Clinical trial NCT06136611: Preoperative Preradiotherapy TTFields
Official title: Preoperative Preradiotherapy TTFields (PORTRAIT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Glioblastoma
Keywords: Neoadjuvant
Preoperative
Tumour Treating Fields
Lead sponsor: The Christie NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Manchester
name: Northern Care Alliance NHS Foundation Trust
name: NovoCure Ltd.
First posted: 2023-11-18
Enrollment: 42
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: PORTRAIT is a cohort study including: 14 prospective patients for the experimental arm which assumes a TRUE toxicity rate of 20% (the study needs 13 patients and we allow 1 patient for replacement). This means that there is less than 10% chance that 4 or more patients will experience a toxicity defined as a complication. For the non-experimental arm, 28 prospective patients will be recruited.
Primary purpose: TREATMENT

Brief summary: PreOperative PreRAdIotherapy Tumour Treating Fields (PORTRAIT) is a Phase I study that will test the safety and feasibility of Optune administered preoperatively and preradiotherapy in patients with a new radiological diagnosis of glioblastoma (GBM). Participants will be required to undergo additional MRI sequencing scans and provide blood, tear fluid and tissue samples over a maximum of 6 months. After the study patients will follow their standard treatment pathway.

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.

Tumour Treating Fields (TTFields), also known as Optune, is a locally applied treatment modality that has contributed to a better survival outcome for glioblastoma patients when used after surgery and chemo-radiotherapy. We hypothesize that earlier treatment using the Optune device before the surgery and between the surgery and postoperative radiotherapy can prevent REP and improve patient outcome. In this phase 1 trial, PORTRAIT (PreOpeRaTive pRerAdIotherapy Ttfields), we will test the safety and feasibility of Optune treatment before surgery and before post-operative radiotherapy in a maximum of 14 patients. Participants will be required to undergo additional MRI sequencing scans and provide blood, tear fluid and tissue samples over a maximum of 6 months.

To maximise PORTRAIT's translational and clinically relevant components, a non-experimental arm (Non-EA) of 28 patients will allow comparisons of data collected from PORTRAIT patients with comparable Standard of Care (SoC) treated patients from the same time frame.

Participants will be invited to the research study if they are over the age of 35 and have a new radiological diagnosis of glioblastoma. All recruitment and treatment will be conducted at the Christie NHS Foundation Trust and Northern Care Alliance NHS Foundation Trust.

The study is funded by a research grant from Novocure.

Eligibility criteria: Inclusion Criteria:

* Patient is aged \>35 years (age range of more likely to suffer from an IDHwt WHO grade 4 astrocytoma)\*
* Patient is male or female.
* Patient has a new radiological diagnosis of glioblastoma.
* Patient has a performance status judged by World Health Organisation, Eastern Cooperative Oncology Group \[ECOG\] score = 0-1.
* Patient 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 Optune based on available clinical information and imaging.
* PI has confirmed at the first clinic visit that study entry is clinically appropriate and safe (e.g. lack of severe and debilitating symptoms of raised intracranial pressure).
* There is intention to treat the patient with surgical resection and postoperative adjuvant therapy as per current standard of care (40Gy/15 fr or 60Gy/30fr).
* Patient has 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).
* Patient has mental capacity to consent for treatment.
* Patient is able and willing to give informed consent

Criteria specific to the experimental arm:

* Patient is able and willing to comply with study protocol requirements to continuously shave their head
* Patient is able and willing to comply with study protocol requirements to wear Optune equipment for the required duration.

Exclusion Criteria:

* Patients with uncontrolled seizures.
* Patients are due to undergo a planned biopsy procedure only.
* Patients have a suspicion of other tumour on CT body scan or known malignancy except non-melanoma skin cancer, completely resected or prostate cancer (with Prostate Specific Antigen of less than or equal to 0.1 ng/ml) within the past three years.
* Patients have contraindications to contrast-enhanced MRI scanning (e.g. claustrophobia, gadolinium allergy).

Primary outcomes:
measure: To determine the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of Pre-Operative and Pre-Radiotherapy TTFields additional to the standard treatment of care (SoC) including adjuvant TTFields.
timeFrame: 18 months
measure: To determine the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of Pre-Operative and Pre-Radiotherapy TTFields additional to the standard treatment of care (SoC) including adjuvant TTFields.
timeFrame: 18 months
Secondary outcomes:
measure: Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis
timeFrame: 18 months
measure: REP: tumour volume difference between the post-operative MRI and pre-radiotherapy MRI.
timeFrame: 18 months
measure: Registration of postoperative surgical complications
timeFrame: 18 months
measure: Registration of radiotherapy related complications
timeFrame: 18 months
measure: Steroid dose after TTFields
timeFrame: 18 months
measure: Progression free survival
timeFrame: 18 months
measure: Overall survival
timeFrame: 18 months
measure: Collection of liquid biopsies
timeFrame: 18 months
measure: Skin reactions
timeFrame: 18 month
Other outcomes:
Locations:
Study officials:
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