GlioblastomaPhase 2NCT03363659
Disulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
A Phase 2 study testing Disulfiram, Copper gluconate and Temozolomide in people with Glioblastoma and Glioblastoma Multiforme, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
One of Disulfiram antitumor effects suggested in preclinical studies is MGMT (methyl-guanine-methyl-transferase) inhibition. Disulfiram MGMT inhibitory effect is enhanced by addition of Copper. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- Disulfiram, Copper gluconate and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2018to 13 Jan 2022
- 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
- Age 18 or older
- Diagnosis of histologically confirmed glioblastoma (WHO grade IV). Subjects with an original histologic diagnosis of low grade glioma or anaplastic glioma (WHO grade II or III) are eligible if a subsequent histological diagnosis of glioblastoma is made
- Patients whose tumor is determined to be unmethylated
- Patients with incomplete resection as determined by residual, measurable gadolinium or contrast-enhancing lesion or lesions
- Recent resection of glioblastoma within 4 weeks of study entry. Patients who have only had a tumor biopsy and who are considered unresectable are eligible (but based on the study accrual this subset of patients with unresectable tumor may be considered for separate analysis)
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤ 2 (see appendix A)
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- Willing to remain abstinent from consuming alcohol while on DSF
- No prior radiation or chemotherapy
- Meets the following laboratory criteria:
- Absolute neutrophil count ≥ 1,500/mcL (microliter)
- Platelets ≥ 100,000/mcL
- Hemoglobin > 10.0 g/dL (grams/deciliter) (transfusion and/or ESA (erythropoiesis-stimulating agent) allowed)
- Total bilirubin and alkaline phosphatase ≤ 2x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN
- Blood urea nitrogen (BUN) and creatinine < 1.5 x ULN
- Able to take oral medication
- Able to understand and willing to sign an institutional review board (IRB)-approved written informed consent document (legally authorized representative permitted)
Who cannot join
- Radiographic evidence of leptomeningeal dissemination, extensive intraparenchymal dissemination, infratentorial tumor, or metastatic disease to sites remote from the supratentorial brain
- Enrolled in another clinical trial testing a novel therapy or drug
- Received prior radiation therapy or chemotherapy for glioblastoma
- History of allergic reaction/hypersensitivity to DSF (without alcohol) or copper.
- Treatment with the following medications that may interfere with metabolism of DSF: warfarin (unless otherwise chosen by the study PI who will actively adjust Coumadin dose to consistently maintain a safe, therapeutic international normalized ratio (INR) < 3, theophylline, amitriptyline, isoniazid, metronidazole, phenytoin, phenobarbital, chlorzoxazone, halothane, imipramine, chlordiazepoxide, diazepam. (Note: lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with DSF).
- Active severe hepatic or renal disease
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- Grade 2 or higher peripheral neuropathy or ataxia per NCI CTCAE version 4.0 (2009)
- History of idiopathic seizure disorder schizophrenia, or psychosis unrelated to glioblastoma, corticosteroid, or anti-epileptic medications
- History of Wilson's or Gilbert's disease
- Current excessive use of alcohol
Trial locations and contacts
1 site in 1 country.
United States1 site
Aurora Health Care, Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, 53215
About this study
Official title: A Phase II, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients With Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme
One of Disulfiram antitumor effects suggested in preclinical studies is MGMT (methyl-guanine-methyl-transferase) inhibition. Disulfiram MGMT inhibitory effect is enhanced by addition of Copper. This study evaluates the impact of Disulfiram (DSF) + Copper (Cu) combination when added to standard Temozolomide in the treatment of unmethylated Glioblastoma Multiforme (GBM) patients.
