Ignite Creation Date:
2024-05-06 @ 12:21 AM
Last Modification Date:
2024-10-26 @ 10:48 AM
Study NCT ID:
NCT01553071
Status:
TERMINATED
Last Update Posted:
2022-03-31
First Post:
2012-03-07
Brief Title:
Phase I Trial of IV Fenretinide 4-HPR Plus IV Safingol for Patients With Relapsed Malignancies
Sponsor:
South Plains Oncology Consortium
Organization:
South Plains Oncology Consortium
Study Overview
Official Title:
Phase I Trial of Intravenous Fenretinide 4-HPR Plus Intravenous Safingol for Patients With Relapsed Malignancies
Status:
TERMINATED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
drug supply issues during COVID-19
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In preclinical studies the anti-cancer efficacy of fenretinide a synthetic retinoid that causes cytotoxicity by mechanisms which include increased intracellular dihydroceramides has been shown to be enhanced by safingol a stereochemical-variant dihydroceramide precursor This phase I study represents the first clinical trial employing this promising combination The drug administration schedule fenretinide given on Days 1-5 safingol given on Days 1-2 of each 21-day cycle reflects the in vitro observation that tumor cell exposure to safingol increased fenretinide efficacy both during and after safingol administration The total dose of fenretinide 4600 mgm2 over 5 days represents a 30 total dose reduction from the single agent MTD dose of 1280 mgm2day x 5 days determined on the PhI-42 study This fenretinide dose is expected to produce plasma levels in the 30s M This dose reduction has been employed to reduce the potential for overlapping hepatic toxicities between these two agents
The administration of a reduced fenretinide dose on Day 1 600 mgm2 on Day 1 escalated to 1000 mgm2day on Days 2-5 has been selected due to earlier observations that initial exposure to the soy bean oil vehicle in the fenretinide emulsion may induce endogenous lipases thereby permitting tolerance of higher total doses fenretinide emulsion subsequently administered The starting dose of safingol in this study 210 mgm2day x 2 days 420 mgm2 total corresponds to 50 of the recommended Phase II safingol dose bolus determined in the Schwartz et al Phase I study of safingol plus cisplatin 60 mgm2 the MTD of single-agent intravenous emulsion safingol was not reached in the Phase I safingol run-in monotherapy portion of this study and was selected to provide an adequate safety margin against the potential for overlapping toxicities such as hepatic transaminitis
The study has been designed to optimize the safety of this novel combination Treatment will be administered in the inpatient setting Central venous access will be mandated to avoid the potential for hemolysis and thrombophlebitis associated with the preclinical peripheral administration of a previous safingol formulation in rats To reduce the incidence of hypertriglyceridemia a revised fenretinide delivery schedule will be employed Patients will also be encouraged to maintain a low-fat diet during fenretinide administration Serum triglycerides will be monitored every 12 hours To monitor for cardiac toxicity which was noted in canine studies at the highest dose of safingol plus fenretinide tested serum troponin T levels will be monitored daily To limit the potential for hepatotoxicity resulting from a possible drug interaction observed between intravenous fenretinide ceftriaxone and acetaminophen in a pediatric patient the concurrent administration of ceftriaxone or acetaminophen with the fenretinide emulsion infusion will be prohibited
The administration of a reduced fenretinide dose on Day 1 600 mgm2 on Day 1 escalated to 1000 mgm2day on Days 2-5 has been selected due to earlier observations that initial exposure to the soy bean oil vehicle in the fenretinide emulsion may induce endogenous lipases thereby permitting tolerance of higher total doses fenretinide emulsion subsequently administered The starting dose of safingol in this study 210 mgm2day x 2 days 420 mgm2 total corresponds to 50 of the recommended Phase II safingol dose bolus determined in the Schwartz et al Phase I study of safingol plus cisplatin 60 mgm2 the MTD of single-agent intravenous emulsion safingol was not reached in the Phase I safingol run-in monotherapy portion of this study and was selected to provide an adequate safety margin against the potential for overlapping toxicities such as hepatic transaminitis
The study has been designed to optimize the safety of this novel combination Treatment will be administered in the inpatient setting Central venous access will be mandated to avoid the potential for hemolysis and thrombophlebitis associated with the preclinical peripheral administration of a previous safingol formulation in rats To reduce the incidence of hypertriglyceridemia a revised fenretinide delivery schedule will be employed Patients will also be encouraged to maintain a low-fat diet during fenretinide administration Serum triglycerides will be monitored every 12 hours To monitor for cardiac toxicity which was noted in canine studies at the highest dose of safingol plus fenretinide tested serum troponin T levels will be monitored daily To limit the potential for hepatotoxicity resulting from a possible drug interaction observed between intravenous fenretinide ceftriaxone and acetaminophen in a pediatric patient the concurrent administration of ceftriaxone or acetaminophen with the fenretinide emulsion infusion will be prohibited
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