Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma

NCT04091503 | Completed Phase 1 DMC

• 1 other identifier: 7SQZ309D4W
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 3

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

Conditions

Glioma, Malignant; Gliosarcoma; Astrocytoma of Brain

Keywords

TMZ; Temozolomide; Intranasal Administration; Nasal Spray; Intranasal Modified Temozolomide

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization

Other Outcomes (2)

• Percentage of Participants Alive 6 Months After Start of Treatment of Temozolomide for intranasal administration

  180 days

• The effectiveness of intranasal administration of modified Temozolomide

  up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization

Study Arms (3)

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)

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)

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)

Drug: Intranasal Modified Temozolomide

Interventions

Intranasal Modified Temozolomide DRUG

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

Also known as: Temozolomide, TMZ, IM-TMZ

Intranasal Modified Temozolomide 150 mg/M2 per day; Intranasal Modified Temozolomide 200 mg/M2 per day; Intranasal Modified Temozolomide 75 mg/M2 per day

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent signed
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Center Trials & Treatment Europe: lead

Study Sites (3)

Central Contact

Banja Luka, 78000, Bosnia and Herzegovina

Location

Central Contact

Plovdiv, 4004, Bulgaria

Location

Central Contact

Tbilisi, 0008, Georgia

Location

MeSH Terms

Conditions

Glioma; Gliosarcoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: September 8, 2019
• First Posted: September 16, 2019
• Study Start: December 20, 2019
• Primary Completion: September 21, 2022
• Study Completion: October 28, 2022
• Last Updated: April 25, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

BO (1); BU (1); GE (1)