Disulfiram/Copper With Concurrent Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

April 9, 2025 updated by: Washington University School of Medicine

A Phase I/II Dose-escalation and Dose-expansion Study of Disulfiram/Copper With Concurrent Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

The proposed phase I/II study of disulfiram (DSF) for patients with presumed glioblastoma multiforme (GBM) based on magnetic resonance imaging (MRI) or biopsy, including administration before surgery and during adjuvant chemoradiotherapy. Patients will be treated with 3 days of preoperative DSF/copper (Cu) prior to their surgery (or biopsy), which will be followed by collection of tumor samples during surgery for analysis of drug uptake. After the surgery, patients will receive standard radiation therapy (RT) and temozolomide (TMZ) with the addition of concurrent DSF/Cu.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of GBM or its histological variants (WHO grade IV). Patients who are participating in the optional preoperative pharmacokinetic study, may have presumed GBM based on clinical/radiological findings. However, patient must have histologically confirmed GBM before continuing to receive DSF with concurrent RT/TMZ.
  • Expansion Cohort: must have a diagnosis of GBM (or its histological variants) with IDH, BRAF, or NF1 mutations. Confirmation of these mutations may be either by immunohistochemistry or next-generation sequencing
  • At least 18 years of age.
  • Karnofsky performance status (KPS) of at least 60%
  • For patients who will participate in the optional pre-operative DSF pharmacokinetic study, they should be eligible for surgical resection for which at least 0.2 cubic cm or approximately 200 mg of tumor will be removed in additional to tumor specimen required for pathology evaluation. Patients enrolled after undergoing surgical resection or biopsy with histologically confirmed GBM are not required to meet this point of inclusion.
  • Eligible for and planning to receive standard fractionated RT with concurrent TMZ.
  • Willing to remain abstinent from consuming alcohol while on DSF.
  • Willing to defer definitive surgery for one week while taking DSF and Cu. Patients who declined the optional pre-operative pharmacokinetic study or enrolled after undergoing surgical resection or biopsy with histologically confirmed GBM are not required to meet this point of inclusion.

  • Meets the following laboratory criteria:

    • Absolute neutrophil count ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcL
    • Hemoglobin > 10.0 g/dL (transfusion and/or ESA allowed)
    • Total bilirubin ≤ 2x institutional upper limit of normal (ULN)
    • AST and ALT < 3 x ULN
    • Serum creatinine < 1.5 x ULN or creatinine clearance > 50 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).

Exclusion Criteria:

  • Receipt of any other investigational agents within 14 days prior to study treatment
  • Enrolled on another clinical trial testing a novel therapy or drug.
  • History of allergic reaction to DSF or Cu.
  • Treatment with the following medications are contraindicated with DSF when taken within 7 days prior to the first dose of DSF + Cu: metronidazole, isoniazid, dronabinol, carbocisteine, lopinavir, paraldehyde, ritonavir, sertaline, tindazole, tixanidine, atazanavir. (Note: the following medications are not contraindicated but should be cautioned if taking concurrently with DSF: warfarin, phenytoin, theophylline, chlorzoxazone, chlordiazepoxide, diazepam. If the patient is taking warfarin, INR should be monitored closely. If the patient has to remain on phenytoin, its serum concentration and response should be monitored closely.
  • Active or severe hepatic, cardiovascular, or cerebrovascular disease, including myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, 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.
  • History of Wilson's disease or family member with Wilson's disease.
  • History of hemochromatosis or family member with hemochromatosis.
  • Pregnant and breastfeeding women will be excluded because of the known teratogenic effect of RT and the unknown effect of TMZ and DSF on fetal development. Women of childbearing potential must have a negative pregnancy test within 14 days of initiation of treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 2)
  • Disulfiram (DSF) dose level 2=250mg.
  • Preoperative DSF/Copper (CU) x 3 days (optional)
  • Surgery performed per routine clinical care.
  • After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study).
  • Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions.
  • Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care.
  • DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose.
  • 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
Drug: Temozolomide
Other Names:
  • Temodar®
Procedure: Surgery
Radiation: Radiation
Drug: Disulfiram
Other Names:
  • DSF
  • Antabuse®
Drug: Copper Gluconate
Other Names:
  • Copper
  • Cu
Experimental: Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 3)
  • Disulfiram (DSF) dose level 3=375mg.
  • Preoperative DSF/Copper (CU) x 3 days (optional)
  • Surgery performed per routine clinical care.
  • After surgery, evaluation to confirm the final pathological diagnosis as GBM (if not the patient will not continue with the 2nd part of the study).
  • Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions.
  • Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care.
  • DSF daily and Cu three times daily during chemoradiotherapy as per preoperative dose.
  • 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
Drug: Temozolomide
Other Names:
  • Temodar®
Procedure: Surgery
Radiation: Radiation
Drug: Disulfiram
Other Names:
  • DSF
  • Antabuse®
Drug: Copper Gluconate
Other Names:
  • Copper
  • Cu
Experimental: Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose expansion)
  • Surgery performed per routine clinical care.
  • Radiation therapy (RT) 4-6 weeks following surgery at 60 Gy in 30 daily fractions.
  • Temozolomide (TMZ) from Day 1 of RT to the last day of RT at a daily oral dose for a maximum of 49 days as per standard clinical care.
  • Disulfiram (DSF) daily (250 mg) and Copper (Cu) three times daily during chemoradiotherapy.
  • 4-6 weeks after completion of chemoradiotherapy, adjuvant TMZ may be administered for 6 cycles. TMZ on Days 1-5 of every 28-day cycle. Daily DSF of 500mg will be continued with adjuvant TMZ for up to 6 cycles.
  • If a patient develops recurrent tumor during follow-up and plans to undergo another resection, he/she may opt for an optional preoperative DSF study prior to salvage surgery.
Drug: Temozolomide
Other Names:
  • Temodar®
Procedure: Surgery
Radiation: Radiation
Drug: Disulfiram
Other Names:
  • DSF
  • Antabuse®
Drug: Copper Gluconate
Other Names:
  • Copper
  • Cu

