GlioblastomaEarly Phase 1NCT01907165
Disulfiram in Treating Patients With Glioblastoma Multiforme After Radiation Therapy With Temozolomide
A Early Phase 1 study testing Temozolomide, Disulfiram and Copper gluconate in people with Glioblastoma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This clinical trial studies disulfiram in treating patients with glioblastoma multiforme (GBM) who have completed radiation therapy with temozolomide. Disulfiram may block some of the enzymes needed for tumor cell growth and improve clinical outcome in GBM patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Temozolomide, Disulfiram and Copper gluconate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2013to 9 Feb 2018
- Phase
- Early Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of histologically confirmed GBM (WHO grade IV).
- At least 18 years of age.
- ECOG performance status of at least 2.
- Has received or is in the process of completing a course of definitive radiotherapy of at least 45 Gy with concurrent temozolomide (patient may be registered before completing radiotherapy as long as it is anticipated that s/he will complete at least 45 Gy).
- Eligible for and planning to receive maintenance temozolomide after completion of definitive radiotherapy plus temozolomide.
- Willing to remain abstinent from consuming alcohol while on disulfiram.
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- Meets the following laboratory criteria:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin > 9.0 g/dL (transfusion and/or ESA allowed)
- Total bilirubin ≤ 2x institutional upper limit of normal (ULN)
- AST and ALT < 3 x ULN
- Calculated creatinine clearance must be > 60 mL/min (by Cockcroft-Gault)
- Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Able to take oral medication.
- Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).
Who cannot join
- Receipt of any other investigational agents within 14 days prior to study enrollment.
- Enrolled on another clinical trial testing a novel therapy or drug.
- History of allergic reaction to disulfiram.
- Treatment with clinically significant cytochromes P450 enzyme inducers, such as phenytoin, phenobarbital, chlordiazepoxide, diazepam, isoniazid, metronidazole, warfarin, amitriptyline within 14 days prior to the first dose of disulfiram. Of note, lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with disulfiram.
- Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, have New York Heart Association (NYHA) Class III or IV heart failure (Appendix B), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- History of idiopathic seizure disorder, psychosis or schizophrenia.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of initiation of treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma
This clinical trial studies disulfiram in treating patients with glioblastoma multiforme (GBM) who have completed radiation therapy with temozolomide. Disulfiram may block some of the enzymes needed for tumor cell growth and improve clinical outcome in GBM patients.
- Conditions
- Glioblastoma
- Being tested
- Temozolomide, Disulfiram, Copper gluconate
- 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
DisulfiramDrug
Also called Antabuse
Copper gluconateDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Maintenance Temozolomide + Disulfram | Experimental | Beginning 4-6 weeks after completion of radiation therapy, patients receive maintenance temozolomide 150-200 mg/m2 PO QD on Days 1-5 every 28 days for 6 months. Disulfiram (dose level 0 = 500 mg PO QD or dose level 1 1000 mg PO QD) on days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive additional maintenance temozolomide at the discretion of the treating medical oncologist. Receives: Drug: Temozolomide; Drug: Disulfiram |
| Maintenance Temozolomide + Disulfiarm + Copper Gluconate | Experimental | Beginning 4-6 weeks after completion of radiation therapy, patients receive maintenance temozolomide 150-200 mg/m2 PO QD on Days 1-5 every 28 days for 6 months, disulfiram 500 mg PO QD (dose of disulfiram determined to be the MTD) on Days 1-28, and copper gluconate 6 mg PO QD on Days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive additional maintenance temozolomide at the discretion of the treating medical oncologist. Receives: Drug: Temozolomide; Drug: Disulfiram; Dietary Supplement: Copper gluconate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacological effect of disulfiram in GBM patients
Degree of proteasome inhibition in peripheral white blood cells and rate of complete inhibition in GBM patients using descriptive statistics
Measured: 30 days
Secondary outcomes (2)
Local tumor control probabilities
The Kaplan-Meier product-limit method will be used.
Measured: 2 years
Time to tumor progression
Modeled using the Cox proportional hazard models.
