Primary Brain TumorsPhase 2DM-CHOC-PENNCT02038218
Study of 4-Demethyl-4-cholesteryloxycarbonylpenclome (DM-CHOC-PEN) in Patients With Brain Tumors
A Phase 2 study testing 4-Demethyl-4-cholestryloxycarbonylpenclomedine in people with Primary Brain Tumors and Metastatic Malignant Neoplasm to Brain, run by DEKK-TEC, Inc. at 3 sites in United States.
Trial summary
DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate that has demonstrated antineoplastic activities in patients with advanced cancers - melanoma, lung, breast and glioblastoma multiforme (GBM) involving the CNS during a Phase I study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Brain Tumors, Metastatic Malignant Neoplasm to Brain
- What is being tested?
- 4-Demethyl-4-cholestryloxycarbonylpenclomedine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2013to Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histological proof of a cancer - melanoma, breast, or lung cancer - which has spread to the CNS or glioblastoma (GBM) or other primary malignant neoplasm of the CNS which has been treated with standard treatments, which may include radiation, and must be measurable (RECIST).
- Patients 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 - 18 or older. Gender is not a criterion.
- All patients 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. Patients may continue to receive anti-estrogen/steroid therapy that has been initiated at least eight weeks prior to enrollment in the study.
- Patients 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.
- Patients 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.
- Patients should not be allergic to eggs or soy beans. Patients 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.
- Patients 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. Patients must have CNS involvement - from a malignancy. Lung cancer may be either small cell or non-small cell.
Who cannot join
- Patients 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.
- Patients 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 - the azole antifungal - fluconazole, erythromycin, phenobarbital, verapamil.
- Patients 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. Patients receiving these drug 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 included.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The University of Texas Health Science Center
Houston, Texas, 77030
Detroit Clinical Research Centers
Lansing, Michigan, 48336
Tulane University Medical Center
New Orleans, Louisiana, 70112
About this study
Official title: A Phase II Trial: Safety and Tolerance of Intravenous 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Malignancies Involving the Central Nervous System
DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate that has demonstrated antineoplastic activities in patients with advanced cancers - melanoma, lung, breast and glioblastoma multiforme (GBM) involving the CNS during a Phase I study. These findings support the preclinical responses seen in mice bearing intracerebrally implanted human breast and GBM tumor xenografts. Toxicity was acceptable - hyperbilirubinemia (in patients with liver disease and/or liver metastasis). No hematological, renal, cardiovascular, behavioral or cognitive impairment/neurotoxicities were noted during the Phase I human trial or in previous pre-clinical studies.
The drug is available for use as a soy bean oil/egg yolk lecithin/glycerin water emulsion; the latter continues to be chemically and biologically stable and safe.
Read more
Patients with advanced lung, breast and melanoma cancers spread to the CNS and primary CNS malignancies will be eligible for enrollment and treatment, providing the required blood and other eligibility requirements are met. The trial will be 2-tiered - patients with liver involvement vs. non-liver involvement will be treated with different doses of the drug.
The trial is open and patients are currently being enrolled and treated with the protocol.
Read the detailed description
DM-CHOC-PEN has been selected for Phase II intravenous studies in the treatment of patients with advanced malignancies with central nervous system measurable disease based on the improved PFS and objective responses seen for patients treated during the Phase I DTI-021 trial and the manageable toxicities noted. Melanoma, breast and lung cancers involving the CNS have responded to DM-CHOC-PEN in the Phase I study, thus the basis for the choice of tumors to be treated in the Phase II trial. Currently, the opinion is that the drug is penetrating the blood brain barrier (BBB) attached to rbcs and released intracerebrally in tumor masses in situ.
The trial will be carefully monitored, and if a cancer type has >3 confirmed responders in the first 18 evaluable patients (Stage -1 enrollment); accrual will be expanded for that tumor type with a goal of 7/43 for achieving an 80% power at the 5% level of significance (Stage-2 enrollment) with unacceptable response rate (P0) 0.1 and desirable response rate (P1) 0.25. Thus, each arm will have a 2-stage design. This will allow resources to be directed to the most promising areas - selection of 1 or 2 tumor types to develop via additional trial studies. A desirable response rate is 25% or better. The above is for each tumor type - lung, breast, melanoma and GBM.
In summary, for any tumor type or treatment sub-group, a response rate of <15% or a rate of "possibly treatment-related Gr-3/4 toxicities" of >25% will be considered unacceptable and enrollment in the respective tumor type category will be discontinued.
