A Protocol for the Safety and Tolerance of Intravenous 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer
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.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Document maximum tolerated dose (MTD) & SLT
Marcus L Ware, MD
Tulane University Medical School
United States: Food and Drug Administration
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