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of DSF (Dose-escalation Phase Only)
Time Frame: Estimated to be 2 years and 28 weeks
  • The maximum tolerated dose (MTD) of DSF is defined as the dose level at which 20% of the cohort experience dose-limiting toxicity (DLT) within 18 weeks from start of RT (or 12 weeks from the end of RT if there is a delay in RT). MTD is assessed from the first dose of DSF in combination with TMZ and RT; patients will not be assessed for DLT during the pre-surgery period when they are receiving the lead-in doses of DSF.
  • A DLT is defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications/TMZ which occurs within 18 weeks following the first dose of DSF with RT+TMZ (corresponding to approximately 6 weeks during RT and 12 weeks after RT)
Estimated to be 2 years and 28 weeks
Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)
Time Frame: 1 year
1 year
Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)
Time Frame: 2 years
2 years
Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)
Time Frame: 3 years
3 years
Mean Overall Survival (Dose-expansion Phase Only)
Time Frame: Through completion of follow-up (up to 5 years)
Through completion of follow-up (up to 5 years)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Toxicity of DSF When Given Concurrently With Radiation Therapy and Temozolomide as Measured by the Grade and Frequency of Grade 2 or Greater Adverse Events Related to DSF
Time Frame: Through completion of DSF treatment (up to 38 weeks)
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Through completion of DSF treatment (up to 38 weeks)
Intratumor and Plasma Concentration of DSF Metabolite (Ditiocarb-copper Complex)
Time Frame: At the time of surgery (day 4)
Will be determined using mass spectrometer
At the time of surgery (day 4)
Mean Progression-free Survival (PFS)
Time Frame: Through completion of follow-up (up to 5 years)
Will be determined from the first day of RT to the time of tumor progression or death, whichever occurs first. Tumor progression will be determined using the RANO criteria.
Through completion of follow-up (up to 5 years)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Rate of Pseudo-progression (PsP)
Time Frame: Through completion of follow-up (up to 5 years)
-Pseudoprogression is defined as a transient increase of tumor after chemoradiotherapy that subsequently stabilizes without a change of therapy
Through completion of follow-up (up to 5 years)
Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Glutamine Levels in Plasma and Tumor Tissues
Time Frame: Week 6
Week 6
Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Glutamate Levels in Plasma and Tumor Tissues
Time Frame: Week 6
Week 6
Time to Tumor Progression (TTP) (Dose-escalation Phase Only)
Time Frame: Through completion of follow-up (up to 5 years)

-≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids. The absolute increase in any dimension must be at least 5mm when calculating the products

  • Significant increase in T2/FLAIR nonenhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy not caused by comorbid events
  • Any new measureable lesion
  • Clear clinical deterioration not attributable to other causes apart from the tumor (e.g. seizures, medication adverse effects, complications of therapy, cerebrovascular events, infection, and so on) or changes in corticosteroid dose
  • Failure to return for evaluation as a result of death or deteriorating condition; or clear progression of nonmeasurable disease
Through completion of follow-up (up to 5 years)
Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Aspartate Levels in Plasma and Tumor Tissues
Time Frame: Week 6
Week 6
Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Glucose Levels in Plasma and Tumor Tissues
Time Frame: Week 6
Week 6
Pharmacodynamic Studies on Glutamate Metabolism as Measured by Measurement of Lactate Levels in Plasma and Tumor Tissues
Time Frame: Week 6
Week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jiayi Huang, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 15, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 12, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 12, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 9, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 22, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 10, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201604115

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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