NCT02678975

DIRECT (DIsulfiram REsponse as add-on to ChemoTherapy in Recurrent) Glioblastoma: A Randomized Controlled Trial

Completed Phase 2/Phase 3 Last updated 16 March 2021

What this trial tests

Phase 2/Phase 3 trial testing Disulfiram in Glioma in 88 participants. Completed in 15 January 2021.

Timeline

1 January 2017

Primary endpoint
15 January 2021

15 January 2021

Quick facts

Lead sponsor	Sahlgrenska University Hospital
Phase	Phase 2/Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	88
Start date	1 January 2017
Primary completion	15 January 2021
Estimated completion	15 January 2021
Sites	8 locations across Norway, Sweden

Drugs / interventions tested

• Disulfiram (DISULFIRAM) — full drug profile →
• Copper (COPPER) — full drug profile →
• Alkylating Agents — full drug profile →

Conditions studied

• Glioma — all drugs for Glioma →
• Glioblastoma — all drugs for Glioblastoma →

Sponsor

Sahlgrenska University Hospital

Who can join

18 and older, any sex, with Glioma or Glioblastoma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Survival 6 mo
  Time frame: Proportion of alive participants at 6 months

Sponsor's own description

Disulfiram (Antabuse®) is a well-tolerated, cheap, generic drug that has been in use since the 1950s to treat alcoholism. There is now an increasing amount of independent preclinical data to support disulfiram as an anticancer agent. The potency of disulfiram as an anticancer agent seems strengthened by copper.

The investigators aim is to investigate disulfiram and copper-supplement as add-on treatment in glioblastoma patients with recurrence receiving alkylating chemotherapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cuproptosis: mechanisms and links with cancers.
   Xie J, Yang Y, Gao Y, He J. · · 2023 · cited 510× · PMID 36882769 · DOI 10.1186/s12943-023-01732-y
2. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.
   Lin H, Liu C, Hu A, Zhang D, et al · · 2024 · cited 232× · PMID 38720342 · DOI 10.1186/s13045-024-01544-7
3. Small Molecule NF-κB Pathway Inhibitors in Clinic.
   Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
4. Recurrent Glioblastoma: From Molecular Landscape to New Treatment Perspectives.
   Birzu C, French P, Caccese M, Cerretti G, et al · · 2020 · cited 141× · PMID 33375286 · DOI 10.3390/cancers13010047
5. Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance.
   Babak MV, Ahn D. · · 2021 · cited 125× · PMID 34440056 · DOI 10.3390/biomedicines9080852
6. Treatment options for progression or recurrence of glioblastoma: a network meta-analysis.
   McBain C, Lawrie TA, Rogozińska E, Kernohan A, et al · · 2021 · cited 105× · PMID 34559423 · DOI 10.1002/14651858.cd013579.pub2
7. Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents.
   Kannappan V, Ali M, Small B, Rajendran G, et al · · 2021 · cited 94× · PMID 34604310 · DOI 10.3389/fmolb.2021.741316
8. Targeting FROUNT with disulfiram suppresses macrophage accumulation and its tumor-promoting properties.
   Terashima Y, Toda E, Itakura M, Otsuji M, et al · · 2020 · cited 82× · PMID 32001710 · DOI 10.1038/s41467-020-14338-5