically significant resting bradycardia (\< 50 bpm)
• Uncontrolled hypertension (systolic pressure ≥ 150 mm Hg or diastolic pressure ≥ 100 mm Hg, with or without antihypertensive medication).
• QTc \> 480 ms on ECG screening
• Right bundle branch block over left anterior hemiblock (bifascicular block)
• Angina pectoris in the three months prior to start of study treatment

Sponsors & Collaborators

• Centro Nacional de Investigaciones Oncologicas CARLOS III: lead
• Hospital Universitario de Fuenlabrada: collaborator
• M.D. Anderson Cancer Center: collaborator
• Hospital Universitari de Bellvitge: collaborator

Study Sites (3)

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, 28049, Spain

Location

MD Anderson Cancer Centre

Madrid, Spain

Location

MeSH Terms

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Miguel Ángel Quintela, M.D.,PhD

  CNIO

  STUDY DIRECTOR

• Ramón Colomer, M.D.,Ph.D

  CNIO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2012
• First Posted: March 8, 2012
• Study Start: April 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: August 1, 2013
• Last Updated: April 17, 2020

Record last verified: 2020-04

Locations

ES (3)