Read the detailed description
Glioblastoma is the most common malignant primary brain tumor and one of the most devastating cancers. The current standard of care for glioblastoma includes maximal safe resection followed by radiotherapy and temozolomide, which results in a median progression-free survival of less than 7 months, and median overall survival (OS) of less than 15 months. Moreover, patients with unmethylated glioblastoma respond poorly to this current standard treatment. This clinical trial evaluates the potential role of continuous, upfront use of Disulfiram in combination with Copper gluconate in enhancing temozolomide effect in the treatment of unmethylated Glioblastoma multiforme (GBM) patients.
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Being tested
- Disulfiram, Copper gluconate, Temozolomide
- Keywords
- Glioblastoma, Glioblastoma Multiforme, Anaplastic Glioma, Unmethylated
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
Also called Antabuse
Disulfiram is taken orally, twice daily.
Copper gluconateDietary supplement
Copper gluconate is taken orally, twice daily
TemozolomideDrug
Also called Temodar, Temodal, Temcad
Temozolomide is taken once daily
| Study group | Role | What they receive |
|---|---|---|
| DSF-Cu with temozolomide and radiation | Experimental | Disulfiram (DSF; oral) / copper gluconate (Cu; oral) dosed at 125 mg / 2 mg, twice daily. Temozolomide will be administered following the standard Stupp protocol at a dose of 75 mg/m2 for 42 days with concurrent radiation therapy. Temozolomide maintenance dose will be 150 mg/m2 once daily on Days 1-5 of every 28-day cycle while DSF-Cu is continued twice daily, as tolerated, for the duration of the Temozolomide adjuvant treatment. Patients demonstrating continued benefit from the adjuvant temozolomide after 6 cycles can continue treatment to a maximum of 12 cycles Receives: Drug: Disulfiram; Dietary Supplement: Copper gluconate; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 Months Progression Free Survival (PFS)
To determine 6 month PFS of patients with unmethylated glioblastoma treated with DSF-Cu in combination with concurrent radiation and temozolomide. This was assessed by the number of participants who did not have disease progression and were alive at 6 months.
Measured: 6 months
Overall Survival
Overall Survival will be assessed as a number of participants alive at 1 and 2 years.
Measured: 1 and 2 years
Secondary outcomes (1)
Quality of Life (QOL)
Edmonton Symptom Assessment System - Revised (ESAS-r) questionnaire
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2017
- Study start28 Mar 2018
- Primary completion13 Jan 2022
- Study completion13 Jan 2022
Why it stopped: Investigator decision
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 GlioblastomaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- 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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Asadullah Khan, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03363659
- Sponsor's protocol ID
- 17.56
- Status last verified
- Jan 2023
- First submitted
- 30 Nov 2017
- Last updated
- 3 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Disulfiram and Copper Gluconate When Added to Standard Temozolomide Treatment in Patients With Newly Diagnosed Resected Unmethylated Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT03363659
- Acronym / sponsor ID
- 17.56
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Keywords
- Glioblastoma, Glioblastoma Multiforme, Anaplastic Glioma, Unmethylated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigator decision
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 28 Mar 2018 (actual)
- Primary completion
- 13 Jan 2022 (actual)
- Study completion
- 13 Jan 2022 (actual)
- First posted
- 6 Dec 2017 (actual)
- Results
- Posted 8 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One of Disulfiram antitumor effects suggested in preclinical studies is MGMT (methyl-guanine-methyl-transferase) inhibition. Disulfiram MGMT inhibitory effect is enhanced by addition of Copper. This study evaluates the impact of Disulfiram (DSF) + Copper (Cu) combination when added to standard Temozolomide in the treatment of unmethylated Glioblastoma Multiforme (GBM) patients.
Detailed description
Glioblastoma is the most common malignant primary brain tumor and one of the most devastating cancers. The current standard of care for glioblastoma includes maximal safe resection followed by radiotherapy and temozolomide, which results in a median progression-free survival of less than 7 months, and median overall survival (OS) of less than 15 months. Moreover, patients with unmethylated glioblastoma respond poorly to this current standard treatment. This clinical trial evaluates the potential role of continuous, upfront use of Disulfiram in combination with Copper gluconate in enhancing temozolomide effect in the treatment of unmethylated Glioblastoma multiforme (GBM) patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DSF-Cu with temozolomide and radiation | Experimental | Drug: Disulfiram, Dietary Supplement: Copper gluconate, Drug: TemozolomideDisulfiram (DSF; oral) / copper gluconate (Cu; oral) dosed at 125 mg / 2 mg, twice daily. Temozolomide will be administered following the standard Stupp protocol at a dose of 75 mg/m2 for 42 days with concurrent radiation therapy. Temozolomide maintenance dose will be 150 mg/m2 once daily on Days 1-5 of every 28-day cycle while DSF-Cu is continued twice daily, as tolerated, for the duration of the Temozolomide adjuvant treatment. Patients demonstrating continued benefit from the adjuvant temozolomide after 6 cycles can continue treatment to a maximum of 12 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age 18 or older
- Diagnosis of histologically confirmed glioblastoma (WHO grade IV). Subjects with an original histologic diagnosis of low grade glioma or anaplastic glioma (WHO grade II or III) are eligible if a subsequent histological diagnosis of glioblastoma is made
- Patients whose tumor is determined to be unmethylated
- Patients with incomplete resection as determined by residual, measurable gadolinium or contrast-enhancing lesion or lesions
- Recent resection of glioblastoma within 4 weeks of study entry. Patients who have only had a tumor biopsy and who are considered unresectable are eligible (but based on the study accrual this subset of patients with unresectable tumor may be considered for separate analysis)
Key exclusion criteria (10 listed)
- Radiographic evidence of leptomeningeal dissemination, extensive intraparenchymal dissemination, infratentorial tumor, or metastatic disease to sites remote from the supratentorial brain
- Enrolled in another clinical trial testing a novel therapy or drug
- Received prior radiation therapy or chemotherapy for glioblastoma
- History of allergic reaction/hypersensitivity to DSF (without alcohol) or copper.
- Treatment with the following medications that may interfere with metabolism of DSF: warfarin (unless otherwise chosen by the study PI who will actively adjust Coumadin dose to consistently maintain a safe, therapeutic international normalized ratio (INR) < 3, theophylline, amitriptyline, isoniazid, metronidazole, phenytoin, phenobarbital, chlorzoxazone, halothane, imipramine, chlordiazepoxide, diazepam. (Note: lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with DSF).
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 |
|---|---|---|
| DisulfiramAlso: AntabuseDisulfiram is taken orally, twice daily. | Drug | DSF-Cu with temozolomide and radiation |
| Copper gluconateCopper gluconate is taken orally, twice daily | Dietary supplement | DSF-Cu with temozolomide and radiation |
| TemozolomideAlso: Temodar, Temodal, TemcadTemozolomide is taken once daily | Drug | DSF-Cu with temozolomide and radiation |
Primary outcome
6 Months Progression Free Survival (PFS)
Time frame: 6 months
To determine 6 month PFS of patients with unmethylated glioblastoma treated with DSF-Cu in combination with concurrent radiation and temozolomide. This was assessed by the number of participants who did not have disease progression and were alive at 6 months.
Overall Survival
Time frame: 1 and 2 years
Overall Survival will be assessed as a number of participants alive at 1 and 2 years.
1 secondary outcome
Quality of Life (QOL)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Asadullah Khan, MD principal investigator
Wake Forest University Health Sciences
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 Disulfiram, Copper gluconate and Temozolomide in people with Glioblastoma and Glioblastoma Multiforme, run by Wake Forest University Health Sciences 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 17 inclusion and 10 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: stopped early, as of the sponsor's last update on 3 Oct 2024. 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?
Yes. Results are posted in the registry (first posted 8 Sep 2023). 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?
6 Months Progression Free Survival (PFS) (time frame: 6 months). 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 3 Oct 2024.