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

NCT ID: NCT01702610

Last Updated: 2016-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2014-12-31

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.

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.

Conditions

Glioblastoma Mutliforme

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

IMRT Technique

Intervention Type: RADIATION

IMRT and accelerated hypofractionation technique

Intervention Type: RADIATION

Intervention is the technique and accelerated fractionation used to treat GBM

neo-adjuvant TMZ followed by accelerated hypofractionated EBRT

Intervention Type: RADIATION

Two weeks of neo-adjuvant TMZ followed by XRT+TMX followed by TMZ as adjuvant component

Temozolomide and Accelerated Hypofractionation RT

Intervention Type: DRUG

Interventions

IMRT Technique

Intervention Type: RADIATION

IMRT and accelerated hypofractionation technique

Intervention is the technique and accelerated fractionation used to treat GBM

Intervention Type: 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

Intervention Type: RADIATION

Temozolomide and Accelerated Hypofractionation RT

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

George Shenouda

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

McGill University Health Center

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 28011051 (View on PubMed)

Other Identifiers

MGRT01:TMZ/GBM

Identifier Type: OTHER

Identifier Source: secondary_id

GEN-08-013

Identifier Type: -

Identifier Source: org_study_id