Glioma, MalignantPhase 1NCT04091503
Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma
A Phase 1 study testing Intranasal Modified Temozolomide in people with Glioma, Malignant and Gliosarcoma, run by Center Trials & Treatment Europe at 3 sites in 3 countries.
Trial summary
The purpose of this pilot study is to determine the safety, tolerability, and the maximum tolerated dose intranasal administration of temozolomide (TMZ) as a single agent in Treatment on the patients with GBM. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Glioma, Malignant, Gliosarcoma, Astrocytoma of Brain
- What is being tested?
- Intranasal Modified Temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 20 Dec 2019to 28 Oct 2022
- Phase
- 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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent signed
- 21 years or older
- Histologically confirmed the diagnosis of Grade 4 astrocytic tumour, which includes glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with oligodendroglial components
- The availability of histological material for the possibility of revising histological verification
- IDH 1 Mutation and IDH2 Mutation are not taken into account when enrolling in that study
- MGMT promoter methylation MUST BE CONFIRMED
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- Must have a Karnofsky performance status of ≥ 70% and the ability to use intranasal administration
- Sexually active fertile subjects (male and female) must agree to use accepted methods of contraception during the course of the study and for 3 months after the last intranasal administration of Temozolomide
- Female subjects of childbearing potential must have a negative pregnancy test at screening.
- Must be capable of understanding and complying with the protocol requirements
Who cannot join
- History of hypersensitivity to TMZ or any of its excipients
- The subject has had major surgery within 28 days prior to starting study treatment, or had non-water-tight dural closure during previous surgery, or has unhealed wounds from previous surgery
- The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
- The subject is pregnant or breastfeeding
- The subject suffered a stroke according to the results of the first MRI upon admission
- Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (haematological and bone marrow suppression effects), generally at least 3 weeks from the most recent administration (6 weeks for nitrosoureas). Subjects may not have received more than 1 cycle of Irinotecan and Temozolomide as previous relapse therapy
- Subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: Pilot Study to Evaluate the Safety, Tolerability and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma (Phase I)
The purpose of this pilot study is to determine the safety, tolerability, and the maximum tolerated dose intranasal administration of temozolomide (TMZ) as a single agent in Treatment on the patients with GBM.
Intranasal administration is a new method of treating brain tumours for the direct administration of drugs, inhibitors or viruses, with minimal involvement of the BBB. The investigators know the orally prescribed standard chemotherapy temozolomide (TMZ) is widely used to treat glioma tumours.
Read more
Received evidence of safety and efficacy in a full cycle of preclinical trials (on GLP Standart) and tests of calculated doses of intranasal administration of TMZ in healthy volunteers.
Intranasal administration of temozolomide is considered as GBM therapy, which provides direct access to a therapeutic dose of the drug into the brain (to the neoplastic process) with low toxicity
Read the detailed description
The investigators are trying to evaluate a clinically potentially effective intranasal way of delivering TMZ to the brain, taking into account the anatomical structure of os ethmoidal.
The most important factor in the effectiveness of the drug is the achievement of an adequate amount of the active agent in its unbound state with albumin on the blood of a patient and the exposure time to the tumour process. Failure to comply with this requirement (difficulties in overcoming the BBB) was identified as the main obstacle to the successful treatment of all types of brain tumours. Translation to improved clinical outcomes in a patient with GBM has not yet been realized. The investigators will use modified temozolomide (without changing the chemical formula) to exclude as much as possible Anosmia, Hyposmia and other violation of the identification of odours with participants.
- Conditions
- Glioma, Malignant, Gliosarcoma, Astrocytoma of Brain
- Being tested
- Intranasal Modified Temozolomide
- Keywords
- TMZ, Temozolomide, Intranasal Administration, Nasal Spray, Intranasal Modified Temozolomide
- Medical subject headings
- Glioma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal Modified TemozolomideDrug
Also called Temozolomide, TMZ, IM-TMZ
Intranasally Modified Temozolomide is administered to patients at a dose of 75/150/200 mg / M2 for five days continuously. After the 5-day course, patients do not take treatment for two days, and they will be examined on an outpatient basis (blood tests, kidney and liver tests, visually mucous membranes of the mouth, nasal cavity, olfactory rapid tests, including the University of Pennsylvania test, etc.).
After 30 days after the first intranasal administration of Modified Temozolomide (IM-TMZ), all patients undergo an MRI of the brain with perfusion and ultrasound of the abdominal cavity as an outpatient, after which the results are evaluated
| Study group | Role | What they receive |
|---|---|---|
| Intranasal Modified Temozolomide 75 mg/M2 per day | Active comparator | 75 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days) Receives: Drug: Intranasal Modified Temozolomide |
| Intranasal Modified Temozolomide 150 mg/M2 per day | Active comparator | 150 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days) Receives: Drug: Intranasal Modified Temozolomide |
| Intranasal Modified Temozolomide 200 mg/M2 per day | Active comparator | 200 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days) Receives: Drug: Intranasal Modified Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The randomized study to determine the safety of Intranasal Administration of modified Temozolomide.
Incidence of Treatment-Emergent Adverse Events will be estimated by the number of participants with Glioblastoma or Gliosarcoma according to the NCI CTC (5.0) with adverse events (AE) in all cohorts.
