Ignite Creation Date:
2024-05-06 @ 12:19 AM
Last Modification Date:
2024-10-26 @ 10:48 AM
Study NCT ID:
NCT01548170
Status:
COMPLETED
Last Update Posted:
2012-03-08
First Post:
2011-12-23
Brief Title:
To Assess the Interaction Between Sunitinib and Ketoconazole to Reduce the Dose and Cost of Sunitinib
Sponsor:
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Organization:
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Study Overview
Official Title:
A Phase I Pilot Dose Finding Clinical Trial to Assess the Interaction Between Sunitinib and Ketoconazole to Reduce the Dose and Cost of Sunitinib for National Health System
Status:
COMPLETED
Status Verified Date:
2012-03
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:
Sunitinib is an ATP competitive tyrosine kinase inhibitor of several membrane receptors including VEGFR-1 -2 and -3 PDGFR-α and -β c-KIT CSF-1R FLT-3 and RET Through this molecular mode of action sunitinib is able to avoid tumoral angiogenesis and proliferation Sunitinib is already approved by the FDA EMEA and AEMPS for the treatment of patients with metastatic renal cell carcinomas and those with metastatic gastrointestinal stromal tumors GIST with progression or intolerance to imatinib
Suntinib has recently reported to be superior than placebo in terms of response rate 93 vs 0 p005 progression free survival 114 vs 55 months HR 041p005 and overall survival HR 040p005 when administered in a phase 3 trial to patients with advanced pancreatic neuroendocrine tumors NETs
Sunitinib is an expensive drug that drains the budget of health public system therefore it demands a rational drug use
Sunitinib is metabolized by CYP3A4 that belongs to the P450 cytochrome system in the liver Most of the drug is eliminated in faeces and only 16 by urine Sunitinib has no food-effect when taken with meals Pharmacokinetics parameters did not differ between cancer patients and healthy volunteers
Houk et al Showed that the area under the curve of plasmatic concentration of sunitinib and its active metabolite did correlate with clinical outcome In other words the higher plasma concentration area under the curve the highest rates of radiological response progression free and overall survival rates
Ketoconazol is an antifungal drug that inhibits the CY3A4 inducing an elevation of peak plasma levels of other drugs administered simultaneously and that are metabolized by the same system In the labeling sheet of sunitinib it is said that ketoconazol induced a 49 and 51 of increase of plasmatic sunitinib Cmax y AUC0- when both drugs were administered together This fact makes that the investigatorspropose that by administering both drugs simultaneously the investigators could reduce sunitinib dose by a lower metabolization with similar plasma concentration The dose reduction would impact in drug cost
Here the investigators propose to determine the most optimal combination dose of sunitinib 25 mg or 375 mg and ketoconazol 200mg o 400mg by which the investigators could have plasmatic bioequivalent concentrations compared with single dose of sunitinib 50mg
Each volunteer will be assigned to a treatment arm Arm A and Arm B Volunteers included in Arm A will take sunitinib 50 mg sunitinib 375 mg ketoconazole 200 mg and sunitinib 375 mg 400 mg ketoconazole Volunteers included in Arm B will take sunitinib 50 mg sunitinib 25 mg ketoconazole 200 mg and sunitinib 25 mg 400 mg ketoconazole
Suntinib has recently reported to be superior than placebo in terms of response rate 93 vs 0 p005 progression free survival 114 vs 55 months HR 041p005 and overall survival HR 040p005 when administered in a phase 3 trial to patients with advanced pancreatic neuroendocrine tumors NETs
Sunitinib is an expensive drug that drains the budget of health public system therefore it demands a rational drug use
Sunitinib is metabolized by CYP3A4 that belongs to the P450 cytochrome system in the liver Most of the drug is eliminated in faeces and only 16 by urine Sunitinib has no food-effect when taken with meals Pharmacokinetics parameters did not differ between cancer patients and healthy volunteers
Houk et al Showed that the area under the curve of plasmatic concentration of sunitinib and its active metabolite did correlate with clinical outcome In other words the higher plasma concentration area under the curve the highest rates of radiological response progression free and overall survival rates
Ketoconazol is an antifungal drug that inhibits the CY3A4 inducing an elevation of peak plasma levels of other drugs administered simultaneously and that are metabolized by the same system In the labeling sheet of sunitinib it is said that ketoconazol induced a 49 and 51 of increase of plasmatic sunitinib Cmax y AUC0- when both drugs were administered together This fact makes that the investigatorspropose that by administering both drugs simultaneously the investigators could reduce sunitinib dose by a lower metabolization with similar plasma concentration The dose reduction would impact in drug cost
Here the investigators propose to determine the most optimal combination dose of sunitinib 25 mg or 375 mg and ketoconazol 200mg o 400mg by which the investigators could have plasmatic bioequivalent concentrations compared with single dose of sunitinib 50mg
Each volunteer will be assigned to a treatment arm Arm A and Arm B Volunteers included in Arm A will take sunitinib 50 mg sunitinib 375 mg ketoconazole 200 mg and sunitinib 375 mg 400 mg ketoconazole Volunteers included in Arm B will take sunitinib 50 mg sunitinib 25 mg ketoconazole 200 mg and sunitinib 25 mg 400 mg ketoconazole
Detailed Description:
This is a phase I pilot open randomized parallel and cross-over trial to assess the interaction between three different dose levels of sunitinib 50 mg 375 mg and 25 mg and two dose levels of ketoconazole 200 mg and 400 mg in 12 healthy volunteers 6 voluunteers in each group of treatment Each volunteer will be assigned to a treatment arm Arm A and Arm B Volunteers included in Arm A will take sunitinib 50 mg sunitinib 375 mg ketoconazole 200 mg and sunitinib 375 mg 400 mg ketoconazole Volunteers included in Arm B will take sunitinib 50 mg sunitinib 25 mg ketoconazole 200 mg and sunitinib 25 mg 400 mg ketoconazole
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2010-023739-41 | EUDRACT_NUMBER | None | None |