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Glioblastoma MultiformePhase 1/2NCT02715609

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

A Phase 1/2 study testing Disulfiram, Copper Gluconate and Surgery in people with Glioblastoma Multiforme, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. 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?
Disulfiram, Copper Gluconate and Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
15 Jun 2016to 12 May 2024
Phase
Phase 1/2
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

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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.

Being tested
Disulfiram, Copper Gluconate, Surgery, Radiation, Temozolomide
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 DSF, Antabuse®

  • Copper GluconateDrug

    Also called Copper, Cu

  • SurgeryProcedure or surgery

  • RadiationRadiation

  • TemozolomideDrug

    Also called Temodar®

Study groups in NCT02715609
Study groupRoleWhat they receive
Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 2)Experimental* 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.
Receives: Drug: Disulfiram; Drug: Copper Gluconate; Procedure: Surgery; Radiation: Radiation; Drug: Temozolomide
Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose escalation - dose level 3)Experimental* 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.
Receives: Drug: Disulfiram; Drug: Copper Gluconate; Procedure: Surgery; Radiation: Radiation; Drug: Temozolomide
Disulfiram, Copper, Surgery, Radiation therapy, Temozolomide (dose expansion)Experimental* 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.
Receives: Drug: Disulfiram; Drug: Copper Gluconate; Procedure: Surgery; Radiation: Radiation; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of DSF (Dose-escalation Phase Only)

    • 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)

    Measured: Estimated to be 2 years and 28 weeks

  2. Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)

    Measured: 1 year

  3. Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)

    Measured: 2 years

  4. Kaplan-Meier Estimate of Overall Survival (Dose-expansion Phase Only)

    Measured: 3 years

  5. Mean Overall Survival (Dose-expansion Phase Only)

    Measured: Through completion of follow-up (up to 5 years)

Secondary outcomes (3)

  1. 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

    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.

    Measured: Through completion of DSF treatment (up to 38 weeks)

  2. Intratumor and Plasma Concentration of DSF Metabolite (Ditiocarb-copper Complex)

    Will be determined using mass spectrometer

    Measured: At the time of surgery (day 4)

  3. Mean Progression-free Survival (PFS)

    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.

    Measured: Through completion of follow-up (up to 5 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2016 (estimated)
  2. Study start15 Jun 2016
  3. Primary completion12 May 2024
  4. Study completion12 May 2024

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02715609
Sponsor's protocol ID
201604115
Status last verified
Apr 2025
First submitted
9 Mar 2016
Last updated
10 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Huang J, Campian JL, DeWees TA, Skrott Z, Mistrik M, Johanns TM, Ansstas G, Butt O, Leuthardt E, Dunn GP, Zipfel GJ, Osbun JW, Abraham C, Badiyan S, Schwetye K, Cairncross JG, Rubin JB, Kim AH, Chheda MG. A Phase 1/2 Study of Disulfiram and Copper With Concurrent Radiation Therapy and Temozolomide for Patients With Newly Diagnosed Glioblastoma. Int J Radiat Oncol Biol Phys. 2024 Nov 1;120(3):738-749. doi: 10.1016/j.ijrobp.2024.05.009. Epub 2024 May 19.

    PubMed 38768767

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Disulfiram, Copper Gluconate and Surgery in people with Glioblastoma Multiforme, 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 18 inclusion and 9 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 10 Apr 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 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 10 Apr 2025). 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?

Maximum Tolerated Dose (MTD) of DSF (Dose-escalation Phase Only) (time frame: Estimated to be 2 years and 28 weeks). The study lists 5 primary outcomes in all. 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 NCT02715609, 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 10 Apr 2025.

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