DM-CHOC-PEN for Brain Tumors in AYA Subjects
Condition: Advanced Cancer; Brain Metastases
MeSH terms: Brain Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a polychlorinated pyridyl
      cholesterol carbonate that is lipophilic, electrically neural, crosses the blood brain
      barrier (BBB), ability to localize in intracranial tumor tissue, lacks neurotoxicity and not
      transported out of the brain via Pgp (p-glycoprotein). DM-CHOC-PEN has completed a Phase I
      Adolescent and Young Adult (AYA) trial in humans, some of which possessed primary and
      secondary tumors involving the brain. Complete remissions in both primary (astrocytoma, GBM)
      and metastatic lung cancers were reported.

      This Phase II trial is closed for adolescent and young adults (AYA) subjects with advanced
      cancer - brain involvement is required.
    

Detailed description: 
      The primary goal of this Phase II AYA oncology clinical trial was to evaluate the safety and
      efficacy of 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), as anticancer
      therapy in AYA individuals with advanced cancer involving the central or spinal nervous
      system (CNS & SNS).

      DM-CHOC-PEN is a polychlorinated pyridine cholesteryloxycarbonate that crosses the blood
      brain barrier (BBB), accumulates in CNS tumor tissue in humans and has produced objective
      responses, with acceptable/reversible hepatic toxicities (in patients with prior liver
      disease) and no evidence of hematological, renal, neuro-toxicities with improved quality of
      life and overall survival in adolescent, young adult and adult Phase I/II clinical trials -
      IND - 68,876.

      The FDA has supported the Phase II clinical trial designed to identify safety and efficacy in
      AYA cancers subjects and the trial has been completed with acceptable toxicity and MTDs
      identified.

      Almost 700,000 people in the US are living with tumors involving the CNS or spinal nervous
      system (SNS) tumors. Nearly 15% of these tumors involve the adolescent/young adult (AYA)
      population, aged 15-39 years of age. It is predicted that 10,617 AYA individuals will be
      diagnosed with brain or CNS tumors resulting in 434 deaths this year in the US. Trends in CNS
      tumors have sharply increased since 1989 for AYA individuals with a history of cancer, who
      appeared to have 'beaten the odds', only to have a re-occurrence from cancer involving the
      CNS after years of remission; the most common types of cancer in AYA individuals are -
      melanoma, leukemia and sarcomas. This group of individuals deserves special attention.

      For males and female individuals <20 years of age, primary brain and secondary cancers of the
      CNS and spinal nervous system (SNS) are the most common causes of death from cancer and in
      the 20-39 year age group the first cause of cancer-related deaths in males and the fifth
      cause of cancer-related deaths in females. The incidence and histology of cancer types does
      vary according to subject age.

      A critical component in designing an agent that will cross the protective blood brain barrier
      (BBB) is that the agent must be readily transported intracerebrally, does not produce local
      irritation/neurotoxicity and is not recycled back into the general circulation. After IV
      administration DM-CHOC-PEN readily penetrates the BBB, is not a substrate for the transporter
      protein P-glycoprotein (P-gp) and has shown anticancer activity in CNS tumors. The effective
      transport of DM-CHOC-PEN into CNS tumors in adults without neurotic behavioral alterations
      and associated events supports the drug's use in children with CNS tumors at an age in which
      brain development and maturation is still very active with cognitive lability. The observed
      responses noted in adults with metastatic cancers involving the CNS and cerebellum treated
      with DM-CHOC-PEN may also occur in medulloblastoma in AYA. Thus, the drug's unique properties
      and lack of toxicities noted in the adult studies merits the Phase I trial proposed here in
      children.

      The specific objectives of this Phase I study were to:

        1. Conduct a Phase II clinical trial with DM-CHOC-PEN in AYA individuals that have advanced
           cancers with central or spinal nervous systems involvements and monitor safety and
           document anticancer activity for the drug. All data was between investigators
           communicated through an e-RAP program. This was accomplished through IND - 68.876.

        2. Verify the pharmacokinetic/dynamic profiles of DM-CHOC-PEN and metabolites in AYA
           subjects with advanced cancers involving the central nervous system.

        3. Analyze data and prepare an Orphan Drug Designated package for FDA submission for AYA
           subjects with CNS involvement from cancer for review.
    

Intervention name(s): DM-CHOC-PEN
Intervention type(s): Drug
Intervention description(s): DM-CHOC-PEN administration by IV infusion
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment