PreOperative Brain Irradiation in Glioblastoma

Glioblastoma Multiforme Clinical Trial

— POBIG  

Official title:

PreOperative Brain Irradiation in Glioblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03582514
• Other study ID #: CFTSp200
• Secondary ID: 21/NW/0121
• Status: Recruiting
• Phase: Phase 1
• Start date: April 19, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: November 2023
• Source: The Christie NHS Foundation Trust
• Contact: Gerben R Borst, MD, PhD
• Phone: 0161 446 3000
• Email: gerben.borst[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PreOperative Brain Irradiation in Glioblastoma (POBIG) is a phase I study that will test the safety and feasibility of a single fraction of preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma (GBM). After the single fraction of radiotherapy, patients will receive standard treatment. The standard treatment consists of resection of the tumor followed by (chemo)radiation (i.e. radiotherapy +/- daily temozolomide (75mg/m2) for 6 weeks (60Gy/30fr) or for 3 weeks (40Gy/15fr)).

Description:

Glioblastoma is the most common primary malignant brain tumour in adults. Its outcomes are poor due to local disease progression in most patients. Current treatment includes surgery followed by chemotherapy and radiotherapy 4-6 weeks after surgery. In this time interval, some tumour cells do not receive any treatment. Furthermore, studies show that around half of all glioblastoma patients experience rapid early progression (REP) i.e. growth of the tumour in the time interval between surgery and postoperative chemotherapy/radiotherapy. REP is associated with a shorter survival and there are currently no effective treatments or preventative measures to address it. Radiotherapy delivered earlier before the operation could prevent REP and improve patient outcome. In this phase I study - PreOperative Brain Irradiation in Glioblastoma (POBIG), we will test the safety and feasibility of giving a single dose (fraction) of radiotherapy before surgery in patients with a new radiological diagnosis of glioblastoma. This study will be a dose escalation study to determine the maximum tolerated dose of preoperative radiotherapy and maximum volume of tumour that can be safely irradiated preoperatively. We hypothesise that preoperative radiotherapy will reduce the rate of REP and improve patient outcome.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years.

• Male or female.

• New radiological diagnosis of glioblastoma.

• Performance status judged by World Health Organisation, Eastern Cooperative Oncology Group [ECOG] score = 0-1.

• Case has been reviewed by Neuro-oncology multidisciplinary team (MDT - neurosurgeon, clinical oncologist, radiologist and pathologist); MDT consensus that offering study entry is clinically appropriate and safe i.e. patient unlikely to come to harm (e.g. hydrocephalus) from delayed surgery and pre-operative radiotherapy based on available clinical information and imaging.

• Confirmation at first clinic visit that study entry is clinically appropriate and safe (e.g. lack of severe and debilitating symptoms of raised intracranial pressure).

• Intention to treat with surgical resection and postoperative adjuvant therapy as per current standard of care (Stupp regimen).

• Tumour size, location and configuration meet radiotherapy treatment planning criteria (e.g. to secure cold spot/hot spot, meets dose constraints for organs at risk when accounting for post-operative radiotherapy).

• Adequate haematological and biochemical parameters for surgery and contrast agent administration (full blood count and coagulation profile deemed acceptable by clinical team, eGFR >30ml/min).

• Mental capacity to consent for treatment.

• Able and willing to give informed consent.

Exclusion Criteria:

• Planned biopsy procedure only.

• Suspicion of other tumour on CT body scan or known malignancy except non-melanoma skin cancer, completely resected cervical or prostate cancer (with Prostate Specific Antigen of less than or equal to 0.1 ng/ml) within the past 3 years.

• Contraindications to contrast-enhanced MRI scanning (e.g. claustrophobia, gadolinium allergy).

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Radiation:
• Preoperative brain irradiation (single fraction)
Dose and volume escalation of preoperative single-fraction radiotherapy.

Locations

Country	Name	City	State
United Kingdom	The Christie NHS Foundation Trust	Manchester	Greater Manchester

Sponsors (5)

Lead Sponsor	Collaborator
The Christie NHS Foundation Trust	Northern Care Alliance NHS Foundation Trust, The Netherlands Cancer Institute, University of Liverpool, University of Manchester

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV) of single-fraction preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma	These will be determined by the following dose limiting complications: Radiotherapy related swelling leading to a change of the scheduled date of surgery.; Post-operative radiotherapy commencement delayed to beyond 6 weeks after surgery due to radiation related symptoms and/or complications from surgery.; Interruption of post-operative radiotherapy >5 days.	18 months
Secondary	Registration of postoperative surgical complications.		18 months
Secondary	Radiotherapy related complications		18 months
Secondary	Progression free survival.		18 months
Secondary	Overall survival.		18 months
Secondary	Steroid dose after preoperative radiotherapy.		18 months
Secondary	The tumor volume differences measured between the post-surgery MRI and pre-radiotherapy MRI	To confirm usability of the MRI to select GBM patients for preoperative single fraction radiotherapy.	18 months
Secondary	Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis.		18 months