Ignite Creation Date:
2024-05-05 @ 11:14 PM
Last Modification Date:
2024-10-26 @ 10:30 AM
Study NCT ID:
NCT01283945
Status:
COMPLETED
Last Update Posted:
2020-01-03
First Post:
2011-01-25
Brief Title:
Study of Oral Lucitanib E-3810 a Dual VEGFR-FGFR Tyrosine Kinase Inhibitor in Patients With Solid Tumors
Sponsor:
Institut de Recherches Internationales Servier
Organization:
Servier
Study Overview
Official Title:
An Open-Label Dose-escalation Phase IIIa Study to Determine the Maximum Tolerated Dose Recommended Dose Efficacy Pharmacokinetics and Pharmacodynamics of the Dual VEGFR-FGFR Tyrosine Kinase Inhibitor E-3810 Given Orally as Single Agent to Patients With Advanced Solid Tumours
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Co-selective inhibition of VEGFRs and FGFR has the potential benefit of blocking the two most relevant players in tumor angiogenesis and simultaneously targeting proliferation in FGF-driven tumors Lucitanib is a novel dual-targeted small molecule inhibitor of VEGFR1 2 3 and FGFR1 showing strong anti-angiogenic and anti-tumor activity in preclinical models at well-tolerated oral doses with a favorable pharmacokinetic profile These properties make it an attractive candidate for development in humans
This is an open-label uncontrolled non-randomized PhaseIIIa study and its primary objective is to determine the Maximum Tolerated Dose MTD of Lucitanib administered orally once daily on a continuous schedule over the initial 28-day cycle
Secondary objectives are to determine the safety profile pharmacokinetics pharmacodynamics and antitumour activity of Lucitanib given as a single agent to adult patients with advanced solid tumours
The study consists of two phases a dose escalation phase followed by a dose-expansion phase at the identified Recommended Dose RD Eligible patients have histologically or cytologically confirmed locally advanced or metastatic solid tumours relapsed or refractory to standard therapy For the dose expansion patients should have tumours bearing FGFR1 or 11q 12-14 amplification assessed by FISH or CGH array or sensitive to antiangiogenic treatment These latter are defined as patients who have relapsed after having experienced stable disease lasting at least six months or partial response with prior treatment with an approved antiangiogenic regimen or patients with tumour types known to be potentially responsive to antiangiogenic agents but without such pretreatment if no antiangiogenic agents were approved andor available for that specific condition eg thyroid cancer thymic carcinoma
Serial safety assessments including evaluation of symptoms physical examination and blood and urine laboratory analyses are performed throughout the study Cardiac functions and blood pressure are monitored in consultation with a cardiologist PK parameters are determined on plasma samples collected during the first 4-week cycle and analyzed using a validated LC-MSMS method Correlative studies include i quantitative assessment of the effects of E-3810 on tumor vasculature by DCE-MRI and DCE-US imaging ii assay of angiogenesis biomarkers ie soluble VEGFR2 VEGFR1 VEGF bFGF Collagen IV FGF23 and PIGFby ELISA and circulating endothelial and progenitors cells CEC and CEP Tumor response is based on imaging according to RECIST circulating tumor cells CTC are measured by the immunomagnetic CellSearch method
In patients with tumours bearing FGFR1 amplifications the efficacy of Lucitanib will be formally tested according to a phase IIa design one-stage Flaming design H0005 H1030 power 080
This is an open-label uncontrolled non-randomized PhaseIIIa study and its primary objective is to determine the Maximum Tolerated Dose MTD of Lucitanib administered orally once daily on a continuous schedule over the initial 28-day cycle
Secondary objectives are to determine the safety profile pharmacokinetics pharmacodynamics and antitumour activity of Lucitanib given as a single agent to adult patients with advanced solid tumours
The study consists of two phases a dose escalation phase followed by a dose-expansion phase at the identified Recommended Dose RD Eligible patients have histologically or cytologically confirmed locally advanced or metastatic solid tumours relapsed or refractory to standard therapy For the dose expansion patients should have tumours bearing FGFR1 or 11q 12-14 amplification assessed by FISH or CGH array or sensitive to antiangiogenic treatment These latter are defined as patients who have relapsed after having experienced stable disease lasting at least six months or partial response with prior treatment with an approved antiangiogenic regimen or patients with tumour types known to be potentially responsive to antiangiogenic agents but without such pretreatment if no antiangiogenic agents were approved andor available for that specific condition eg thyroid cancer thymic carcinoma
Serial safety assessments including evaluation of symptoms physical examination and blood and urine laboratory analyses are performed throughout the study Cardiac functions and blood pressure are monitored in consultation with a cardiologist PK parameters are determined on plasma samples collected during the first 4-week cycle and analyzed using a validated LC-MSMS method Correlative studies include i quantitative assessment of the effects of E-3810 on tumor vasculature by DCE-MRI and DCE-US imaging ii assay of angiogenesis biomarkers ie soluble VEGFR2 VEGFR1 VEGF bFGF Collagen IV FGF23 and PIGFby ELISA and circulating endothelial and progenitors cells CEC and CEP Tumor response is based on imaging according to RECIST circulating tumor cells CTC are measured by the immunomagnetic CellSearch method
In patients with tumours bearing FGFR1 amplifications the efficacy of Lucitanib will be formally tested according to a phase IIa design one-stage Flaming design H0005 H1030 power 080
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None