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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
George Shenouda, McGill University Health Center
ClinicalTrials.gov Identifier:
NCT01702610
First received: August 22, 2012
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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 Intervention
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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Percent of patients completing the study treatment [ Time Frame: At one year ] [ Designated as safety issue: No ]
    To determine overall survival.

  • To assess toxicity of the regimen [ Time Frame: At one year ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed and graded according to CTCAE-V3


Estimated Enrollment: 40
Study Start Date: December 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01702610

Locations
Canada, Quebec
McGill University Health Center
Montreal, Quebec, Canada, H3G 1A4
Sponsors and Collaborators
McGill University Health Center
  More Information

No publications provided

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
Study First Received: August 22, 2012
Last Updated: June 3, 2014
Health Authority: Canada: Health Canada Therapeutic Products Directorate

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
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014