Advanced CancerPhase 2NCT03668847
DM-CHOC-PEN for Brain Tumors in AYA Subjects
A Phase 2 study testing DM-CHOC-PEN in people with Advanced Cancer and Brain Metastases, run by DEKK-TEC, Inc. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 39 years
- Conditions the study is for
- Advanced Cancer, Brain Metastases
- What is being tested?
- DM-CHOC-PEN
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2019to 30 Sep 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects must have histological proof of a malignancy, which has been treated with standard treatments, which may include radiation, and measurable lesions are not required but must have evidence that the disease is advanced.
- 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.
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- 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.
Who cannot join
- 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 was not permitted.
- Pregnant or lactating females were 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 were 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 were denied enrollment in the study. The possible interactions of these drugs and DM-CHOC-PEN have not been established.
- Coagulopathies - patients requiring full dose anticoagulation with warfarin were excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Tulane University Medical Center
New Orleans, Louisiana, 70112
About this study
Official title: A Phase II: Safety and Tolerance of 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Adolescent and Young Adults (AYA) With Malignancies Involving the CNS
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.
Read the 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:
- 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.
- Verify the pharmacokinetic/dynamic profiles of DM-CHOC-PEN and metabolites in AYA subjects with advanced cancers involving the central nervous system.
- Analyze data and prepare an Orphan Drug Designated package for FDA submission for AYA subjects with CNS involvement from cancer for review.
- Conditions
- Advanced Cancer, Brain Metastases
- Being tested
- DM-CHOC-PEN
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DM-CHOC-PENDrug
DM-CHOC-PEN administration by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| DM-CHOC-PEN | Experimental | 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) - 75 or 98.7 mg/m2 emulsion will be administered IV once every 21-days until relapse Receives: Drug: DM-CHOC-PEN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain Tumor Responses to Therapy
MRI of the brain
Measured: From date of entry into the study until the date of first documented progression or date of of death from any cause, which ever came first, assessed up to 100 months.
Secondary outcomes (1)
Maximum Plasma Concentration [Cmax], Area Under the Curve [AUC]
Blood levels for DM-CHOC-PEN and metabolites will be measured before and after each treatment; HPLC procedures will be involved.
Measured: From initiation of treatment until end of therapy or death from any cause or which ever comes first, assessed up to 8-months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2018
- Study start1 Jan 2019
- Primary completion31 Aug 2021
- Study completion30 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- DEKK-TEC, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ali Baghian, MD, Principal investigator, Tulane University Medical CenterTallat Mahmmod, MD, Principal investigator, Detroit Clinical Research CenterMarcus L Ware, MD, Principal investigator, Ochsner Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03668847
- Sponsor's protocol ID
- DTI-026
- Status last verified
- Nov 2022
- First submitted
- 5 Sep 2018
- Last updated
- 8 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data regarding subject enrollment will be coded and electronically submitted to DEKK-TEC for submission to the FDA. Other trial sites are being evaluated. After all are chosen a decision will be made.
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II: Safety and Tolerance of 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Adolescent and Young Adults (AYA) With Malignancies Involving the CNS
- ClinicalTrials.gov ID
- NCT03668847
- Acronym / sponsor ID
- DTI-026
- Conditions
- Advanced Cancer, Brain Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- DEKK-TEC, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 13 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Verify the pharmacokinetic/dynamic profiles of DM-CHOC-PEN and metabolites in AYA subjects with advanced cancers involving the central nervous system.
- Analyze data and prepare an Orphan Drug Designated package for FDA submission for AYA subjects with CNS involvement from cancer for review.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DM-CHOC-PEN | Experimental | Drug: DM-CHOC-PEN4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) - 75 or 98.7 mg/m2 emulsion will be administered IV once every 21-days until relapse |
Who may qualify
- Ages
- 15 to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Subjects must have histological proof of a malignancy, which has been treated with standard treatments, which may include radiation, and measurable lesions are not required but must have evidence that the disease is advanced.
- 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.
Key exclusion criteria (6 listed)
- 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 was not permitted.
- Pregnant or lactating females were 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 were 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 were denied enrollment in the study. The possible interactions of these drugs and DM-CHOC-PEN have not been established.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DM-CHOC-PENDM-CHOC-PEN administration by IV infusion | Drug | DM-CHOC-PEN |
Primary outcome
Brain Tumor Responses to Therapy
Time frame: From date of entry into the study until the date of first documented progression or date of of death from any cause, which ever came first, assessed up to 100 months.
MRI of the brain
1 secondary outcome
Maximum Plasma Concentration [Cmax], Area Under the Curve [AUC]
Time frame: From initiation of treatment until end of therapy or death from any cause or which ever comes first, assessed up to 8-months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Individual participant dataSharing planned: Yes. All data regarding subject enrollment will be coded and electronically submitted to DEKK-TEC for submission to the FDA. Other trial sites are being evaluated. After all are chosen a decision will be made.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ali Baghian, MD principal investigator
Tulane University Medical Center
Tallat Mahmmod, MD principal investigator
Detroit Clinical Research Center
Marcus L Ware, MD principal investigator
Ochsner Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DM-CHOC-PEN in people with Advanced Cancer and Brain Metastases, run by DEKK-TEC, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain Tumor Responses to Therapy (time frame: From date of entry into the study until the date of first documented progression or date of of death from any cause, which ever came first, assessed up to 100 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.