First-In Man (FIM) Study MR-Linac

Study Overview
=================
Brief Summary
-----------------
Investigational device is the Magnetic resonance imager linear accelerator. Five (5) patients with bone metastases will be treated with palliative intention in this study. The goal is to confirm the pre-clinically demonstrated technical accuracy and safety of the newly developed MR-Linac in the clinical setting.

Detailed Description
-----------------
This is a single center prospective proof of concept study including accuracy and safety aspects according to R-IDEAL stage 1 criteria. Five (5) patients with bone metastases will be treated with palliative intention in this study. Treatment will consist of a single fraction. The MR linear accelerator (MRL) integrates a radiotherapy accelerator and a diagnostic quality 1.5T MRI, enabling soft-tissue visualization during the actual radiation delivery for improved targeting. This enables on-line treatment optimization for precise radiation delivery. Better visualization of the tumour targets and the surrounding healthy tissues, at the exact moment of treatment, makes it possible to adapt the dose to the actual anatomy while optimally sparing normal tissues.

Official Title
-----------------
First-In Man (FIM) Study MR-Linac

Conditions
-----------------
Bone Metastases

Intervention / Treatment
-----------------
* Device: Magnetic resonance imager linear accelerator


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: In order to be eligible to participate in this study, a patient must meet all of the following criteria: Painful bone metastases in the lumbar spine Radiographic evidence of bone metastases Histologic proof of malignancy (primary carcinoma) Karnofsky Performance Score ≥ 50 Age ≥ 18 years Able to provide written informed consent Exclusion Criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: Prior radiation therapy within the region planned to be irradiated Contraindication for MRI according to screening protocol radiology department UMCU (e.g. cardiac pacemakers, and defibrillators, artificial heart valves or cochlear implants, https://richtlijn.mijnumc.nl/Beeld/MRI/Paginas/MRI-Veiligheid-Contra-indicaties.aspx Claustrophobia Standard systemic anti-cancer therapy or radionuclide therapy within 48 hours before or after treatment. Any other type of not standard systemic anti-cancer treatment, except for endocrine treatment. Unstable spine requiring surgical stabilization Neurological deficit due to bone metastasis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Proof of concept including accuracy and safety aspects according to R-IDEAL stage 1 criteria
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment arm<br>Single arm study, 5 patient with bone metastasis will be enrolled for palliative treatment with the Magnetic resonance imager linear accelerator (MR-Linac). | Device: Magnetic resonance imager linear accelerator<br>* The MR linear accelerator (MRL) integrates a radiotherapy accelerator and a diagnostic quality 1.5T MRI, enabling soft-tissue visualization during the actual radiation delivery for improved targeting. This enables on-line treatment optimization for precise radiation delivery. Better visualization of the tumour targets and the surrounding healthy tissues, at the exact moment of treatment, makes it possible to adapt the dose to the actual anatomy while optimally sparing normal tissues.<br>* Other names: Unity;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the treatment system (a dose distribution accuracy ≤ 5% will be considered acceptable). Incidence of acute toxicity (CTCAE grade 2 are higher) and incidence of Serious (unexpected) Adverse Events will be measured. | Safety of the system: System behaves in accordance with the workflow and risk mitigation plan, Dosimetric safety: An independent dosimetry check before start irradiation (Oncentra) and an independent dosimetry during irradiation (second chamber) will be used. For the overall process a dose distribution accuracy ≤ 5% will be considered acceptable. Patients safety: by reporting any acute toxicity > grade 2 (according CTCAE version 4.0 for acute toxicity) and any Serious (Unexpected) Adverse Events (S(U)AE) within 12 weeks after treatment | During treatment (Day 0). For patient safety patients will be contacted at day 1, week 2 and week 12 after treatment. | 
| Geometrical accuracy of targeting by online MR imaging | Geometrical accuracy: will be checked online by using the MRI in combination with VolumeTool visualization and off-line by comparison of the EPID beam data with the prescribed beam data. A positioning error of ≤ 5 mm will be considered acceptable | During treatment (day 0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive analysis of the clinical workflow by keeping a log book for the entire procedure. | Feasibility of the clinical workflow: by keeping a log book for the entire procedure. The validation of radiation delivery includes assessing the hardware performance and the See-Plan-Treat work flow for on-line MRI guided adaptive radiotherapy. | During treatment (day 0) | 
| Patients comfort | Patient comfort during the MR-Linac treatment: by patient questionnaire. | immediately after treatment (day 0) |