Phase II Trial of Neo-adjuvant Temozolomide Prior to Combined Temozolomide and Concurrent Accelerated Hypofractionated External Beam Radiotherapy Followed by Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme

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ClinicalTrials.gov Identifier: NCT01702610

Recruitment Status : Completed

First Posted : October 8, 2012

Last Update Posted : September 28, 2016

Sponsor:

Information provided by (Responsible Party):

George Shenouda, McGill University Health Center

Study Description

Brief Summary:

Patients with GBM, who were deemed ineligible for any active protocols at our centre, received accelerated hypofractionation EBRT if 60Gy/20Fx using an IMRT technique with conventional dose of concomitant and adjuvant TMX as per the STUPP's TMZ schedule. Thirty five patients, 15 females and 20 males with a median age of 63 (range 31-78) were treated with a median KPS of 90 (range 50-100). Four patients had multicentric disease at presentation. Eight patients had biopsy only while the rest had a near total resection (n=14) and partial resection (n=13) with a median follow-up of 12.1 months, the median survival was 14.4 months.

Condition or disease	Intervention/treatment	Phase
Glioblastoma Mutliforme	Radiation: IMRT Technique Radiation: IMRT and accelerated hypofractionation technique Radiation: neo-adjuvant TMZ followed by accelerated hypofractionated EBRT Drug: Temozolomide and Accelerated Hypofractionation RT	Not Applicable

Detailed Description:

In this proposal, the total cumulative dose of TMZ is unchanged as compared to the doses used in the Stupp protocol. In this proposal, the dose of TMZ is the same, with the sole difference that TMZ will be given in a neo-adjuvant setting for two weeks and then continued at the same dose concurrently with the accelerated hypofractionated EBRT delivering 60Gy in 4 weeks. The adjuvant component of TMZ remains unchanged from current standard practice.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	50 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Study Start Date :	December 2008
Actual Primary Completion Date :	December 2014
Actual Study Completion Date :	December 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Temozolomide

Genetic and Rare Diseases Information Center resources: Glioblastoma Glioma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Temozolomide, Accelerated Hypofractionated RT Patient will receive two weeks of neo-adjuvant Temozolomide followed by Accelerated Hypofractionated RT for a total of 20 fractions for a total of 60Gy followed by Temozolomide for 12 cycles.	Radiation: IMRT Technique Radiation: IMRT and accelerated hypofractionation technique Intervention is the technique and accelerated fractionation used to treat GBM Radiation: neo-adjuvant TMZ followed by accelerated hypofractionated EBRT Two weeks of neo-adjuvant TMZ followed by XRT+TMX followed by TMZ as adjuvant component Drug: Temozolomide and Accelerated Hypofractionation RT

Outcome Measures

Primary Outcome Measures :

Percent of patients completing the study treatment [ Time Frame: At one year ]
To determine overall survival.
To assess toxicity of the regimen [ Time Frame: At one year ]
Toxicity will be assessed and graded according to CTCAE-V3

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age: 18 years or older
Histological confirmation of supratentorial GBM
KPS > 60
Neurological function 0 or 1
Adequate bone marrow as defined below:
absolute neutrophil count (ANC) > 1500 cells/mm3
platelets > 100,000 cells/mm3
hemoglobin > 10g/dl
Adequate renal function as defined below:
BUN < 25mg/dl within 14 days prior to study registration
creatinine of 63 to 103 umol/L within 14 days prior to study registration
Adequate hepatic function as defined below:
Bilirubin of 3 to 21 umol/L within 14 days prior to study registration
ALT & AST < 3xnormal range within 14 days prior to study registration
Neoadjuvant TMZ to start within 3 weeks of surgery/biopsy if no resection was deemed feasible
A diagnostic contrast-enhanced MRI or CT scan of the brain must be performed preoperatively and postoperatively.
History, physical and neurological examination within 14 days prior to study registration.
For females of child-bearing potential, negative pregnancy test within 72 hours prior to starting TMZ.
Able to sign an informed study-specific consent

Exclusion Criteria:

Margin of contrast-enhanced residual mass closer than 15mm from the optic chiasm or optic nerves.
Prior invasive malignancy, unless disease-free for >3years
Recurrent or multifocal GBM
Severe co-morbidities such as
unstable angina
transmural myocardial infarction within 6 months
COPD at the time of registration
Hepatic insufficiency
Bacterial or fungal infection requiring IV antibiotics at the time of registration
Acquired Immune Deficiency Syndrome (AIDS)
Major medical illnesses or psychiatric impairments
Pregnant women or lactating women

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01702610

Locations


Canada, Quebec
McGill University Health Center
Montreal, Quebec, Canada, H3G 1A4

Sponsors and Collaborators

McGill University Health Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shenouda G, Souhami L, Petrecca K, Owen S, Panet-Raymond V, Guiot MC, Corredor AG, Abdulkarim B. A Phase 2 Trial of Neoadjuvant Temozolomide Followed by Hypofractionated Accelerated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Patients With Glioblastoma. Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):487-494. doi: 10.1016/j.ijrobp.2016.11.006. Epub 2016 Nov 15.


Responsible Party:	George Shenouda, Principal Investigator, McGill University Health Center
ClinicalTrials.gov Identifier:	NCT01702610 History of Changes
Other Study ID Numbers:	GEN-08-013 MGRT01:TMZ/GBM ( Other Identifier: McGill University Health Center )
First Posted:	October 8, 2012 Key Record Dates
Last Update Posted:	September 28, 2016
Last Verified:	September 2016

Additional relevant MeSH terms:


Glioblastoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms	Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Temozolomide Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

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