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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
DEKK-TEC, Inc.
ClinicalTrials.gov Identifier:
NCT01048008
First received: January 11, 2010
Last updated: January 9, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancer With/Without Brain Involvement.
Drug: DM-CHOC-PEN
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by DEKK-TEC, Inc.:

Primary Outcome Measures:
  • Document maximum tolerated dose (MTD) & SLT [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Document a toxicity profile for the drug [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: September 2010
Study Completion Date: November 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 4-Demethylcholesteryloxycarbonylpenclomedine

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01048008

Locations
United States, Louisiana
Tulane University Medical School
New Orleans, Louisiana, United States, 70112
Sponsors and Collaborators
DEKK-TEC, Inc.
Investigators
Principal Investigator: Marcus L Ware, MD Tulane University Medical School
  More Information

No publications provided

Responsible Party: DEKK-TEC, Inc.
ClinicalTrials.gov Identifier: NCT01048008     History of Changes
Other Study ID Numbers: DTI-021, 5R43CA132257-02
Study First Received: January 11, 2010
Last Updated: January 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by DEKK-TEC, Inc.:
Glioblastoma multiforme
Advanced cancers
Brain Neoplasms, Malignant, Primary
Brain Tumor, Recurrent
Advanced cancer

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014