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PreOperative Brain Irradiation in Glioblastoma (POBIG)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03582514
Recruitment Status : Recruiting
First Posted : July 11, 2018
Last Update Posted : August 4, 2022
Sponsor:
Collaborators:
University of Liverpool
The Netherlands Cancer Institute
Northern Care Alliance NHS Foundation Trust
University of Manchester
Information provided by (Responsible Party):
The Christie NHS Foundation Trust

Study Description
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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)).

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Radiation: Preoperative brain irradiation (single fraction) Phase 1

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: PreOperative Brain Irradiation in Glioblastoma
Actual Study Start Date : April 19, 2022
Estimated Primary Completion Date : February 28, 2024
Estimated Study Completion Date : February 28, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose or volume radiation escalation

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.

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


Outcome Measures
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Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV) of single-fraction preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma [ Time Frame: 18 months ]

    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 :
  1. Registration of postoperative surgical complications. [ Time Frame: 18 months ]
  2. Radiotherapy related complications [ Time Frame: 18 months ]
  3. Progression free survival. [ Time Frame: 18 months ]
  4. Overall survival. [ Time Frame: 18 months ]
  5. Steroid dose after preoperative radiotherapy. [ Time Frame: 18 months ]
  6. The tumor volume differences measured between the post-surgery MRI and pre-radiotherapy MRI [ Time Frame: 18 months ]
    To confirm usability of the MRI to select GBM patients for preoperative single fraction radiotherapy.

  7. Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis. [ Time Frame: 18 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03582514


Contacts
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Contact: Gerben R Borst, MD, PhD 0161 446 3000 gerben.borst@nhs.net

Locations
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United Kingdom
The Christie NHS Foundation Trust Recruiting
Manchester, Greater Manchester, United Kingdom, M20 4BX
Contact: Gerben R Borst, MD,PhD         
Sponsors and Collaborators
The Christie NHS Foundation Trust
University of Liverpool
The Netherlands Cancer Institute
Northern Care Alliance NHS Foundation Trust
University of Manchester
Investigators
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Principal Investigator: Gerben R Borst, MD, PhD The Christie NHS Foundation Trust
More Information
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Responsible Party: The Christie NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03582514    
Other Study ID Numbers: CFTSp200
21/NW/0121 ( Other Identifier: GM South Research Ethics Committee )
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: August 4, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Christie NHS Foundation Trust:
Radiotherapy
Preoperative
Neoadjuvant
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
 Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue