Northern Alberta Linac-MR Image-Guided Radiotherapy (Northern LIGHTs-2)

Study Overview
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Brief Summary
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Cancers are often treated with external beam radiotherapy. Current radiotherapy treatments are performed using computed tomography (also known as CT) scans which may not always clearly identify the cancer. In some instances, magnetic resonance imaging (MRI) may be able to better identify cancers. Therefore, efforts are currently underway to use the MRI scans to improve radiotherapy treatments or eventually even use radiotherapy equipment that only uses MRI scans to guide treatments. This new technology that will only use MRI scans to guide treatments is called the Linac-MR (linear accelerator with an MRI). This new Linac-MR is a unique innovation at the Cross Cancer Institute, with theoretical advantages over other Linac-MR machines that are being tested elsewhere in the world. This feasibility study is being done as a first step in clinical development of the Linac-MR, as this new technology has to be tested to see if it is acceptable to both doctors and participants. The purpose of this Phase I/II study is (1) to verify treatment completion as intended and scheduled the oncology team, and (2) to evaluate treatment effects, including any expected or unexpected radiation side effects and cancer response to radiation. This study will allow the researchers at the Cross Cancer Institute to develop this technology further by conducting additional studies to take advantage of MRI scanning on tumor tracking during radiation treatments.

Detailed Description
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This prospective, open-label, Phase I/II, clinical trial is feasibility study to evaluate MR-guided radiotherapy with the Alberta linac-MR P3 system in adult patients with cancer that are treated with external beam radiotherapy in four graduated stages (described below), progressing from palliative participants with simple techniques to curative participants with complex techniques, with progression to each stage determined by an internal SAFE review committee. Conventional treatment margins and doses will be utilized, with the MR being utilized in place of CT based imaging. The intent is to replicate current CT based treatments on the Alberta linac-MR P3 system using MR guided imaging, planning and treatment delivery. MR imaging will be utilized for simulation, planning and image guidance. Dosimetry will be done as per standard of care. MRI contrast may be used, as applicable. Adverse events will be collected weekly during RT, and participants will complete one questionnaire at the end of their RT treatment. Follow-up will consist of adverse event assessment at 1, 3, 6, and 12 months following completion of RT, and may be assessed annually via chart review for up to 5 years. Survival status will be assessed at 12 months following completion of RT, and then annually for up to 5 years. In stage 1, 10 to 28 participants with incurable malignancies that require palliative radiotherapy with parallel-opposed pair beam arrangements will be enrolled. These will be patients with bone or brain metastases from their malignancies that require either a single fraction or multiple fractions of radiotherapy. The treatment will be a simple opposed pair beam arrangement to a dose of a single 8 Gy or to a dose of 20 Gy over a course of 5 fractions. Once some initial treatments are completed, and at the discretion of an internal SAFE review committee, additional treatment sites will be permitted (i.e. lung, abdomen, etc.) that are also utilizing a simple opposed pair beam arrangement with the above doses. In stage 2, 10 to 28 participants with malignancies (curative or palliative treatments) that require multi-field arrangement for their external beam radiotherapy will be enrolled. Initially, 4 field techniques (anterior, posterior, right lateral, left lateral) will be utilized to treat central tumors using fractionation schemes that are currently considered standard of care. Patients with pelvic malignancies (i.e. rectal cancers, cervical cancers, endometrial cancers) or other malignancies requiring simple four field techniques will be identified for this stage. As well, breast patients requiring a simple tangential opposed pair beam arrangement or 3 - 4 field technique (to include the supraclavicular nodal regions) will be enrolled, with preference for standard hypofractionation schedules, if possible. In stage 3, 10 to 28 participants with malignancies (primarily curable, but incurable malignancies may also be considered) that require more complicated multi-field 3DCRT treatments (not requiring IMRT) for their external beam radiotherapy (i.e. lung, brain, etc.) will be enrolled. This will include the use of field-in-field techniques such as step-and-shoot techniques to allow for modulation of the radiation beam during treatment. In stage 4, 10 to 28 participants with malignancies (primarily curable, but incurable malignancies may also be considered) that require more complicated multi-field IMRT treatments for their external beam radiotherapy (i.e. prostate, head and neck, lung, brain, etc.) will be enrolled.

Official Title
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Northern Alberta Linac-MR Image-Guided Human Clinical Trials - 2

Conditions
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Cancer

Intervention / Treatment
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* Device: MR guided radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 years of age Patients deemed fit to undergo external beam radiation therapy by their attending radiation oncologist Accessible for follow-up Exclusion Criteria: Patients with contraindications for MRI Patients who are unable to lie flat and still for the duration of the expected scan acquisition and treatment Patients who are unable to provide informed consent Patients with clinically significant inferior treatment plans compared to standard CT based external beam plans. For example, plans that generate hot spots of > 110% or other unacceptable treatment plans that would not otherwise arise with standard CT based external beam plans. Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MR guided radiotherapy<br>MR-guided radiotherapy using the Alberta linac-MR P3 system. Contemporary radiotherapy techniques and fractionation schedules will be conducted in the following graduated stages with overlap between stages allowed: Stage 1: Parallel-opposed pair treatments (palliative) Stage 2: 4 field box and breast treatments (curative or palliative) Stage 3: Radical treatments - multi-field 3DCRT (curative) Stage 4: Radical treatments - multi-field IMRT (curative) | Device: MR guided radiotherapy<br>* MR guided radiotherapy using the Alberta linac-MR P3 system<br>* Other names: Alberta linac-MR P3 system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants that complete a course of external beam radiotherapy with the Alberta linac-MR P3 system | The total number of participants completing, without clinically unacceptable interruptions, a course of treatment on the Alberta linac-MR P3 system. The study will track the number of participants that complete treatment without any significant interruptions or delays in their treatment. | Approximately 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute toxicity | Acute toxicity (within 6 months post treatment) graded according to CTCAE version 5.0 will be assessed when all participants have completed a minimum of 1 year follow-up. | 6 months post treatment | 
| Incidence of late toxicity | Late toxicity (greater than 6 months post treatment) graded according to CTCAE version 5.0 will be assessed when all participants have completed a minimum of 1 year follow-up. | between 6 months and 5 years post treatment | 
| Quantify the patient experience on the Linac-MR | Participants will complete a questionnaire at the end of their MR guided radiotherapy. The questionnaire will assess participant comfort and their perception of the treatment experience using a 1 - 5 scale. | 1 year post treatment | 
| Overall treatment time | The total MR guided radiotherapy time will be recorded for each participant, which is comprised of the sum of time the participant is in the treatment room and the total treatment time daily. The overall treatment duration should not exceed the original scheduled treatment duration via conventional radiotherapy by more than five business days, in case of unexpected servicing needs or any other delays. | 1 year post treatment | 
| Overall treatment planning time | The total treatment planning time using the Linac-MR will be recorded for each participant. The overall treatment planning time should be within the currently accepted ready to treat timelines for conventional radiotherapy. | 1 year post treatment | 
| Time to local control | Time from treatment until the recurrence of disease locally. | Up to 5 years after completion of treatment | 
| Disease-free survival | Time from treatment until the recurrence of disease (or death). | Up to 5 years after completion of treatment | 
| Overall survival | Time from treatment until death from any cause. Survival status will be assessed at 12 months following completion of treatment, then annually for up to 5 years. | Up to 5 years after completion of treatment |