Comparing the effect of neoadjuvant temozolomide before chemoradiotherapy with chemoradiotherapy followed by adjuvant temozolomide on progression free survival in patients with Glioblastoma
Discovering a method to improve progression free survival (PFS) and overall survival (OS) and cognitive complications in glioblastoma patients
Design
A randomized phase 3 clinical trial with parallel groups design of 134 patients, enrolled between October 2020 and July 2023 in a single center and followed for 2 years
Settings and conduct
Patients referred to cancer institute of Tehran Imam Khomeini hospital who have the inclusion criteria would be enrolled in this trial after being informed and randomized in either control or interventional arm. There is no possibility of blinding categorization.
Participants/Inclusion and exclusion criteria
Patients aged between 18-80 years old with histopathologic proven primary glioblastoma who are candidate for chemoradiotherapy and have acceptable performance status
Intervention groups
1.The control group would receive conventional radiotherapy and temozolomide 60 Gy radiotherapy is administered in 30 fractions over 6 weeks, concomitantly with daily doses of temozolomide 75 mg/m2 followed by 6 cycles of adjuvant temozolomide dosage 200 mg/m2 days 1-5 in a 28 days schedule
2. The intervention group receive neoadjuvant temozolomide 3 cycles followed by chemoradiotherapy and then 3 cycles of temozolomide . If clinical symptoms and signs of progression is noted radiotherapy is initiated immediately. Radiotherapy and chemotherapy are administered in the same way as for the standard treatment arm.(GTV=post-op MRI axial T1 +contrast and tumor bed, CTV=GTV+2cm smart margin)
Follow up for both treatment arms is 48 months after end of treatment
Main outcome variables
Comparing progression free survival, symptoms, overall survival, clinical response due to imaging, acute reactions, cognitive function
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150929024266N5
Registration date:2020-11-30, 1399/09/10
Registration timing:registered_while_recruiting
Last update:2020-11-30, 1399/09/10
Update count:0
Registration date
2020-11-30, 1399/09/10
Registrant information
Name
Reza Ghalehtaki
Name of organization / entity
Tehran University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 6119 2520
Email address
r-ghaletaki@student.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-10-06, 1399/07/15
Expected recruitment end date
2026-02-21, 1404/12/02
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparing the effect of neoadjuvant temozolomide before chemoradiotherapy with chemoradiotherapy followed by adjuvant temozolomide on progression free survival in patients with Glioblastoma
Public title
Role of initiating treatment with temozolomide in Glioblastoma
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Histologically proven glioblastoma grade IV: GBM
Age 18 - 80 years old
Performance status WHO 0-2
Men and women of child bearing potential must be using adequate contraception
Normal organ function, except if abnormal due to tumor involvement Patient
Exclusion criteria:
Prior chemotherapy or radiotherapy for malignant glioma
Any other active malignancies within the last 5 years, except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ
Pregnancy or breast feeding
Any condition (medical, social, psychological) which would prevent adequate information and follow up
Platelet count (TPK) <100 x 10^9/L
Hemoglobin (Hb) < 90 g/L
Neutrophils: < 1.5 x 10^3/mm3 or LPK < 3.0 x 10^9/L
Serum creatinine and bilirubin > 1.5 times the upper limit of normal (ULN)
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) >3 x ULN
Age
From 18 years old to 80 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
134
Randomization (investigator's opinion)
Randomized
Randomization description
patients were randomized into two groups by table of random numbers
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Tehran University of Tehran
Street address
Keshavarz Blvd. Gharib St. Imam Khomeini Hospital Complex, Cancer institute
City
Tehran
Province
Tehran
Postal code
1419733141
Approval date
2020-10-06, 1399/07/15
Ethics committee reference number
IR.TUMS.IKHC.REC.1399.240
Health conditions studied
1
Description of health condition studied
Glioblastoma
ICD-10 code
C71
ICD-10 code description
Malignant neoplasm of brain
Primary outcomes
1
Description
Progression free survival
Timepoint
first MRI done 2-8 weeks after treatment and then within every 2-4 months interval for 3 years, every 3-6months after that, if any clinical symptoms presents follow out would take place in shorter intervals
Method of measurement
MRI Imaging changes
