Glioblastoma MultiformePhase 2GLIODISNCT01777919
Disulfiram/Copper Combination In The Treatment of Newly Diagnosed Glioblastoma Multiform
A Phase 2 study testing Temozolomide, Disulfiram and Copper in people with Glioblastoma Multiforme, run by Olympion Medical Center at 1 site in Greece.
Trial summary
Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Temozolomide, Disulfiram and Copper
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteGreece
- Study dates
- Jan 2027to Jan 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Histopathologically confirmed diagnosis of glioblastoma (World Health Organization [WHO] grade IV astrocytoma). Patients must be newly diagnosed with unifocal supratentorial GBM amenable to gross total resection (< 1 cm. enhancing rim) and not yet received chemoradiation.
- Patient must have undergone a gross total surgical resection of the tumor mass with post-surgical MRI (performed within 72 hours after operation) demonstration of adequacy defined as < 1.0 cm of residual enhancement away from resection cavity perimeter.
- Ability to start disulfiram on the 5th postoperative day
- ≥ 18 years of age
- Karnofsky Performance Status (KPS) ≥ 70%
- Adequate bone marrow function, defined as:
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- Absolute neutrophil count ≥ 1000 cells/mm3 Hemoglobin ≥ 10 g/dL Platelet count ≥ 100,000 cells/mm3
- Adequate hepatic function, defined as:
- Bilirubin ≤ 2.0 mg/dL Alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 4x upper limit of normal (ULN)
- Adequate renal function, defined blood urea nitrogen (BUN) < 30 mg/dL and creatinine < 2 mg/dL
- Prothrombin time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6x control unless therapeutically warranted
- Female patients of child-bearing potential must have negative serum or urine pregnancy test
- If not surgically sterile, male and female patients of childbearing age must use double barrier contraception (hormonal; intrauterine device; barrier)
- Patient must give written informed consent prior to any study-specific procedures being implemented.
Who cannot join
- Recurrent disease
- Infratentorial or multifocal tumor.
- Placement of Gliadel wafer
- No severe, active comorbidity, including any of the following:
- Unstable angina and/or congestive heart failure requiring hospitalization
- Transmural myocardial infarction within the last 6 months
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- Chronic obstructive pulmonary disease
- Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS) related illness or other serious medical illness
- Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy
- Known history of an autoimmune disorder
- Presence of any other active malignancy or prior history of malignancy (except for basal cell carcinoma of the skin)
- Alcoholism
- Breastfeeding
- Prior or planned chemotherapy, immunotherapy, biologic therapy, radiation therapy, radioimmunotherapy, hormonal therapy, or experimental therapy for brain tumor
- History of severe allergic reaction to contrast media.
- Inability to undergo an MRI.
- Patients treated on any other therapeutic clinical trial within 30 days prior to study entry or during participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Greece1 site
Olympion Medical Center
Pátrai, 26443
Petros N Karamanakos, MD, PhD
Petros N Karamanakos, MD, PhD
About this study
Official title: A PHASE II CLINICAL TRIAL FOR THE EVALUATION OF THE EFFICACY OF DISULFIRAM/COPPER COMBINATION AS AN ADJUVANT AND CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORM
Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence.
GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme.
Read more
Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by ~100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent.
In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Temozolomide, Disulfiram, Copper
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodar
already included
DisulfiramDrug
Also called Antabuse
already included
CopperDrug
already included
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide+Disulfiram/copper | Experimental | Disulfiram/copper combination will be started on the 5th postoperative day and before the initiation of the standard radiochemotherapy (fractionated irradiation with a total dose of 60 Gy with concomitant 75 mg/m2 body surface temozolomide each day, including weekends, during irradiation). After completion of the radiation therapy patients will receive maintenance temozolomide 150-200 mg/m2 body surface on Days 1-5 every 28 days for 6 months. Daily administration of disulfiram and copper will take place for the whole study period.
NOTE: Patients may receive additional maintenance temozolomide at the discretion of the treating medical oncologist. Receives: Drug: Temozolomide; Drug: Disulfiram; Drug: Copper |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Measured: 6 months
Secondary outcomes (1)
Overall survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study startJan 2027 (estimated)
- Primary completionJan 2029 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies 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
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Olympion Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ioannina, University of Eastern Finland, University of Ulm
- Responsible party
- Principal investigator, Petros Karamanakos, MD, PhD, Olympion Medical Center
- Investigators
- Petros N Karamanakos, MD, PhD, Principal investigator, Department of Neurosurgery, Olympion Medical Center, 26443, Patras, GREECE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01777919
- Sponsor's protocol ID
- PK-18081973
- Acronym
- GLIODIS
- Status last verified
- May 2025
- First submitted
- 24 Jan 2013
- Last updated
- 25 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Karamanakos PN. Possible role for furazolidone in the treatment of glioblastoma multiforme. J BUON. 2013 Oct-Dec;18(4):1097. No abstract available.
PubMed 24344045
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE II CLINICAL TRIAL FOR THE EVALUATION OF THE EFFICACY OF DISULFIRAM/COPPER COMBINATION AS AN ADJUVANT AND CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORM
- ClinicalTrials.gov ID
- NCT01777919
- Acronym / sponsor ID
- GLIODIS / PK-18081973
- Conditions
- Glioblastoma Multiforme
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Olympion Medical CenterUniversity, hospital or other
- Collaborators
- University of Ioannina, University of Eastern Finland, University of Ulm
- Study start
- Jan 2027 (estimated)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 29 Jan 2013 (estimated)
- 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.
Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence.
GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme.
Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by ~100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent.
In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temozolomide+Disulfiram/copper | Experimental | Drug: Temozolomide, Drug: Disulfiram, Drug: CopperDisulfiram/copper combination will be started on the 5th postoperative day and before the initiation of the standard radiochemotherapy (fractionated irradiation with a total dose of 60 Gy with concomitant 75 mg/m2 body surface temozolomide each day, including weekends, during irradiation). After completion of the radiation therapy patients will receive maintenance temozolomide 150-200 mg/m2 body surface on Days 1-5 every 28 days for 6 months. Daily administration of disulfiram and copper will take place for the whole study period. NOTE: Patients may receive additional maintenance temozolomide at the discretion of the treating medical oncologist. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histopathologically confirmed diagnosis of glioblastoma (World Health Organization [WHO] grade IV astrocytoma). Patients must be newly diagnosed with unifocal supratentorial GBM amenable to gross total resection (< 1 cm. enhancing rim) and not yet received chemoradiation.
- Patient must have undergone a gross total surgical resection of the tumor mass with post-surgical MRI (performed within 72 hours after operation) demonstration of adequacy defined as < 1.0 cm of residual enhancement away from resection cavity perimeter.
- Ability to start disulfiram on the 5th postoperative day
- ≥ 18 years of age
- Karnofsky Performance Status (KPS) ≥ 70%
Key exclusion criteria (18 listed)
- Recurrent disease
- Infratentorial or multifocal tumor.
- Placement of Gliadel wafer
- No severe, active comorbidity, including any of the following:
- Alcoholism
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 |
|---|---|---|
| TemozolomideAlso: Temodaralready included | Drug | Temozolomide+Disulfiram/copper |
| DisulfiramAlso: Antabusealready included | Drug | Temozolomide+Disulfiram/copper |
| Copperalready included | Drug | Temozolomide+Disulfiram/copper |
Primary outcome
Progression-free survival
Time frame: 6 months
1 secondary outcome
Overall survival
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Derived from this study: PubMed 24344045Karamanakos PN. Possible role for furazolidone in the treatment of glioblastoma multiforme. J BUON. 2013 Oct-Dec;18(4):1097. No abstract available.
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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.
Petros N Karamanakos, MD, PhD principal investigator
Department of Neurosurgery, Olympion Medical Center, 26443, Patras, GREECE
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 Temozolomide, Disulfiram and Copper in people with Glioblastoma Multiforme, run by Olympion Medical Center at 1 site in Greece.
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 14 inclusion and 18 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: opening soon, as of the sponsor's last update on 25 May 2025. 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 Greece. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Petros N Karamanakos, MD, PhD (+30 6945 548463, pkaramanakos@olympion-sa.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01777919, which also lists 1 linked publication.
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 25 May 2025.