Clinical trial NCT05182437: Precision Radiation Treatment for Epilepsy (PRECISION)
Official title: Precision Radiation Treatment for Epilepsy (PRECISION)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Epilepsy
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
name: UMC Utrecht
name: Amsterdam University Medical Center
name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2022-01-10
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial Observational Model : Experimental Time Perspective : Prospective
Primary purpose: TREATMENT

Brief summary: The PRECISION-study offers a non-invasive, curative intervention for drug-resistant localised epilepsy patients who are not eligible for surgery. The intervention will consist of a single LINAC based SRT treatment and is given by the radiation-oncologist after detailed localisation of the epileptogenic zone with the neurologist, radiologist and neurosurgeon.

This intervention will make curative-intent treatment possible where this could otherwise not be given and is a non-invasive and non-competitive alternative to epilepsy surgery. It is expected that the health costs for this curative treatment will not exceed standard treatment, such as lifelong medication and neuromodulation.

Detailed description: In this PRECISION-study including adult patients with drug-resistant, localised epilepsy, not eligible for surgery, we offer non-invasive linear accelerator (LINAC) based Stereotactic Radiotherapy (SRT) with curative intent.

SRT and stereotactic radio-surgery (SRS) have been used to treat several types of neoplasms in the brain for several decades. Several publications (level 2 evidence) have shown the potential value of SRT in patients with drug-resistant epilepsy, however no level-1 evidence was given enabling guideline development. A recent systematic review from our institution has shown that SRT resulted in a significant seizure cure or reduction in 58% of the 170 included patients, within 2 years after treatment. Interestingly, the ROSE trial, randomising between open surgery and SRT, has demonstrated a seizure remission of 52% in the radiotherapy group after 2 years with the proportion of seizure-free patients still increasing with a longer follow-up up to 74% after 3 years. Therefore, SRT may be considered a curative treatment for drug resistant localised epilepsy. Currently, randomized controlled SRT epilepsy trials are lacking and there is a need for high quality evidence, so SRT can be clinically implemented for localised drug-resistant epilepsy patients in the Netherlands as well.

The PRECISION-study is a randomised waitlist-controlled trial in which SRT is the intervention and AED continuation and neuromodulation are the standard treatment with a 1:1 randomization. After 2-year follow up the waitlist-control group, patients are offered the intervention (optional).

We hypothesize that SRT alters the epileptogenic cerebral tissue to yield a reduction in seizures and possibly cure after 2 years, with a significant increase in the patients' quality of life.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations
3. Willingness to use contraception by a method that is deemed effective by the Investigator during the SRT treatment and for at least 30 days following the SRT therapy
4. The patient or caretaker is able to keep an epilepsy diary
5. The patient has a diagnosis of epilepsy established by a dedicated neurologist
6. The patient had at least 3 focal-onset seizures over a 3-month period despite two or more antiepileptic medication trials (according ILAE Task Force on therapeutic strategies)
7. Video electroencephalography and work-up in the epilepsy surgery working group to determine a well-circumscribed seizure focus is available
8. Evidence (e.g. 3T-MRI or a clear SEEG delineation) of the anatomic region to be targeted with SRT, correlating with the EZ hypothesis;
9. A functional MRI to lateralize language or localize visual, motor and/or sensory eloquent cortex has been performed in selected patients (if the lesion is expected to be located, based on anatomy, in the language areas).
10. The patient has completed a standard battery of neuropsychological testing
11. The patient been deemed an appropriate candidate for stereotactic radiosurgery by a dedicated Radiation Oncologist and Neurosurgeon/Epileptologist and referred for the study by one of the Dutch regional multidisciplinary epilepsy surgery working groups
12. Patients that were rejected for surgery in an earlier stage can participate in the trial if the last change of the NVS/DBS settings were more than 1 year ago or NVS/DBS was not (yet) tried.

Exclusion Criteria:

1. Pregnancy
2. If a radiation treatment plan without exceeding the constraints for the organs at risk is not feasible.
3. Prior cranial radiotherapy
4. If radiotherapy treatment is not possible for diverse reasons.
5. If the subject has clinically significant and uncontrolled major other medical condition(s) including but not limited to:

ii. psychiatric illness/social situation that would limit compliance with study requirements iii. any medical condition, with the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities iv. Progressive co-morbidity which limits overall survival.

Primary outcomes:
measure: Radiotherapy adapted Engel classification (RAEC) is I, II or III
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
Secondary outcomes:
measure: Seizure frequency
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: Seizure-free days
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: Type of epilepsy
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: EQ-5D 5 Level (EQ-5D-5L)
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: The Assessment of Quality of Life-8 Dimensions Score (AQoL-8D Score)
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: Quality of life in Epilepsy-31 Inventory (QOLIE-31)
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: 'Cost-effectiveness Resource use' is measured with iMTA Productivity Cost Questionnaire (iPCQ)
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: 'Cost-effectiveness Resource use' is measured with iMTA Medical Consumption Questionnaire (iMCQ)
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: 'Informal care' is meausured with iMTA Valuation of Informal Care Questionnaire (iVICQ)
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
measure: 'Patients' experiences' are measured with the instrument 'Patient Reported Experience Measures Medical Specialtic Care' (PREM MSZ) Medical Specialistic Care (PREM MSZ)
timeFrame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht Radiation Oncology
state: Limburg
Study officials:
affiliation: Radiation Oncologist
name: Daniëlle Eekers, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eekers DBP, Pijnappel EN, Schijns OEMG, Colon A, Hoeben A, Zindler JD, Postma AA, Hoffmann AL, Lambin P, Troost EGC. Evidence on the efficacy of primary radiosurgery or stereotactic radiotherapy for drug-resistant non-neoplastic focal epilepsy in adults: A systematic review. Seizure. 2018 Feb;55:83-92. doi: 10.1016/j.seizure.2018.01.009. Epub 2018 Jan 31.