Clinical trial NCT01976910: Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer"
Official title: A Protocol for the Safety and Tolerance of Intravenous 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Keywords: Advanced cancers
Brain Neoplasms, Malignant, Primary
Brain Tumor, Recurrent
Advanced cancer
Lead sponsor: DEKK-TEC, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-11-06
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Hyperbilirubinemia
timeFrame: 3-year
Secondary outcomes:
measure: Document a MTD
timeFrame: 2-3 years
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane University Medical School
state: Louisiana
Study officials:
affiliation: Tulane University Medical School
name: Marcus L Ware, MD
role: PRINCIPAL_INVESTIGATOR
References: