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PreOperative Brain Irradiation in Glioblastoma (POBIG)

Primary Purpose

Glioblastoma Multiforme

Status

Recruiting

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Preoperative brain irradiation (single fraction)

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Radiotherapy, Preoperative, Neoadjuvant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

The Christie NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose or volume radiation escalation

Arm Description

Patients with a new radiological diagnosis of GBM (judged by the neuro-oncology multidisciplinary team) are to be considered for this study. This study arm will use 5 radiotherapy doses (6 Gy, 8 Gy, 10 Gy, 12 Gy and 14 Gy) and three treatment volumes (<30 cm3, 30-60 cm3 and >60 cm3). The study will use 6 dosing levels based on a combination of radiotherapy dose and treatment volume. The stepwise inclusion process allows for variation in tumour volume and location. The study will commence with dosing level 1: 8 Gy to <30 cm3 and 6 Gy to 30-60 cm3. In collaboration with the Clinical Trials Unit, the Trial Management Group will enter outcome data for patients at a given dose level into the CRM model. The model output will then guide dose escalation to determine the next dose level. After the single fraction of radiotherapy, patients will receive the standard treatment.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Registration of postoperative surgical complications.

Radiotherapy related complications

Progression free survival.

Overall survival.

Steroid dose after preoperative radiotherapy.

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.

Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis.

Full Information

NCT ID

NCT03582514

First Posted

May 30, 2018

Last Updated

August 2, 2022

Sponsor

The Christie NHS Foundation Trust

Collaborators

University of Liverpool, The Netherlands Cancer Institute, Northern Care Alliance NHS Foundation Trust, University of Manchester

1. Study Identification

Unique Protocol Identification Number

NCT03582514

Brief Title

PreOperative Brain Irradiation in Glioblastoma

Acronym

POBIG

Official Title

PreOperative Brain Irradiation in Glioblastoma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 19, 2022 (Actual)

Primary Completion Date

February 28, 2024 (Anticipated)

Study Completion Date

February 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Christie NHS Foundation Trust

Collaborators

University of Liverpool, The Netherlands Cancer Institute, Northern Care Alliance NHS Foundation Trust, University of Manchester

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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)).

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

Radiotherapy, Preoperative, Neoadjuvant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

The study uses a Continual Reassessment Method (CRM) to inform dose escalation and determine the MTD and MTIV. This is a Bayesian statistics-based model. It uses all available data from previous doses to guide dose escalation.

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose or volume radiation escalation

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Preoperative brain irradiation (single fraction)

Intervention Description

Dose and volume escalation of preoperative single-fraction radiotherapy.

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV) of single-fraction preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma

Description

Time Frame

18 months

Secondary Outcome Measure Information:

Title

Registration of postoperative surgical complications.

Time Frame

18 months

Title

Radiotherapy related complications

Time Frame

18 months

Title

Progression free survival.

Time Frame

18 months

Title

Overall survival.

Time Frame

18 months

Title

Steroid dose after preoperative radiotherapy.

Time Frame

18 months

Title

The tumor volume differences measured between the post-surgery MRI and pre-radiotherapy MRI

Description

To confirm usability of the MRI to select GBM patients for preoperative single fraction radiotherapy.

Time Frame

18 months

Title

Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis.

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gerben R Borst, MD, PhD

Phone

0161 446 3000

gerben.borst@nhs.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gerben R Borst, MD, PhD

Organizational Affiliation

The Christie NHS Foundation Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Christie NHS Foundation Trust

City

Manchester

State/Province

Greater Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gerben R Borst, MD,PhD

12. IPD Sharing Statement

Learn more about this trial

PreOperative Brain Irradiation in Glioblastoma

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