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DM-CHOC-PEN Plus Radiation for Brain Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03371004
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : July 28, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
DEKK-TEC, Inc.

Brief 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) (1). DM-CHOC-PEN has completed Phase I/II trials in humans with primary and secondary tumors involving the brain with success. Complete remissions in both primary astrocytoma and metastatic lung and leukemia malignancies.

This trial is open for adult subjects with advanced cancer - brain involvement is required.


Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine Phase 1

Detailed Description:

The primary goal of this Phase I oncology clinical trial will be to evaluate the safety and use of 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) plus radiation, as anticancer therapy for adults with advanced cancer involving the central nervous system (CNS) involvement.

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 adult Phase I/II clinical trials - IND - 68,876.

The drug recently received Orphan Drug designation for NSCLC involving the brain.

The FDA supports the proposed Phase I clinical trial designed to identify safety, toxicities and an acceptable MTD of the drug in combination with radiation in adult cancers subjects with CNS involvement.

Almost 700,000 people in the US are living with tumors involving the CNS or spinal nervous system (SNS) tumors. Trends in CNS tumors have sharply increased since 1989 for individuals with a history of cancer, who appeared to have 'beaten the odds', only to have a reoccurrence from cancer involving the CNS after years of remission; the most common types of cancer in AYA individuals are - from lung, breast, melanoma, and sarcoma malignancies. This group of individuals deserves special attention.

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 neurotoxic behavioral alterations and associated events supports the drug's use in combination with radiation in the treatment of CNS tumors. The observed responses noted in adults with metastatic cancers involving the CNS and cerebellum treated with DM-CHOC-PEN is encouraging. Thus, the drug's unique properties and lack of toxicities noted in the adult studies merits the Phase I trial proposed here in combination with radiation.

The specific objectives of this Phase I study will be to:

  1. Conduct a Phase I clinical trial with DM-CHOC-PEN plus radiation in adults with advanced cancers involving the central nervous system to document toxicities, define an acceptable maximum tolerated dose (MTD), and identify anticancer activity for the binary treatment DM-CHOC-PEN plus radiation. All data will be communicated through an e-RAP program. This will be accomplished through IND - 68.876.
  2. Studying the pharmacokinetic/dynamic profiles of DM-CHOC-PEN and metabolites in adults after being treated with DM-CHOC-PEN and radiation.
  3. Analyze data and prepare a Phase II clinical trial or a Designation Orphan Drug application for FDA review.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial to Evaluate Safety and Tolerance of Intravenous 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Adult Subjects With Cancer Involving the CNS
Actual Study Start Date : February 5, 2016
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Arm Intervention/treatment
Experimental: DM-CHOC-PEN + Radiation
4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) - 39-89.7 MG/M2 iv once and then 3-weeks later radiation - 15-30 Gy will be administered
Drug: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine
IV administration as described
Other Name: DM-CHOC-PEN




Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1 year ]
    Laboratory and imaging studies to verify responses


Secondary Outcome Measures :
  1. Imaging studies [ Time Frame: 6-weeks after treatments ]
    MRI Exams of the Brain after Treatments



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:: Inclusion Criteria will be as follows -

  • Subjects must have histological proof of a CNS malignancy (primary or metastatic), which has been treated with standard treatments, that may include radiation, and must have measurable lesions.
  • Subjects must have life expectancy of at least 12 weeks and a Karnofsky performance score: > 60 % (or a Zubrod performance status of < 2).
  • The age limit - a limit of 39 years of age. Gender is not a criterion.
  • 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); no nitrosourea type drug or ipilumimab treatments are permitted within the last six (6) weeks prior to enrollment. No major surgery within 14 days of enrollment. Subjects may continue to receive anti- estrogen/steroid therapy that has been initiated at least eight weeks prior to enrollment in the study.
  • Subjects should have adequate bone marrow function defined as a peripheral WBC >3,000/mm3 with an ANC >1500/mm3 and a platelet count >100,000/mm3.
  • Subjects should have hepatic function (alkaline phosphatase, AST and ALT) < ULN and renal functions with serum creatinine - <1.5 x UNL. If a patient has liver metastasis and/or a history of liver disease - they will receive a lower dose of the drug per treatment protocol.
  • Subjects should not be allergic to eggs or soy beans.
  • 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. Subjects with a history of cardiac disease must be stable.
  • Subjects and/or legal guardian 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 Human Investigation Review Committee.

