PreOperative Brain Irradiation in Glioblastoma

NCT03582514 | Unknown Phase 1 DMC

• 2 other identifiers: CFTSp20021/NW/0121
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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)).

Conditions

Glioblastoma Multiforme

Keywords

Radiotherapy; Preoperative; Neoadjuvant

Outcome Measures

Primary Outcomes (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

  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 Outcomes (7)

• Registration of postoperative surgical complications.

  18 months

• Radiotherapy related complications

  18 months

• Progression free survival.

  18 months

• Overall survival.

  18 months

• Steroid dose after preoperative radiotherapy.

  18 months

Study Arms (1)

Dose or volume radiation escalation

EXPERIMENTAL

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)

Interventions

Preoperative brain irradiation (single fraction) RADIATION

Dose and volume escalation of preoperative single-fraction radiotherapy.

Dose or volume radiation escalation

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• University of Liverpool: collaborator
• The Netherlands Cancer Institute: collaborator
• Northern Care Alliance NHS Foundation Trust: collaborator
• University of Manchester: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

RECRUITING

Related Publications (1)

• Waqar M, Roncaroli F, Djoukhadar I, Akkari L, O'Leary C, Hewitt L, Forte G, Jackson R, Hessen E, Withington L, Beasley W, Richardson J, Golby C, Whitehurst P, Colaco R, Bailey M, Karabatsou K, D'Urso PI, McBain C, Coope DJ, Borst GR. Study protocol: PreOperative Brain Irradiation in Glioblastoma (POBIG) - A phase I trial. Clin Transl Radiat Oncol. 2023 Jan 18;39:100585. doi: 10.1016/j.ctro.2023.100585. eCollection 2023 Mar.

  PMID: 36845633 DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Gerben R Borst, MD, PhD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gerben R Borst, MD, PhD

CONTACT

0161 446 3000; gerben.borst@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 30, 2018
• First Posted: July 11, 2018
• Study Start: April 19, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

GB (1)