Short Course Chemo-Radiation Therapy for Patients With Newly Diagnosed Glioblastoma: Comparison of Two Established Schedules
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Overall survival (OS)
Study Overview
Brief Summary
This is a prospective, randomized, open-label, exploratory trial of temozolomide-based chemo-radiotherapy which compares two widely used established radiation schedules with either 40 Gy in 15 fractions or 25 Gy in 5 fractions with concurrent temozolomide for both schedules in patients with glioblastoma.
Detailed Description
All patients in the study will receive usual care with short-course radiotherapy (RT) and TMZ-chemo pills.
There are three phases of treatment in this study: the Chemo-radiation Phase, the Adjuvant Phase, and the Follow-Up Phase.
Twenty-eight or fewer days prior to starting the Chemo-radiation Phase, patients will have a baseline Magnetic Resonance Imaging (MRI) scan.
Chemo-radiation Phase: In this, patient will be assigned to either a one week or a three week treatment group with radiation treatments given approximately 5 days a week as directed by the study doctor. During this time they will also take TMZ-chemo orally (by mouth) once a day on every evening including weekends starting the evening of the day that you start radiotherapy. Once radiation is completed, you will stop taking TMZ-chemo for approximately 4 weeks before going to the next phase.
Radiation therapy: Patients will be randomized between standard radiation treatment at UPMC Radiation Oncology facilities included in this protocol with either 40 Gy in 15 fractions or 25 Gy in 5 fractions, using 6 to 23 MV x-rays along with concurrent temozolomide chemotherapy for both treatment schedules.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Each patient must meet all of the following inclusion criteria for study enrollment:
- •Age ≥18 with ability to provide written informed consent
- •Pathologically confirmed WHO Grade IV Gliobastoma prior receiving radiotherapy
- •Prior radiotherapy to a dose of ≥50Gy
- •No signs of distant metastases
- •Baseline laboratory assessment including CBC and blood chemistry, ANC > or equal 1500, Platelet count greater or equal
- •Liver function tests and creatinine not greater than twice ULN.
- •Patient should not be pregnant. Urine or blood β-HCG within 14 days prior to study start for females who are not atleast one year post-menopausal or who have ot undergone a surgical sterilization procedure
- •A baseline MRI scan of the brain is required to determine how much tumor is present for properly planning patient's radiotherapy.
- •Karnofsky Performance Status (KPS) below 60 or ECOG of 3 or 4
- •Any number or type of prior chemotherapy is allowed (patient may receive concurrent or adjuvant systemic therapy such as cetuximab at the discretion of the treating oncologic team).
Exclusion Criteria
- •Patients meeting any of the following exclusion criteria are not eligible for enrollment:
- •Evidence of distant metastases on any staging or imaging modality
- •Women who are breast feeding, or have a positive pregnancy test (reproductive age should use effective birth control during study)
- •Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the principal investigator.
- •Karnofsky Performance Status less than 50
- •Prior radiotherapy to involved site in brain.
Arms & Interventions
40 Gy in 15 fractions
Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m^2 temozolomide per day for 15 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.
Intervention: Radiation Therapy (Radiation)
40 Gy in 15 fractions
Patients randomized to 40 Gy in 15 fractions will receive 75 mg/m^2 temozolomide per day for 15 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.
Intervention: Temozolomide Oral Product (Drug)
25 Gy in 5 fractions
Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 temozolomide per day for 5 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.
Intervention: Radiation Therapy (Radiation)
25 Gy in 5 fractions
Patients randomized to 25 Gy in 5 fractions will receive 150 mg/m^2 temozolomide per day for 5 days starting the first day of radiotherapy. This treatment will be followed by standard monthly 5 day cycles at 150 mg/m^2 for upto 1 year.
Intervention: Temozolomide Oral Product (Drug)
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: Up to 9 years
The length of time from the start of treatment that patients remain alive.
Change in Absolute Lymphocyte Count
Time Frame: From baseline up to 5 years.
Differences in absolute lymphocyte count (total lymphocyte count \<800 - 500/mm\^3 \<0.8 - 0.5 x 10\^9 /L) / total # patients, during treatment.
Secondary Outcomes
- Progression free survival (PFS) - 25 Gy in 5 fractions(Up to 9 years)
- Progression free survival (PFS) - 40 Gy in 15 fractions(Up to 9 years)
Investigators
John Flickinger
Professor of Radiation Oncology & Neurosurgery
University of Pittsburgh