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

Primary Purpose

Glioma, Malignant, Gliosarcoma, Astrocytoma of Brain

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Intranasal Modified Temozolomide

About this trial

This is an interventional treatment trial for Glioma, Malignant focused on measuring TMZ, Temozolomide, Intranasal Administration, Nasal Spray, Intranasal Modified Temozolomide

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Central Contact
Central Contact
Central Contact

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

Intranasal Modified Temozolomide 75 mg/M2 per day

Intranasal Modified Temozolomide 150 mg/M2 per day

Intranasal Modified Temozolomide 200 mg/M2 per day

Arm Description

75 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

150 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

200 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)

Full Information

NCT ID

NCT04091503

First Posted

September 8, 2019

Last Updated

April 23, 2023

Sponsor

Center Trials & Treatment Europe

1. Study Identification

Unique Protocol Identification Number

NCT04091503

Brief Title

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

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Completed

Study Start Date

December 20, 2019 (Actual)

Primary Completion Date

September 21, 2022 (Actual)

Study Completion Date

October 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Center Trials & Treatment Europe

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioma, Malignant, Gliosarcoma, Astrocytoma of Brain

Keywords

TMZ, Temozolomide, Intranasal Administration, Nasal Spray, Intranasal Modified Temozolomide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intranasal Modified Temozolomide 75 mg/M2 per day

Arm Type

Active Comparator

Arm Description

75 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

Arm Title

Intranasal Modified Temozolomide 150 mg/M2 per day

Arm Type

Active Comparator

Arm Description

150 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

Arm Title

Intranasal Modified Temozolomide 200 mg/M2 per day

Arm Type

Active Comparator

Arm Description

200 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)

Intervention Type

Drug

Intervention Name(s)

Intranasal Modified Temozolomide

Other Intervention Name(s)

Temozolomide, TMZ, IM-TMZ

Intervention Description

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

Primary Outcome Measure Information:

Title

The randomized study to determine the safety of Intranasal Administration of modified Temozolomide.

Description

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.

Time Frame

up to 60 days (or withdrawal of consent or another discontinuation criterion) from date of randomization

Secondary Outcome Measure Information:

Title

The maximum tolerated therapeutic dose (MTD) of modified Temozolomide for intranasal administration

Description

Time Frame

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

Other Pre-specified Outcome Measures:

Title

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

Description

Overall survival (OS) will be determined as the time in days from the start of treatment ( randomizations day ) to death due to any cause was estimated by the Kaplan-Meier method. If it was not known for certain that the participant to die, time will be censored at the last date the participant with GBM or Gliosarcomawas known to be alive, date of magnetic resonance imaging (MRI), etc, - assessment, which will be defined as the latest among the date of the last visit.

Time Frame

180 days

Title

The effectiveness of intranasal administration of modified Temozolomide

Description

The effectiveness of the intranasal administration of modified Temozolomide will be evaluated by four MRIs with perfusion (first MRI performed one day before randomization day). The results of all MRI in dynamics will be appreciated by a consultation of radiologists.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Facility Information:

Facility Name

Central Contact

City

Banja Luka

ZIP/Postal Code

78000

Country

Bosnia and Herzegovina

Facility Name

Central Contact

City

Plovdiv,

ZIP/Postal Code

4004

Country

Bulgaria

Facility Name

Central Contact

City

Tbilisi

ZIP/Postal Code

0008

Country

Georgia

12. IPD Sharing Statement

Plan to Share IPD

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

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