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 posted24 Jul 2013 (estimated)
- Study start10 Oct 2013
- Primary completion10 Nov 2016
- Study completion9 Feb 2018
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 GlioblastomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jiayi Huang, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01907165
- Sponsor's protocol ID
- 201308038
- Status last verified
- Jul 2018
- First submitted
- 19 Jul 2013
- Last updated
- 20 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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 20 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacodynamic Study of Proteasome Inhibition by Disulfiram in Patients With Glioblastoma
- ClinicalTrials.gov ID
- NCT01907165
- Acronym / sponsor ID
- 201308038
- Conditions
- Glioblastoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 10 Oct 2013 (actual)
- Primary completion
- 10 Nov 2016 (actual)
- Study completion
- 9 Feb 2018 (actual)
- First posted
- 24 Jul 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.
This clinical trial studies disulfiram in treating patients with glioblastoma multiforme (GBM) who have completed radiation therapy with temozolomide. Disulfiram may block some of the enzymes needed for tumor cell growth and improve clinical outcome in GBM patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maintenance Temozolomide + Disulfram | Experimental | Drug: Temozolomide, Drug: DisulfiramBeginning 4-6 weeks after completion of radiation therapy, patients receive maintenance temozolomide 150-200 mg/m2 PO QD on Days 1-5 every 28 days for 6 months. Disulfiram (dose level 0 = 500 mg PO QD or dose level 1 1000 mg PO QD) on days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity. NOTE: *Patients may receive additional maintenance temozolomide at the discretion of the treating medical oncologist. |
| Maintenance Temozolomide + Disulfiarm + Copper Gluconate | Experimental | Drug: Temozolomide, Drug: Disulfiram, Dietary Supplement: Copper gluconateBeginning 4-6 weeks after completion of radiation therapy, patients receive maintenance temozolomide 150-200 mg/m2 PO QD on Days 1-5 every 28 days for 6 months, disulfiram 500 mg PO QD (dose of disulfiram determined to be the MTD) on Days 1-28, and copper gluconate 6 mg PO QD on Days 1-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity. 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 (16 listed)
- Diagnosis of histologically confirmed GBM (WHO grade IV).
- At least 18 years of age.
- ECOG performance status of at least 2.
- Has received or is in the process of completing a course of definitive radiotherapy of at least 45 Gy with concurrent temozolomide (patient may be registered before completing radiotherapy as long as it is anticipated that s/he will complete at least 45 Gy).
- Eligible for and planning to receive maintenance temozolomide after completion of definitive radiotherapy plus temozolomide.
Key exclusion criteria (7 listed)
- Receipt of any other investigational agents within 14 days prior to study enrollment.
- Enrolled on another clinical trial testing a novel therapy or drug.
- History of allergic reaction to disulfiram.
- Treatment with clinically significant cytochromes P450 enzyme inducers, such as phenytoin, phenobarbital, chlordiazepoxide, diazepam, isoniazid, metronidazole, warfarin, amitriptyline within 14 days prior to the first dose of disulfiram. Of note, lorazepam and oxazepam are not affected by the P450 system and are not contraindicated with disulfiram.
- Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, have New York Heart Association (NYHA) Class III or IV heart failure (Appendix B), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
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: Temodar | Drug | Maintenance Temozolomide + Disulfiarm + Copper Gluconate, Maintenance Temozolomide + Disulfram |
| DisulfiramAlso: Antabuse | Drug | Maintenance Temozolomide + Disulfiarm + Copper Gluconate, Maintenance Temozolomide + Disulfram |
| Copper gluconate | Dietary supplement | Maintenance Temozolomide + Disulfiarm + Copper Gluconate |
Primary outcome
Pharmacological effect of disulfiram in GBM patients
Time frame: 30 days
Degree of proteasome inhibition in peripheral white blood cells and rate of complete inhibition in GBM patients using descriptive statistics
2 secondary outcomes
Local tumor control probabilities
Time frame: 2 years
Time to tumor progression
Time frame: 2 years
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 20 Jul 2018.
- 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.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- 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.
Jiayi Huang, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Temozolomide, Disulfiram and Copper gluconate in people with Glioblastoma, run by Washington University School of Medicine 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 16 inclusion and 7 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 20 Jul 2018. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Pharmacological effect of disulfiram in GBM patients (time frame: 30 days). 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 NCT01907165, 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 20 Jul 2018.