MC# 19-34 - A Phase II Trial: Safety and Tolerance of Intravenous 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Adolescent and Young Adult (AYA) Subjects with Advanced Malignancies Involving the Central Nervous System (CNS)

  • Agent(s): DM-CHOC-PEN
  • Disease Type(s): CNS involved Solid Tumors
  • Phase(s): II
  • Drug Classification(s): Targeted Therapy, Gene Therapy
  • Molecular Target(s): DNA at the N7 guanine position

Mechanism of Action

DM-CHOC-PEN is a cholesterol carbonate derivative of 4-demethylpenclomedine (DM-PEN).  The carbonium moiety binds to and alkylates DNA at the N7 guanine position, thereby causing DNA crosslinks, preventing DNA replication, inhibiting cellular proliferation and triggering apoptosis.  This agent is able to cross the blood brain barrier (BBB).

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of DM-CHOC-PEN
  • If DM-CHOC-PEN prevents or delays tumor growth or shrinks existing tumors
  • How fast DM-CHOC-PEN is removed from your bloodstream
Inclusion Criteria
  • All subjects must have histological evidence of a solid malignant tumor with convincing clinical, radiographic or isotopic evidence of cancer that has failed to respond to standard therapies.  All enrollees must have MRI evidence of CNS involvement.  Presence of measurable disease is desired, but if a subject does not have measurable disease, they must have evaluable disease for study entry.
  • Adult subjects including those that require a Legally Representative (LAR) or Legal parents or guardians of the adolescent subjects (unless the subject has been emancipated or can sign for his or her self) must understand the nature of the study and be willing to sign an informed consent that complies with the investigator/DEKK-TEC policies and approved by the trial center’s Human Investigation Review Committee (IRC)
  • All subjects must have a Lansky Play or if >16 y/o, a Karnofsky performance score: >70%
  • All subjects 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).  Subjects who have received a nitrosourea type drug or ipilumimab must have had no treatment within the last six weeks.
  • Measurable lesions are not required for admittance to the study – but evaluable disease is required
  • Age limitation – 15 to 39 years of age
  • Gender is not a criterion
  • Subjects should have a hepatic function (alkaline phosphatase, AST and ALT) – WNL and renal functions with serum creatine – 1.5 x UNL
  • Subjects should have adequate bone marrow function defined as a peripheral WBC count equal to or greater than 1,500/mm3 with an ANC >1,000/mm3 and a platelet count equal to or greater than 75,000/mm3
  • Subjects must be medically, psychologically and neurologically stable and have triplicate baseline ECG’s with a mean QTc interval <500 ms and >300 ms and neither a history of congenital prolonged or short QT syndrome.  Patients with a history of cardiac disease must be stable.
Exclusion Criteria
  • Hematology
    •  WBC <1,500 mm3, ANC <1,000 mm3
    •  Platelets <75,000 mm3
  • Liver Function
    • If bilirubin, AST, and/or ALT are >ULN
  • Renal Function – Creatinine >1.5 x upper limits of normal
  • Serum esterase level - >2 SE units/mL
  • Subjects with concurrent severe and/or uncontrolled medical, psychiatric, or social conditions that could compromise the safety or compliance of treatment are not eligible
  • 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 for at least 3 months after the last dose of study drug.  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 or soy products
  • Subjects are not allowed to take the following medications while on study:

CYP450 Inducer/inhibitors

QT/QTc Interval Associated

Fluconazole

All Anti-arrhythmia drugs (incl. aminodarone)

Erythromycin

Quinolones

Phenobarbital

Ketoconazole

Verapamil

Azithromycin, Phenothiazine

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/show/NCT03668847

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Re: MC# 19-34