Exclusion Criteria:Criteria: Inclusion Criteria: Inclusion Criteria will be as follows -

  • Subjects must have histological proof of a CNS malignancy (primary or metastatic), which has been treated with standard treatments, that may include radiation, and must have measurable lesions.
  • Subjects must have life expectancy of at least 12 weeks and a Karnofsky performance score: > 60 % (or a Zubrod performance status of < 2).
  • The age limit - a limit of 39 years of age. Gender is not a criterion.
  • 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); no nitrosourea type drug or ipilumimab treatments are permitted within the last six (6) weeks prior to enrollment. No major surgery within 14 days of enrollment. Subjects may continue to receive anti- estrogen/steroid therapy that has been initiated at least eight weeks prior to enrollment in the study.
  • Subjects should have adequate bone marrow function defined as a peripheral WBC >3,000/mm3 with an ANC >1500/mm3 and a platelet count >100,000/mm3.
  • Subjects should have hepatic function (alkaline phosphatase, AST and ALT) < ULN and renal functions with serum creatinine - <1.5 x UNL. If a patient has liver metastasis and/or a history of liver disease - they will receive a lower dose of the drug per treatment protocol.
  • Subjects should not be allergic to eggs or soy beans.
  • 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. Subjects with a history of cardiac disease must be stable.
  • Subjects and/or legal guardian 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 Human Investigation Review Committee.

Exclusion Criteria: Exclusion criteria will be as follows:

  • Subjects with concurrent severe and/or uncontrolled medical co-morbidities - including active infections, unstable uncontrolled diabetes, cardiovascular and pulmonary, renal, 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. Males who are having sexual relations with women capable of child bearing must use the barrier birth control while on the study and for 3-months after the last dose of the study drug.
  • Subjects taking CYP3A4 inducers or inhibitors are not eligible since it is not known whether the study drug is metabolized through this pathway. The following CYP3A4 inhibitors/inducers are not permitted during the trial - phenobarbital, fluconazole, erythromycin, verapamil; the latter 3-drugs are moderate CYP3A4 inhibitors.
  • Subjects taking the following medications may experience QT/QTc interval prolongation and are not eligible for the trial - most anti-arrhythmia drugs (incl. amiodarone), erythromycin, quinolone antibiotics, ketoconazole, Zithromax, and phenothiazine and will be denied enrollment in the study. The possible interactions of these drugs and DM-CHOC-PEN have not been established. Subjects receiving these drugs will only be eligible if they discontinue the drugs and have an acceptable ECG.
  • Coagulopathies - patients requiring full dose anticoagulation with warfarin are excluded. However, patients stable and on other anticoagulants can be incl

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03371004


Contacts
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Contact: Lee R Morgan, MD, PhD 5045836135 lrm1579@aol.com
Contact: Andrew H Rodgers, PhD 5045836135 ahrodgers@gmail.com

Locations
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United States, Louisiana
Tulane University Medical Center Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Roy S Weiner, MD    504-988-6061    rweiner@tulane.edu   
Tulane University Medical School Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Marcus L Ware, MD    504-701-4108    marcusware@gmail.com   
Contact: Lee R Morgan, MD, PhD    504-583-6135    lrm1579@aol.com   
Principal Investigator: Marcus L Ware, MD         
United States, Michigan
Detroit Clinical Research Centers Recruiting
Detroit, Michigan, United States, 48336
Contact: Craig Gorgon, DO    248-522-0222    craig.gordon@dcrc.us   
Contact: Tallat Mahmood, MD    517-913-3890    tallat_m@yahoo.com   
Sponsors and Collaborators
DEKK-TEC, Inc.
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Steven DiBiase, MD Tulane University Medical Center
Principal Investigator: Lee Roy Morgan, MD, PhD DEKK-TEC, Inc.
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Responsible Party: DEKK-TEC, Inc.
ClinicalTrials.gov Identifier: NCT03371004    
Other Study ID Numbers: DTI-025
5R43CA213545-02 ( U.S. NIH Grant/Contract )
R43CA213545 ( U.S. NIH Grant/Contract )
IND 68876 ( Registry Identifier: DM-CHOC-PEN )
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: July 28, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Other trial centers are being evaluated
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Upon release of the Clinical Trials.gov approval
URL: http://dekk-tec.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by DEKK-TEC, Inc.:
DM-CHOC-PEN
Radiation
Cancer