Solid TumorsPhase 1NCT01548924
Determination of Dose of Antiangiogenic Multitargeted DOVITINIB (TKI258) Plus Paclitaxel in Patients With Solid Tumors
A Phase 1 study testing Dovitinib and Dovitinib + Paclitaxel in people with Solid Tumors, run by Centro Nacional de Investigaciones Oncologicas CARLOS III at 3 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 76 years
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Dovitinib and Dovitinib + Paclitaxel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 3 sitesSpain
- Study dates
- Apr 2012to Aug 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 76 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
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- 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 exclusion criteria.
- 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
- Acute myocardial infarction in the three months prior to start of study treatment
- Other clinically significant heart disease (eg., Congestive heart failure [CHF], history of labile hypertension or poor compliance history of a pattern antihypertensive)
- Have uncontrolled infection.
- Diabetes mellitus (insulin or insulinoindependiente, needing chronic medication) with signs of clinically significant peripheral vascular disease.
- History of pericarditis, pleural effusion clinically important in the 12 months preceding or current ascites requiring two or more interventions per month (both increasing dose and for the expansion).
- clinically significant disorder of the hypothalamic-pituitary, adrenal or thyroid glands.
- History of acute or chronic pancreatitis from any cause.
- acute or chronic liver disease or chronic liver disease of any kind.
- Malabsorption syndrome or uncontrolled gastrointestinal toxicity (nausea, diarrhea, vomiting) than grade 2 NCI CTCAE.
- Any other serious medical or psychiatric disorder, acute or chronic, or analytical failure increases the risk associated with participation in the study or the drug test or interfere with the interpretation of study results and, in the opinion of investigator, prevent participation in it.
- Treatment with any of the drugs that can prolong the QT interval (Appendix C) or polymorphic ventricular tachycardia cause which can not be suspended or replaced by a different drug before the study treatment.
- Treatment with ketoconazole, erythromycin, carbamazepine, phenobarbital, rifampicin, phenytoin, quinidine two weeks before the baseline.
- Major surgery within 28 days before the start of study treatment, or not having recovered from the effects of a major operation.
- Diagnosis of HIV infection (HIV testing is not mandatory).
- History of another primary malignancy that currently has clinical or require active intervention.
- Patients with brain metastases detected by imaging studies (such as CT, MRI)
- Alcohol or drug abuse.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, 28049
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
MD Anderson Cancer Centre
Madrid
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Solid Tumors
- Being tested
- Dovitinib, Dovitinib + Paclitaxel
- Keywords
- Patients with malignant solid tumors of any histologically confirmed, not susceptible of cure, which have received the standard treatment available
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DovitinibDrug
Also called TKI-258
Orally Dovitinib once a day and a five-day regimen of administration and then two days resting, in cycles of 28 days.
Dovitinib + PaclitaxelDrug
Also called -Taxol, -TKI-258
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Priming Phase | Experimental | The study treatment begins with the period of seven days of priming Phase, which is administered in monoterapi dovitinib Receives: 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. Receives: Drug: Dovitinib + Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: After priming phase (7 days)
Secondary outcomes (1)
Pharmacokinetic interactions between paclitaxel and dovitinib
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
Measured: Baseline and end oftreatment phase, an espected average of 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionFeb 2013
- Study completionAug 2013
Why it stopped: Drug toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Nacional de Investigaciones Oncologicas CARLOS III
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario de Fuenlabrada, M.D. Anderson Cancer Center, Hospital Universitari de Bellvitge
- Responsible party
- Sponsor
- Investigators
- Miguel Ángel Quintela, M.D.,PhD, Study director, CNIORamón Colomer, M.D.,Ph.D, Principal investigator, CNIO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01548924
- Sponsor's protocol ID
- CNIO-BR-01-2011
- Status last verified
- Apr 2020
- First submitted
- 15 Feb 2012
- Last updated
- 17 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01548924
- Acronym / sponsor ID
- CNIO-BR-01-2011
- Conditions
- Solid Tumors
- Keywords
- Patients with malignant solid tumors of any histologically confirmed, not susceptible of cure, which have received the standard treatment available
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug toxicity
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Centro Nacional de Investigaciones Oncologicas CARLOS IIIUniversity, hospital or other
- Collaborators
- Hospital Universitario de Fuenlabrada, M.D. Anderson Cancer Center, Hospital Universitari de Bellvitge
- Study start
- Apr 2012
- Primary completion
- Feb 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 8 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Priming Phase | Experimental | Drug: DovitinibThe study treatment begins with the period of seven days of priming Phase, which is administered in monoterapi dovitinib |
| Treatment Phase | Experimental | Drug: Dovitinib + PaclitaxelThe 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. |
Who may qualify
- Ages
- 18 to 76 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (33 listed)
- 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:
- Have uncontrolled infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DovitinibAlso: TKI-258Orally Dovitinib once a day and a five-day regimen of administration and then two days resting, in cycles of 28 days. | Drug | Priming Phase |
| Dovitinib + PaclitaxelAlso: -Taxol, -TKI-258* 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. | Drug | Treatment Phase |
Primary outcome
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
1 secondary outcome
Pharmacokinetic interactions between paclitaxel and dovitinib
Time frame: Baseline and end oftreatment phase, an espected average of 16 weeks
Results and safety
The study was stopped early (reason given: Drug toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miguel Ángel Quintela, M.D.,PhD study director
CNIO
Ramón Colomer, M.D.,Ph.D principal investigator
CNIO
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dovitinib and Dovitinib + Paclitaxel in people with Solid Tumors, run by Centro Nacional de Investigaciones Oncologicas CARLOS III at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Drug toxicity). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: After priming phase (7 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2020.