GlioblastomaEarly Phase 1INSIDENCT03151772
Bioavailability of Disulfiram and Metformin in Glioblastomas
A Early Phase 1 study testing Disulfiram and Metformin in people with Glioblastoma, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial summary
Neuro-oncological trials may fail due to the drug never getting to the intended target (i.e. within the tumor micro environment). Also, changes' occurring in tumor cells when removed from patients and grown in-vitro is another limiting factor influencing the clinical success. Important questions are therefore: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Disulfiram and Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteSweden
- Study dates
- 29 Jan 2018to 24 Sep 2020
- 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
- The subjects must fulfill all the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:
- A suspected glioblastoma (based on MRI) or recurrent glioblastoma undergoing surgical resection.
- Elective surgical indication
- Age 18 years or older.
- Karnofsky performance status of 60 - 100 (see attachment 3).
- Not receiving another experimental treatment for glioblastoma at the moment of inclusion.
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- Able to take oral medications.
- No known allergy to substance
- Absolute neutrophil count ≥ 1,500/mcL and platelets ≥ 100,000/mcL
Who cannot join
- General
- Other likely diagnosis than glioblastoma based on MRI.
- Pregnant and/or breastfeeding.
- Women of childbearing potential who do not have a negative pregnancy test (not older than 14 days) before inclusion.
- History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology or toxic hepatitis or inadequate hepatic function, defined as baseline ASAT and ALAT > 1.5 X upper institutional limit and/or bilirubin > 1.5 X upper institutional limit.
- Suspected significant raised intracranial pressure or other indication for emergent surgery
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- Unfit for participation for any other reason judged by the including physician.
- Specific additional exclusions criteria for disulfiram
- History of uncontrolled hypertension (i.e. systolic BP > 180 mmHg) and a diagnosis of congestive heart failure
- History of psychiatric conditions (e.g. depression, psychosis, schizophrenia) or dementia.
- History of Wilson's disease or family member with Wilson's disease (unless excluded as a carrier by genetic test).
- History of hemochromatosis or family member with hemochromatosis (unless excluded as a carrier by genetic test).
- Nickel hypersensitivity (disulfiram mobilize nickel causing a brief increase in nickel concentrations before excretion. The initial increase may lead to hepatitis and predisposed patients).7
- Need for metronidazole, warfarin and/or theophylline medication (the metabolism may be influenced by disulfiram).
- Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives (phenytoin, phenobarbital, chlordiazepoxide, imipramine, 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).
- Addiction to alcohol or drugs. Alcohol must be avoided.
- Serum/plasma copper and serum ceruloplasmin outside institutional limits. a. However increased levels are seen together with ongoing acute phase reaction as determined by elevated C-reactive protein (ceruloplasmin is elevated as part of the same process) it is possible to retest after normalization of C-reactive protein.
- Specific additional exclusions criteria for metformin
- Diabetic patients or other patients where treating physician and/or anesthesiologist consider may have an increased risk for lactic acidosis per- and postoperatively
- Known renal failure, renal risk factors (including single kidney, donor kidney, polycystic kidneys) or estimated glomerular filtration rate below 80 ml/min.
- Congestive heart failure
- Scheduled diagnostic work-up where contrast medium containing iodine is indicated
- Concomitant use of NSAIDs (risk of renal injury)
- Risk of dehydration judged by the treating physician (e.g. when symptoms include vomiting)
- Alcohol must be avoidance during treatment (increased risk of lactic acidosis)
- Treatment with diuretics as they may increase risk of lactic acidosis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Drug Level and Investigation of Novel Substances Indicated Downstream Effect in Glioblastoma
Neuro-oncological trials may fail due to the drug never getting to the intended target (i.e. within the tumor micro environment). Also, changes' occurring in tumor cells when removed from patients and grown in-vitro is another limiting factor influencing the clinical success.
Important questions are therefore:
- Does the drug get there?
- Does the drug do what it is intended to do?
