Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 1/1/2014 |
| Start Date: | September 2010 |
| End Date: | July 2013 |
| Contact: | Lee R Morgan, MD, PhD |
| Email: | lrm1579@aol.com |
| Phone: | 504-583-6135 |
A Protocol for the Safety and Tolerance of Intravenous 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.
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.
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.
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.
Inclusion Criteria:
- All patients must have histological evidence of a solid malignant tumor
(hematological malignancies are excluded) with convincing clinical, radiographic or
isotopic evidence of cancer, for which no effective proven treatment exists. CNS
associated tumors are preferred, but not required. Patients must sign an informed
consent that complies with the investigator/DEKK-TEC policies and approved by a Human
Investigation Review Committee.
- All patients must have a projected survival time of at least 12 weeks and a Karnofsky
performance score: >60% (or Zubrod score of >2).
- All patients must be off previous chemo- and/or radiotherapy for at least three (3)
weeks prior to entrance into the study and have recovered from any toxic effects
induced by such treatment(s). Patients who have received a nitrosourea type drug
must have had no treatment within the last six weeks.
- Measurable lesions are not required for admittance to the study - but are desirable.
- Age initiated after limitation - 18 years or older. A separate pediatric study is
proposed to evaluate tolerance to the drug in children.
- Gender is not a criterion.
Exclusion Criteria:
- Hematology WBC <4,000 mm3 Platelets <100,000 mm3
- Liver Function If bilirubin, AST, and/or ALT are >ULN
- Renal Function Creatinine >1.5 mg%
- Cardiovascular Acute myocardial infarction Congestive heart failure - (NYHA criteria
for uncontrolled) Clinically significant cardiac arrhythmias - uncontrolled
- Concomitant chemotherapy or radiotherapy is not permitted.
- Pregnant or lactating females are excluded. Women of childbearing age, and their
sexual partners, must use an effective contraception program. Males who are having
sexual relations with women capable of child bearing must use birth control while on
the study and for 3-months after the last dose of the study drug.
- Allergies to eggs, lecithin or soy products.
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