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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

Primary Purpose

Glioblastoma Mutliforme

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

IMRT Technique

IMRT and accelerated hypofractionation technique

neo-adjuvant TMZ followed by accelerated hypofractionated EBRT

Temozolomide and Accelerated Hypofractionation RT

About this trial

This is an interventional treatment trial for Glioblastoma Mutliforme

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

McGill University Health Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temozolomide, Accelerated Hypofractionated RT

Arm Description

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.

Outcomes

Primary Outcome Measures

Percent of patients completing the study treatment

To determine overall survival.

To assess toxicity of the regimen

Toxicity will be assessed and graded according to CTCAE-V3

Secondary Outcome Measures

Full Information

NCT ID

NCT01702610

First Posted

August 22, 2012

Last Updated

September 26, 2016

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT01702610

Brief Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

December 2008 (undefined)

Primary Completion Date

December 2014 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

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

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

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

Glioblastoma Mutliforme

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Temozolomide, Accelerated Hypofractionated RT

Arm Type

Experimental

Arm Description

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.

Intervention Type

Radiation

Intervention Name(s)

IMRT Technique

Intervention Type

Radiation

Intervention Name(s)

IMRT and accelerated hypofractionation technique

Intervention Description

Intervention is the technique and accelerated fractionation used to treat GBM

Intervention Type

Radiation

Intervention Name(s)

neo-adjuvant TMZ followed by accelerated hypofractionated EBRT

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Temozolomide and Accelerated Hypofractionation RT

Primary Outcome Measure Information:

Title

Percent of patients completing the study treatment

Description

To determine overall survival.

Time Frame

At one year

Title

To assess toxicity of the regimen

Description

Toxicity will be assessed and graded according to CTCAE-V3

Time Frame

At one year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Facility Information:

Facility Name

McGill University Health Center

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3G 1A4

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

28011051

Citation

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.

Results Reference

derived

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