Secondary outcomes
1
Description
Cognitive changes
Timepoint
Before initiating treatment and then after completion of each therapeutic modality, 3 times for the control group and 4 times for the intervention group
Method of measurement
MMS (Mini-Mental State) examination test
2
Description
Hematologic complications
Timepoint
Weekly during radiotherapy and before initiation each cycle of chemotherapy
Method of measurement
Lab tests CBC
3
Description
Overall survival (OS)
Timepoint
The date of the start of treatment until the time that patients are still alive
Method of measurement
time monthly
4
Description
Renal complications
Timepoint
Weekly during radiotherapy and before initiation each cycle of chemotherapy
Method of measurement
Lab tests BUN, Cr
5
Description
Hepatic complications
Timepoint
Weekly during radiotherapy and before initiation each cycle of chemotherapy
Method of measurement
Lab tests AST, ALT, ALKP
6
Description
Neurologic defects
Timepoint
Weekly during radiotherapy and before initiation each cycle of chemotherapy
Method of measurement
Weekly history taking presence or absence of seizure, headache, FND(focal neurological defect), dexamethasone usage
Intervention groups
1
Description
Neoadjuvant temozolomide 3 cycles 200 mg/m2 days 1-5 in a 28 days schedule, followed by chemoradiotherapy , 60 Gy radiotherapy single phase is administered in 2 Gy fractions over 6 weeks (GTV=post-op MRI axial T1 +contrast tumor bed ,CTV=GTV+2cm smart margin), concomitantly with daily doses of temozolomide 75 mg/m2 and then 3 cycles of temozolomide dosage 200 mg/m2 days 1-5 in a 28 days schedule. If clinical symptoms and signs of progression is noted radiotherapy is initiated immediately.
Category
Treatment - Other
2
Description
Control group: Chemoradiotherapy, 60 Gy radiotherapy single phase is administered in 2 Gy fractions over 6 weeks (GTV=post-op MRI axial T1 +contrast and tumor bed, CTV=GTV+2cm smart margin), concomitantly with daily doses of temozolomide 75 mg/m2 6 followed by 6 cycles of temozolomide dosage 200 mg/m2 days 1-5 in a 28 days schedule.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini Hospital Complex, cancer institute
Full name of responsible person
Reza Ghaletaki
Street address
Keshavarz Blvd. Gharib St. Imam Khomeini Hospital Complex, Cancer institute
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119 2585
Fax
+98 21 6658 1604
Email
isnr.group@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Mohammad Ali Sahraeian
Street address
No 206, First Floor, Official Building, Medical Faculty, Poursina Street, 16th Azar Street, Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 8145 5618
Email
research@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
No
Title of funding source
Deputy of Research, Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Reza Ghalehtaki
Position
Assisstant Professor
Latest degree
Specialist
Other areas of specialty/work
Radiotherapy
Street address
Imam Khomeini Hospital Complex, Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1461833359
Phone
+98 21 6119 2585
Email
rghalehtaki@tums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Reza Ghalehtaki
Position
َAssistant Professor
Latest degree
Specialist
Other areas of specialty/work
Radiotherapy
Street address
Imam Khomeini Hospital Complex, Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1461833359
Phone
+98 21 6119 2585
Email
rghalehtaki@tums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Department of Radiation Oncology, Tehran University of Medical Sciences
Full name of responsible person
Reza Ghalehtaki
Position
Assistant professor
Latest degree
Specialist
Other areas of specialty/work
Radiotherapy
Street address
Department of Radiation Oncology, Cancer Institute, Imam Khomeini Hospital, Keshavarz Blvd
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119 2585
Fax
Email
Rezaght@gmail.com
Web page address
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
The study protocol (complete), Informed consent (only the blank template), Clinical study report (as the published article)
When the data will become available and for how long
6 month after the end of the study
To whom data/document is available
Only to academic individuals.
Under which criteria data/document could be used
The written request is mandatory by email emphasizing the mentioning of study conductors in case of using data
From where data/document is obtainable
By contacting this email address: rezaght@gmail.com
What processes are involved for a request to access data/document
The study conductors will evaluate each request due to applicants' CV and scientific portfolio. The requests will be responded by 1 month after receiving an email.