DM-CHOC-PEN Plus Radiation for Brain Tumors
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|ClinicalTrials.gov Identifier: NCT03371004|
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : November 17, 2020
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|
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:
- 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.
- Studying the pharmacokinetic/dynamic profiles of DM-CHOC-PEN and metabolites in adults after being treated with DM-CHOC-PEN and radiation.
- Analyze data and prepare a Phase II clinical trial or a Designation Orphan Drug application for FDA review.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
IV administration as described
Other Name: DM-CHOC-PEN
- 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
- Imaging studies [ Time Frame: 6-weeks after treatments ]MRI Exams of the Brain after Treatments
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
|Contact: Lee R Morgan, MD, PhDfirstname.lastname@example.org|
|Contact: Andrew H Rodgers, PhDemail@example.com|
|United States, Louisiana|
|Tulane University Medical Center||Recruiting|
|New Orleans, Louisiana, United States, 70112|
|Contact: Roy S Weiner, MD 504-988-6061 firstname.lastname@example.org|
|Tulane University Medical School||Recruiting|
|New Orleans, Louisiana, United States, 70112|
|Contact: Marcus L Ware, MD 504-701-4108 email@example.com|
|Contact: Lee R Morgan, MD, PhD 504-583-6135 firstname.lastname@example.org|
|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 email@example.com|
|Contact: Tallat Mahmood, MD 517-913-3890 firstname.lastname@example.org|
|Principal Investigator:||Steven DiBiase, MD||Tulane University Medical Center|
|Principal Investigator:||Lee Roy Morgan, MD, PhD||DEKK-TEC, Inc.|