Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04091503
Recruitment Status : Not yet recruiting
First Posted : September 16, 2019
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Center Trials & Treatment Europe

Tracking Information
First Submitted Date  ICMJE September 8, 2019
First Posted Date  ICMJE September 16, 2019
Last Update Posted Date September 17, 2019
Estimated Study Start Date  ICMJE December 10, 2019
Estimated Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2019)
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 according to the NCI CTC (5.0) with adverse events (AE) in all cohorts.
Change History Complete list of historical versions of study NCT04091503 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2019)
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 ]
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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 14, 2019)
  • Percentage of Participants Alive 6 Months After Start of Treatment of Temozolomide for intranasal administration [ Time Frame: 180 days ]
    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.
  • The effectiveness of intranasal administration of modified Temozolomide [ Time Frame: up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization ]
    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.
Original Other Pre-specified Outcome Measures
 (submitted: September 13, 2019)
  • Percentage of Participants Alive 6 Months After Start of Treatment of Temozolomide for intranasal administration [ Time Frame: 180 days ]
    Overall survival (OS) will be defined 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 was 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.
  • The effectiveness of intranasal administration of modified Temozolomide [ Time Frame: up to 90 days (or withdrawal of consent or another discontinuation criterion) from date of randomization ]
    The effectiveness of the intranasal administration of modified Temozolomide was 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.
 
Descriptive Information
Brief Title  ICMJE Evaluate the Safety and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma
Official Title  ICMJE Pilot Study to Evaluate the Safety, Tolerability and Effectiveness of Intranasal Administration of Temozolomide in Patients With Glioblastoma (Phase I)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioma, Malignant
  • Gliosarcoma
  • Astrocytoma of Brain
Intervention  ICMJE Drug: Intranasal Modified Temozolomide

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

Other Names:
  • Temozolomide
  • TMZ
  • IM-TMZ
Study Arms  ICMJE
  • Active Comparator: Intranasal Modified Temozolomide 75 mg/M2 per day
    75 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)
    Intervention: Drug: Intranasal Modified Temozolomide
  • Active Comparator: Intranasal Modified Temozolomide 150 mg/M2 per day
    150 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)
    Intervention: Drug: Intranasal Modified Temozolomide
  • Active Comparator: Intranasal Modified Temozolomide 200 mg/M2 per day
    200 mg/M2 per day Intranasal Modified Temozolomide administration of within 5 days per week (max: 30 days)
    Intervention: Drug: Intranasal Modified Temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 15, 2020
Estimated Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Silvia Hanton, Dr. +41315207002 trials@e.mail.fr
Contact: Daniel Stoyanov +33367390414 stoyanov@top-email.net
Listed Location Countries  ICMJE Bosnia and Herzegovina,   Bulgaria,   Georgia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04091503
Other Study ID Numbers  ICMJE 7SQZ309D4W
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Center Trials & Treatment Europe
Study Sponsor  ICMJE Center Trials & Treatment Europe
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Center Trials & Treatment Europe
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP