DIsulfiram REsponse as add-on to ChemoTherapy in recurrent Glioblastoma: A randomized controlled trial

Phase 1

• Conditions: Glioblastoma; MedDRA version: 19.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2016-000167-16-NO
• Lead Sponsor: Sahlgrenska University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-04-18
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

1. A previous diagnosis of glioblastoma (histologically verified) and presenting with a first progression/recurrence documented by MRI.
2. Indication for treatment with chemotherapeutic alkylating agents (i.e. temozolomide OR lomustine (also known as CCNU) including the so called PCV treatment (procarbazine, CCNU, vincristine)).
3. Age 18 years or older.
4. Karnofsky performance status of 60 – 100
5. Willing to refrain from ingestion of alcoholic beverages
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1. Earlier treatment for progression
2. Received radiotherapy within the 3 months before the diagnosis of progression
3. History of idiopathic seizure disorder, psychosis or schizophrenia.
4. History of uncontrolled hypertension (i.e. systolic BP > 180 mmHg) or a diagnosis of congestive heart failure
5. History of active liver disease
6. History of Wilson's disease or family member with Wilson's disease (unless excluded as a carrier by genetic test).
7. Use of medications such as metronidazole, warfarin, theophylline, phenytoin, phenobarbital, chlordiazepoxide, imipramine, diazepam, isoniazid, 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).
8. Unfit for participation for any other reason judged by the physician including patients

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the effect on survival at 6 months of disulfiram and copper-supplement as add-on treatment in glioblastoma patients receiving alkylating chemotherapy. This will to our knowledge be the first planned RCT with disulfiram in glioblastoma patients, and will consequently serve as a proof-of concept study. ;Secondary Objective: To investigate in glioblastoma patients receiving alkylating chemotherapy the effect of disulfiram and copper-supplement as add-on treatment on:<br>- actual survival analyzed at 9, 12 and 24 months, <br>- median progression free survival,<br>- 6 and 12 month progression free survival<br>- median overall survival<br>- health-related quality of life<br>- volumetric expansion of the glioblastoma.<br>- toxicity/safety of disulfiram and copper-supplement<br> ;Primary end point(s): Survival;Timepoint(s) of evaluation of this end point: 6 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Actual survival<br>- Median progression free survival<br>- progression free survival <br>- Median overall survival <br>- Health-related quality of life<br>- Volumetric expansion<br>- Toxicity/safety;Timepoint(s) of evaluation of this end point: - at 9, 12 and 24 months (actual survival)<br>- at 6 and 12 months (progression free survival)