Clinical trial NCT03582514: PreOperative Brain Irradiation in Glioblastoma
Official title: PreOperative Brain Irradiation in Glioblastoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Glioblastoma Multiforme
Keywords: Radiotherapy
Preoperative
Neoadjuvant
Lead sponsor: The Christie NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Liverpool
name: The Netherlands Cancer Institute
name: Northern Care Alliance NHS Foundation Trust
name: University of Manchester
First posted: 2018-07-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV) of single-fraction preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma
timeFrame: 18 months
Secondary outcomes:
measure: Registration of postoperative surgical complications.
timeFrame: 18 months
measure: Radiotherapy related complications
timeFrame: 18 months
measure: Progression free survival.
timeFrame: 18 months
measure: Overall survival.
timeFrame: 18 months
measure: Steroid dose after preoperative radiotherapy.
timeFrame: 18 months
measure: The tumor volume differences measured between the post-surgery MRI and pre-radiotherapy MRI
timeFrame: 18 months
measure: Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis.
timeFrame: 18 months
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
Study officials:
affiliation: The Christie NHS Foundation Trust
name: Gerben R Borst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: