Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer
DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate that has demonstrated antineoplastic activities in human xenograft intracerebrally implanted tumor mouse models, acceptable preclinical toxicities in mouse, rat and dog models; and no behavioral cognitive impairment/neurotoxicities were noted in mouse and rat models.
The drug is ready for human use as an soy bean oil/lecithin/glycerin water emulsion, the latter which has been documented - chemically and biologically to be stable and safe. Patients are currently being enrolled and treated with the protocol.
Patients with advanced cancer, with or without central nervous system involvement will be eligible for enrollment, providing the required blood and other eligibility requirements are met.
Advanced Cancer With/Without Brain Involvement.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Protocol for the Safety and Tolerance of Intravenous 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer|
- Document maximum tolerated dose (MTD) & SLT [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- Document a toxicity profile for the drug [ Time Frame: one year ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2010|
|Study Completion Date:||November 2013|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
DM-CHOC-PEN is an intervention and will be dosed @ 39 mg/M2,escalated in 1-patient cohorts at 40% dosage.
DM-CHOC-PEN will be dosed @ 39 mg/M2, escalated in 1-patient cohorts at 40% dosage.
At the 1st DLT - expand to 3-6 patient cohorts/dose with escalations at 33% increments.
The MTD will be where 2 DLTs are noted and the study is discontinued.
Other Name: 4-Demethylcholesteryloxycarbonylpenclomedine
4-Demethylcholesterylpenclomedine(DM-CHOC-PEN)is a polychlorinated pyridine cholesteryl carbonate that has demonstrated complete remissions when administrated to mice bearing intracranially implanted human cancer xenografts (glioblastomas and breast cancers) and has acceptable preclinical toxicity profiles - mice, rats and dogs.
The drug is being administered intravenously once every 21 days as an infusion. The starting dose was 39 mg/M2 (based on 1/10 LD10 observed in mice and rats).
A modified accelerated dosing protocol of Simon, Freidlin, et al is in process to escalate dosage which will reduce the number of patients required and minimize ineffective doses. The protocol will result in one patient cohorts at 40% dosage escalations. When the 1st instance of a dose limiting toxicity (DLT) [grade - 3 or 4 toxicity] is observed, or the 2nd instance of a 1st course grade 2 toxicity of any type is observed, the cohort for that current dose level will be expanded to 3-6 patients and escalation will proceed at 33% increments.
During the entirety of the study, intra-patient escalation will be allowed. This will occur if the patient experiences are < grade 2 toxicity at the existing dose, if no > grade 2 toxicity was identified at the existing dose and no DLTs were noted at the higher dose level (if any patients had been escalated to that dose).
Continuation of therapy - Patients who experience stabilization, partial or complete remission while being treated will continue to receive the drug as per the last dose prior to identifying positive results at an every 3 weeks interval.
Discontinuation of therapy - progressive disease and/or toxicities.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01048008
|United States, Louisiana|
|Tulane University Medical School|
|New Orleans, Louisiana, United States, 70112|
|Principal Investigator:||Marcus L Ware, MD||Tulane University Medical School|