BIO-SHORT: Biologically Guided Short-Course Hypofractionated RT for Poor-Prognosis GBM

NCT07338539 | Recruiting Phase 2 DMC

• 1 other identifier: 4840
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioma

Outcome Measures

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.

  1 year

Secondary Outcomes (4)

• Survival Outcome

  1 year

• Quality of life indices

  Baseline / Pre-radiotherapy, 4-6 weeks post-radiotherapy, 1 month, 3 months, 6 months, 9 months, and 12 months post-radiotherapy

• QTWiST (Quality of life Without Symptoms or Toxicity) calculation

  will be done at 3 months

• Toxicity Assessment

  Baseline / Pre-radiotherapy, 4-6 weeks post-radiotherapy, 1 month, 3 months, 6 months, 9 months, and 12 months post-radiotherapy

Study Arms (2)

Standard Arm

ACTIVE COMPARATOR

The standard arm will comprise of 3 week hypo-fractionated RT(40Gy/15#).

Radiation: Standard radiotherapy using hypofractionated RT

Dose-escalated hypofractionated RT

EXPERIMENTAL

Patients 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 fra

Radiation: Experimental Arm Intervention

Interventions

Standard radiotherapy using hypofractionated RT RADIATION

Patients 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.

Standard Arm

Experimental Arm Intervention RADIATION

Patients 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

Dose-escalated hypofractionated RT

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• IDH mutant glioma
• Histone altered glioma
• Multifocal disease or Gliomatosis like appearance which necessitates whole brain RT
• Disseminated disease in brain or spine
• NPS = 0-1 or = 4
• Karnofsky Performance Status score less than 50(Patient requires considerable assistance and frequent medical care)
• Prior administration of any systemic therapy directed against glioma (eg.Temozolomide, CCNU, Bevacizumab)

Sponsors & Collaborators

• Tata Memorial Centre: lead

Study Sites (1)

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

RECRUITING

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Abhishek Chatterjee, MD

CONTACT

2224177000; chatterji08@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will be a prospective, open-label2-arm Phase 2 randomized controlled trial with a superiority design. The standard arm will comprise of 3 week hypo-fractionated RT(40Gy/15#).The test arms will comprise of dose escalated hypo-fractionated RT (5 fractions/10 fractions). The usage of TMZ will be standard across both arms.

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: January 14, 2026
• Study Start: November 6, 2025
• Primary Completion (Estimated): October 27, 2031
• Study Completion (Estimated): October 27, 2031
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)