BIO-SHORT: Hypofractionated RT for Poor-Prognosis GBM
ConditionGlioma
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age50+
SponsorTata Memorial Centre
About this trial
High grade gliomas, particularly glioblastoma, are among the most aggressive brain tumors and are associated with poor outcomes despite standard treatment. Many patients, especially older adults or those with poor general health, are not suitable for surgery and have a life expectancy of less than 12 months. Current standard includes a shortened course of radiotherapy (over 3 weeks) combined with chemotherapy using temozolomide (TMZ), which offers limited survival benefits. This study aims to explore whether delivering radiotherapy in a shorter duration (1 or 2 weeks) at a higher dose, guided by advanced imaging with a PET scan, can improve survival in this group of patients. PET scans help identify the most active parts of the tumor, which aids in targeting of these areas more precisely, potentially improving outcomes while reducing harm to healthy brain tissue. This study will randomly assign 116 eligible patients into two groups:
* One group will receive the current standard of care (3-week radiotherapy + TMZ). * The other group will receive PET-guided radiotherapy over a shorter duration (either 5 or 10 sessions) at a higher dose, alongside TMZ.
The primary goal is to compare overall survival at one year between the two groups. The study will also assess how the disease progresses, side effects of treatment, and the impact on patients' quality of life. The study will be conducted over a total period of 6 years, including 4 years for patient enrolment and 2 years of follow-up. Participation in the study is entirely voluntary, and all patients will undergo an informed consent process. The study has been designed to follow all applicable ethical and regulatory guidelines. The results may help establish a more effective and convenient treatment option for patients with aggressive brain tumors and poor prognosis.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with biopsy proven IDH- wild type GBM or imaging defined GBM
Neurological Predictor Scale (NPS) = 2-3
Unfit for surgery and referred for direct RT
Age >/= 50 years
Disqualifiers
IDH mutant glioma
Histone altered glioma
Multifocal disease or Gliomatosis like appearance which necessitates whole brain RT
Disseminated disease in brain or spine
Trial design
Design model
Parallel
Treatments tested in this trial
Standard radiotherapy using hypofractionated RT
RadiationPatients in the standard arm will undergo target volume delineation using conventional imaging. The initial clinical target volume (CTV-initial) will include the postoperative cavity, contrast-enhancing tumor on T1-weighted MRI, and gross disease. A 1-cm isotropic expansion, edited for anatomical barriers, will generate the CTV-final to account for infiltrative spread. The planning target volume (PTV) will be created using a 3-mm geometric margin for setup uncertainty. Radiotherapy will be delivered using photon-based image-guided IMRT, prescribed to a total dose of 40 Gy in 15 fractions, administered five days per week.
Experimental Arm Intervention
RadiationPatients in the experimental arm will undergo pretreatment evaluation, MRI-based simulation, and radiotherapy delivery similar to the standard arm, with the addition of pre-treatment F-DOPA PET imaging performed according to institutional consensus protocols. Biological target volumes (BTVs) will be delineated using a tumor-to-white-matter uptake ratio \>2.0. The initial clinical target volume (CTV-initial) will include the BTV, postoperative cavity, contrast-enhancing tumor on T1-weighted MRI, and gross disease. A 1.5-cm margin, edited for anatomical barriers, will generate the CTV-final to account for infiltrative spread. The planning target volume (PTV) will be created using a 3-5-mm geometric expansion. Dose prescription will be based on PTV volume and location. Patients with PTV \>30 cc or tumors not involving the brainstem will receive 40 Gy in 10 fractions to the BTV and 35 Gy in 10 fractions to the PTV. Those with PTV ≤30 cc or brainstem involvement will receive 30 Gy in 5 frac
Treatment groups
108 Participants
are divided into 2 treatment groupsGroup A: Standard ArmActive comparator 1 intervention
Group B: Dose-escalated hypofractionated RTExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Survival Outcomes
. Overall Survival will be defined as the time elapsed from the date of randomization to date of death due to any cause.
Time frame
1 yearSecondary outcomes
1
Survival Outcome
Progression Free Survival (PFS) will be defined as the time elapsed fromthe date of randomization to the date of clinico-radiological progression or death.
Time frame
1 year2
Quality of life indices- EORTC QLQC- 30
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The scale scores are linearly transformed to a range of 0 to 100. For functional scales and global health status, higher scores indicate better quality of life; for symptom scales, higher scores indicate worse symptoms. Assessed at baseline and follow-up. Unit of Measure: Units on a scale
Time frame
Baseline / Pre-radiotherapy, 4-6 weeks post-radiotherapy, 1 month, 3 months, 6 months, 9 months, and 12 months post-radiotherapy3
Quality of life indices- EORTC BN20
Brain tumor-specific quality of life assessed using the European Organisation for Research and Treatment of Cancer Brain Neoplasm Module (EORTC QLQ-BN20). Scores are transformed to a range of 0 to 100, where higher scores indicate greater symptom burden (worse outcome). Assessed at baseline and follow-up. Unit of Measure: Units on a scale
Time frame
Baseline / Pre-radiotherapy, 4-6 weeks post-radiotherapy, 1 month, 3 months, 6 months, 9 months, and 12 months post-radiotherapy4
QTWiST (Quality of life Without Symptoms or Toxicity) calculation
QTWiST (Quality-Adjusted Time Without Symptoms or Toxicity) will be calculated by partitioning overall survival time into three mutually exclusive health states: TOX (time with treatment-related toxicity), TWiST (time without symptoms or toxicity), and REL (time after relapse/progression). The QTWiST value will be derived by applying utility weights to each health state and summing the weighted time spent in each state, expressed in months of quality-adjusted survival. Assessed at 3 months. Unit of Measure: Months (quality-adjusted survival time)
Time frame
will be done at 3 monthsSponsors and contacts
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Source ClinicalTrials.gov