- Being tested
- 4-Demethyl-4-cholestryloxycarbonylpenclomedine
- Keywords
- DM-CHOC-PEN, CNS, brain, melanoma, lung cancer, breast cancer, glioblastoma multiforme, primary brain tumors
- Medical subject headings
- Brain Neoplasms, Melanoma, Lung Neoplasms, Breast Neoplasms, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4-Demethyl-4-cholestryloxycarbonylpenclomedineDrug
Also called DM-CHOC-PEN
This will be an open-label, uncontrolled two-arm, multi-center study in patients with CNS involvement from melanoma, breast, lung cancers or primary malignancies of the CNS. Patients can be previously treated with radiation and systemic therapies and are eligible if they also have other sites of cancer involvement.
Two Cohorts of patients will be treated every 21 days with a single infusion of DM-CHOC-PEN as an out-patient:
Cohort 1: Patients with liver involvement or history of disease will be treated at a dose of 85.8 mg/m2 and;
Cohort 2: Patients without liver involvement or history of liver disease, will be treated at a dose of 98.7 mg/m2.
Patients in both cohorts will discontinue dosing with DM-CHOC-PEN when there are any unacceptable toxicities, progression of cancer or patient compliance.
| Study group | Role | What they receive |
|---|---|---|
| DM-CHOC-PEN | Experimental | Two Cohorts of patients will be treated every once every 21 days with a single infusion of DM-CHOC-PEN as an out-patient. Patients will be divided into:
Cohort 1: Patients with liver involvement or history of disease will be treated at a dose of 85.8 mg/m2 and;
Cohort 2: Patients without liver involvement or history of liver disease, will be treated at a dose of 98.7 mg/m2.
Patients in both cohorts will discontinue dosing with DM-CHOC-PEN when there are any unacceptable toxicities, progression of cancer or patient compliance. Receives: Drug: 4-Demethyl-4-cholestryloxycarbonylpenclomedine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Diameter
Tumor Diameter from patient scans
Measured: Until remission or off treatment due to progression
Overall Survival
Overall survival in months
Measured: Until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2014 (estimated)
- Study startSep 2013
- Primary completionMay 2016
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Brain TumorsStudies 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- DEKK-TEC, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Tulane University, Icahn School of Medicine at Mount Sinai, Detroit Clinical Research Center, National Cancer Institute (NCI), Ochsner Health System, The University of Texas Health Science Center, Houston
- Responsible party
- Sponsor
- Investigators
- Lee R Morgan, MD, PhD, Study director, DEKK-TEC, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02038218
- Sponsor's protocol ID
- DTI-022
- Other IDs
- R44CA125871-03
- Acronym
- DM-CHOC-PEN
- Status last verified
- Sep 2020
- First submitted
- 15 Jan 2014
- Last updated
- 16 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: As approved by the NCI
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial: Safety and Tolerance of Intravenous 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Malignancies Involving the Central Nervous System
- ClinicalTrials.gov ID
- NCT02038218
- Acronym / sponsor ID
- DM-CHOC-PEN / DTI-022
- Keywords
- DM-CHOC-PEN, CNS, brain, melanoma, lung cancer, breast cancer, glioblastoma multiforme, primary brain tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- DEKK-TEC, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Tulane University, Icahn School of Medicine at Mount Sinai, Detroit Clinical Research Center, National Cancer Institute (NCI), Ochsner Health System, The University of Texas Health Science Center, Houston
- Study start
- Sep 2013
- Primary completion
- May 2016 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 16 Jan 2014 (estimated)
- Results
- Posted 16 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate that has demonstrated antineoplastic activities in patients with advanced cancers - melanoma, lung, breast and glioblastoma multiforme (GBM) involving the CNS during a Phase I study. These findings support the preclinical responses seen in mice bearing intracerebrally implanted human breast and GBM tumor xenografts. Toxicity was acceptable - hyperbilirubinemia (in patients with liver disease and/or liver metastasis). No hematological, renal, cardiovascular, behavioral or cognitive impairment/neurotoxicities were noted during the Phase I human trial or in previous pre-clinical studies.
The drug is available for use as a soy bean oil/egg yolk lecithin/glycerin water emulsion; the latter continues to be chemically and biologically stable and safe.
Patients with advanced lung, breast and melanoma cancers spread to the CNS and primary CNS malignancies will be eligible for enrollment and treatment, providing the required blood and other eligibility requirements are met. The trial will be 2-tiered - patients with liver involvement vs. non-liver involvement will be treated with different doses of the drug.
