Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer" (DM-CHOC-PEN)

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.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: DM-CHOC-PEN

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 4-DM-CHOC-PEN; DM-CHOC-PEN is an intervention and 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.	Drug: DM-CHOC-PEN; 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 Names: 4-Demethylcholesteryloxycarbonylpenclomedine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperbilirubinemia	Document hepatic toxicity.	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Document a MTD	Patients were treated in cohorts from 39-111 mg/m2 single IV doses. Hepatic toxicity was a limiting factor for patients w/ liver disease. Phase II trials will be 2-tier - w/ liver involvement and without,.	2-3 years

Collaborators and Investigators

• Sponsor: DEKK-TEC, Inc.
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (ESTIMATE): November 6, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 4, 2020
• Last Update Submitted That Met QC Criteria: July 31, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Advanced cancer; Brain Tumor, Recurrent; Advanced cancers; Brain Neoplasms, Malignant, Primary
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 68,876; 5R43CA132257-02 (NIH)