Measured: up to 60 days (or withdrawal of consent or another discontinuation criterion) from date of randomization
Secondary outcomes (1)
The maximum tolerated therapeutic dose (MTD) of modified Temozolomide for intranasal administration
In the present study, the maximum dose of modified Temozolomide for intranasal administration is 200 mg / M2 a single daily intranasal administration in a course of 5 days. The frequency of adverse events, unacceptable toxicity, or haematological reactions is estimated on a scale the NCI CTCAE (v. 5.0)
Measured: up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2019
- Study start20 Dec 2019
- Primary completion21 Sep 2022
- Study completion28 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioma, MalignantStudies of the same condition, open and under way.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Parallel Assignment
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center Trials & Treatment Europe
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04091503
- Sponsor's protocol ID
- 7SQZ309D4W
- Status last verified
- Apr 2023
- First submitted
- 8 Sep 2019
- Last updated
- 25 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- 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 25 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Evaluate the Safety, Tolerability and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma (Phase I)
- ClinicalTrials.gov ID
- NCT04091503
- Acronym / sponsor ID
- 7SQZ309D4W
- Conditions
- Glioma, Malignant, Gliosarcoma, Astrocytoma of Brain
- Keywords
- TMZ, Temozolomide, Intranasal Administration, Nasal Spray, Intranasal Modified Temozolomide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Center Trials & Treatment EuropeResearch network
- Study start
- 20 Dec 2019 (actual)
- Primary completion
- 21 Sep 2022 (actual)
- Study completion
- 28 Oct 2022 (actual)
- First posted
- 16 Sep 2019 (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.
The purpose of this pilot study is to determine the safety, tolerability, and the maximum tolerated dose intranasal administration of temozolomide (TMZ) as a single agent in Treatment on the patients with GBM.
Intranasal administration is a new method of treating brain tumours for the direct administration of drugs, inhibitors or viruses, with minimal involvement of the BBB. The investigators know the orally prescribed standard chemotherapy temozolomide (TMZ) is widely used to treat glioma tumours.
Received evidence of safety and efficacy in a full cycle of preclinical trials (on GLP Standart) and tests of calculated doses of intranasal administration of TMZ in healthy volunteers.
Intranasal administration of temozolomide is considered as GBM therapy, which provides direct access to a therapeutic dose of the drug into the brain (to the neoplastic process) with low toxicity
Detailed description
The investigators are trying to evaluate a clinically potentially effective intranasal way of delivering TMZ to the brain, taking into account the anatomical structure of os ethmoidal.
The most important factor in the effectiveness of the drug is the achievement of an adequate amount of the active agent in its unbound state with albumin on the blood of a patient and the exposure time to the tumour process. Failure to comply with this requirement (difficulties in overcoming the BBB) was identified as the main obstacle to the successful treatment of all types of brain tumours. Translation to improved clinical outcomes in a patient with GBM has not yet been realized. The investigators will use modified temozolomide (without changing the chemical formula) to exclude as much as possible Anosmia, Hyposmia and other violation of the identification of odours with participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 3
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Intranasal Modified Temozolomide 75 mg/M2 per day | Active comparator | Drug: Intranasal Modified Temozolomide75 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days) |
| Intranasal Modified Temozolomide 150 mg/M2 per day | Active comparator | Drug: Intranasal Modified Temozolomide150 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days) |
| Intranasal Modified Temozolomide 200 mg/M2 per day | Active comparator | Drug: Intranasal Modified Temozolomide200 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days) |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Informed consent signed
- 21 years or older
- Histologically confirmed the diagnosis of Grade 4 astrocytic tumour, which includes glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with oligodendroglial components
- The availability of histological material for the possibility of revising histological verification
- IDH 1 Mutation and IDH2 Mutation are not taken into account when enrolling in that study
Key exclusion criteria (7 listed)
- History of hypersensitivity to TMZ or any of its excipients
- The subject has had major surgery within 28 days prior to starting study treatment, or had non-water-tight dural closure during previous surgery, or has unhealed wounds from previous surgery
- The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
- The subject is pregnant or breastfeeding
- The subject suffered a stroke according to the results of the first MRI upon admission
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 |
|---|---|---|
| Intranasal Modified TemozolomideAlso: Temozolomide, TMZ, IM-TMZIntranasally Modified Temozolomide is administered to patients at a dose of 75/150/200 mg / M2 for five days continuously. After the 5-day course, patients do not take treatment for two days, and they will be examined on an outpatient basis (blood tests, kidney and liver tests, visually mucous membranes of the mouth, nasal cavity, olfactory rapid tests, including the University of Pennsylvania test, etc.). After 30 days after the first intranasal administration of Modified Temozolomide (IM-TMZ), all patients undergo an MRI of the brain with perfusion and ultrasound of the abdominal cavity as an outpatient, after which the results are evaluated | Drug | Intranasal Modified Temozolomide 150 mg/M2 per day, Intranasal Modified Temozolomide 200 mg/M2 per day, Intranasal Modified Temozolomide 75 mg/M2 per day |
Primary outcome
The randomized study to determine the safety of Intranasal Administration of modified Temozolomide.
Time frame: up to 60 days (or withdrawal of consent or another discontinuation criterion) from date of randomization
Incidence of Treatment-Emergent Adverse Events will be estimated by the number of participants with Glioblastoma or Gliosarcoma according to the NCI CTC (5.0) with adverse events (AE) in all cohorts.
1 secondary outcome
The maximum tolerated therapeutic dose (MTD) of modified Temozolomide for intranasal administration
Time frame: up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intranasal Modified Temozolomide in people with Glioma, Malignant and Gliosarcoma, run by Center Trials & Treatment Europe at 3 sites in 3 countries.
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 10 inclusion and 7 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 25 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Bosnia and Herzegovina, Bulgaria, Georgia. 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?
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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The randomized study to determine the safety of Intranasal Administration of modified Temozolomide. (time frame: up to 60 days (or withdrawal of consent or another discontinuation criterion) from date of randomization). 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 25 Apr 2023.