The trial is open and patients are currently being enrolled and treated with the protocol.
Detailed description
DM-CHOC-PEN has been selected for Phase II intravenous studies in the treatment of patients with advanced malignancies with central nervous system measurable disease based on the improved PFS and objective responses seen for patients treated during the Phase I DTI-021 trial and the manageable toxicities noted. Melanoma, breast and lung cancers involving the CNS have responded to DM-CHOC-PEN in the Phase I study, thus the basis for the choice of tumors to be treated in the Phase II trial. Currently, the opinion is that the drug is penetrating the blood brain barrier (BBB) attached to rbcs and released intracerebrally in tumor masses in situ.
The trial will be carefully monitored, and if a cancer type has >3 confirmed responders in the first 18 evaluable patients (Stage -1 enrollment); accrual will be expanded for that tumor type with a goal of 7/43 for achieving an 80% power at the 5% level of significance (Stage-2 enrollment) with unacceptable response rate (P0) 0.1 and desirable response rate (P1) 0.25. Thus, each arm will have a 2-stage design. This will allow resources to be directed to the most promising areas - selection of 1 or 2 tumor types to develop via additional trial studies. A desirable response rate is 25% or better. The above is for each tumor type - lung, breast, melanoma and GBM.
In summary, for any tumor type or treatment sub-group, a response rate of <15% or a rate of "possibly treatment-related Gr-3/4 toxicities" of >25% will be considered unacceptable and enrollment in the respective tumor type category will be discontinued.
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: 4-Demethyl-4-cholestryloxycarbonylpenclomedineTwo Cohorts of patients will be treated every once every 21 days with a single infusion of DM-CHOC-PEN as an out-patient. Patients will be divided into: Cohort 1: Patients with liver involvement or history of disease will be treated at a dose of 85.8 mg/m2 and; Cohort 2: Patients without liver involvement or history of liver disease, will be treated at a dose of 98.7 mg/m2. Patients in both cohorts will discontinue dosing with DM-CHOC-PEN when there are any unacceptable toxicities, progression of cancer or patient compliance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have histological proof of a cancer - melanoma, breast, or lung cancer - which has spread to the CNS or glioblastoma (GBM) or other primary malignant neoplasm of the CNS which has been treated with standard treatments, which may include radiation, and must be measurable (RECIST).
- Patients 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 - 18 or older. Gender is not a criterion.
- All patients 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. Patients may continue to receive anti-estrogen/steroid therapy that has been initiated at least eight weeks prior to enrollment in the study.
- Patients 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)
- Patients 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.
- Patients 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 - the azole antifungal - fluconazole, erythromycin, phenobarbital, verapamil.
- Patients 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. Patients receiving these drug will only be eligible if they discontinue the drugs and have an acceptable ECG.
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 |
|---|---|---|
| 4-Demethyl-4-cholestryloxycarbonylpenclomedineAlso: DM-CHOC-PENThis will be an open-label, uncontrolled two-arm, multi-center study in patients with CNS involvement from melanoma, breast, lung cancers or primary malignancies of the CNS. Patients can be previously treated with radiation and systemic therapies and are eligible if they also have other sites of cancer involvement. Two Cohorts of patients will be treated every 21 days with a single infusion of DM-CHOC-PEN as an out-patient: Cohort 1: Patients with liver involvement or history of disease will be treated at a dose of 85.8 mg/m2 and; Cohort 2: Patients without liver involvement or history of liver disease, will be treated at a dose of 98.7 mg/m2. Patients in both cohorts will discontinue dosing with DM-CHOC-PEN when there are any unacceptable toxicities, progression of cancer or patient compliance. | Drug | DM-CHOC-PEN |
Primary outcome
Tumor Diameter
Time frame: Until remission or off treatment due to progression
Tumor Diameter from patient scans
Overall Survival
Time frame: Until death
Overall survival in months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. As approved by the NCI
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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.
Lee R Morgan, MD, PhD study director
DEKK-TEC, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 4-Demethyl-4-cholestryloxycarbonylpenclomedine in people with Primary Brain Tumors and Metastatic Malignant Neoplasm to Brain, run by DEKK-TEC, Inc. at 3 sites 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 8 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 16 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Yes. Results are posted in the registry (first posted 16 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tumor Diameter (time frame: Until remission or off treatment due to progression). The study lists 2 primary outcomes in all. 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 16 Sep 2020.