To improve chances of clinical success there is a need for rational and intelligent selection of potential drugs in future trials. This is an initiative for analyzing tumor concentration of preoperative administered repurposed drugs
- Conditions
- Glioblastoma
- Being tested
- Disulfiram, Metformin
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
200 mg disulfiram two times daily and 2,5 mg copper once daily taken preoperatively
MetforminDrug
Metformin 850 mg x 3 taken preoperatively
| Study group | Role | What they receive |
|---|---|---|
| Disulfiram | Experimental | Disulfiram 200 mg twice daily and copper 2,5 mg once daily. For bioavailability purpose only, treatment is withdrawn postoperatively Receives: Drug: Disulfiram |
| Metformin | Experimental | Metformin 850 mg x 3 daily. For bioavailability purpose only, treatment is withdrawn postoperatively Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bioavailabilty disulfiram
Concentration of disulifram-copper complex available in glioblastoma compared to blood
Measured: At time of surgery
Bioavailabilty of metformin
Concentration of metformin available in glioblastoma compared to blood
Measured: At time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start29 Jan 2018
- Primary completion24 Sep 2020
- Study completion24 Sep 2020
Why it stopped: Problems with including patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Bioavailability study with an adaptive design (evaluation after 5 patients up to a total maximum of 20 patients in each arm). Experimental therapy not to be combined and not any comparison between therapies
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asgeir S. Jakola, Sahlgrenska University Hospital
- Investigators
- Asgeir S Jakola, MD, PhD, Principal investigator, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03151772
- Sponsor's protocol ID
- 1144-16
- Acronym
- INSIDE
- Status last verified
- Sep 2020
- First submitted
- 9 May 2017
- Last updated
- 28 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug Level and Investigation of Novel Substances Indicated Downstream Effect in Glioblastoma
- ClinicalTrials.gov ID
- NCT03151772
- Acronym / sponsor ID
- INSIDE / 1144-16
- Conditions
- Glioblastoma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Problems with including patients
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Study start
- 29 Jan 2018 (actual)
- Primary completion
- 24 Sep 2020 (actual)
- Study completion
- 24 Sep 2020 (actual)
- First posted
- 12 May 2017 (actual)
- 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.
Neuro-oncological trials may fail due to the drug never getting to the intended target (i.e. within the tumor micro environment). Also, changes' occurring in tumor cells when removed from patients and grown in-vitro is another limiting factor influencing the clinical success.
Important questions are therefore:
- Does the drug get there?
- Does the drug do what it is intended to do?
To improve chances of clinical success there is a need for rational and intelligent selection of potential drugs in future trials. This is an initiative for analyzing tumor concentration of preoperative administered repurposed drugs
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Bioavailability study with an adaptive design (evaluation after 5 patients up to a total maximum of 20 patients in each arm). Experimental therapy not to be combined and not any comparison between therapies
| Arm | Type | Receives |
|---|---|---|
| Disulfiram | Experimental | Drug: DisulfiramDisulfiram 200 mg twice daily and copper 2,5 mg once daily. For bioavailability purpose only, treatment is withdrawn postoperatively |
| Metformin | Experimental | Drug: MetforminMetformin 850 mg x 3 daily. For bioavailability purpose only, treatment is withdrawn postoperatively |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- The subjects must fulfill all the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:
- A suspected glioblastoma (based on MRI) or recurrent glioblastoma undergoing surgical resection.
- Elective surgical indication
- Age 18 years or older.
- Karnofsky performance status of 60 - 100 (see attachment 3).
Key exclusion criteria (26 listed)
- General
- Other likely diagnosis than glioblastoma based on MRI.
- Pregnant and/or breastfeeding.
- Women of childbearing potential who do not have a negative pregnancy test (not older than 14 days) before inclusion.
- History of active liver disease, including chronic active hepatitis, viral hepatitis (hepatitis B, C and CMV), cholestatic jaundice of any etiology or toxic hepatitis or inadequate hepatic function, defined as baseline ASAT and ALAT > 1.5 X upper institutional limit and/or bilirubin > 1.5 X upper institutional limit.
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 |
|---|---|---|
| Disulfiram200 mg disulfiram two times daily and 2,5 mg copper once daily taken preoperatively | Drug | Disulfiram |
| MetforminMetformin 850 mg x 3 taken preoperatively | Drug | Metformin |
Primary outcome
Bioavailabilty disulfiram
Time frame: At time of surgery
Concentration of disulifram-copper complex available in glioblastoma compared to blood
Bioavailabilty of metformin
Time frame: At time of surgery
Concentration of metformin available in glioblastoma compared to blood
Results and safety
The study was stopped early (reason given: Problems with including patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2020.
- 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.
Asgeir S Jakola, MD, PhD principal investigator
Sahlgrenska University Hospital
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 Disulfiram and Metformin in people with Glioblastoma, run by Sahlgrenska University Hospital at 1 site in Sweden.
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 9 inclusion and 26 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: stopped early, as of the sponsor's last update on 28 Sep 2020. 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 Sweden. 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 was stopped early (reason given: Problems with including patients). Results are not available in the source record.
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?
Bioavailabilty disulfiram (time frame: At time of surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Sep 2020.