Clinical trial NCT04091503: Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma
Official title: Pilot Study to Evaluate the Safety, Tolerability and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma (Phase I)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioma, Malignant
Gliosarcoma
Astrocytoma of Brain
Keywords: TMZ
Temozolomide
Intranasal Administration
Nasal Spray
Intranasal Modified Temozolomide
Lead sponsor: Center Trials & Treatment Europe
Sponsor class: NETWORK
First posted: 2019-09-16
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: The randomized study to determine the safety of Intranasal Administration of modified Temozolomide.
timeFrame: up to 60 days (or withdrawal of consent or another discontinuation criterion) from date of randomization
Secondary outcomes:
measure: The maximum tolerated therapeutic dose (MTD) of modified Temozolomide for intranasal administration
timeFrame: up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization
Other outcomes:
measure: Percentage of Participants Alive 6 Months After Start of Treatment of Temozolomide for intranasal administration
timeFrame: 180 days
measure: The effectiveness of intranasal administration of modified Temozolomide
timeFrame: up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization
Locations:
city: Banja Luka
country: Bosnia and Herzegovina
facility: Central Contact
city: Plovdiv,
country: Bulgaria
facility: Central Contact
city: Tbilisi
country: Georgia
facility: Central Contact
Study officials:
References: