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

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.

Study Overview

• Status: Completed
• Conditions: Bone Metastases
• Intervention / Treatment: Device: Magnetic resonance imager linear accelerator

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Centre Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment arm; 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; 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.; Other Names: MR-Linac; 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)

Collaborators and Investigators

• Sponsor: Nucletron Operations BV
• Collaborators: Factory CRO for Medical Devices B.V.
• Investigators: Principal Investigator: Ina Jürgenliemk-Schulz, MD, PhD, UMCU

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): July 11, 2017
• Study Completion (Actual): September 8, 2017

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 15, 2017

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 27, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: MR-Linac-CIP-001 Version 2.0; NL60984.041.17 (Other Identifier: CCMO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No