Stereotactic Magnetic Resonance Guided Radiation Therapy

Study Overview
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Brief Summary
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This is a master prospective Phase I-II trial evaluating feasibility and efficacy of stereotactic magnetic resonance (MR) guided adaptive radiation therapy (SMART) in patients with cancer. The phase 1 study will evaluate the feasibility and safety of delivering SMART in patients with cancer. Phase 2 will evaluate efficacy of SMART with specific reference to tumor control and improvement in patient reported outcome measures

Detailed Description
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This research study is a feasibility study, which means it is the first-time investigators at this institution are examining this type of MR-guided radiation to treat cancer. The U.S. Food and Drug Administration (FDA) has approved this device as a treatment option for cancer. In this research study, the investigators are hoping to determine if adjusting radiation treatments based on daily MRI has a feasible way to deliver radiation for participants with pancreatic, lung or renal cancer.

Official Title
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A Master Protocol of Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy (SMART)

Conditions
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Pancreas Cancer, Lung Cancer, Renal Cancer, Adrenal Metastases, Prostate Cancer, Liver Metastases, Oligoprogressive Nodal Metastases, Metachronous Nodal Metastases, Synchronous Nodal Metastases, Mesothelioma, Spine Metastases, Brain Metastases, Borderline Resectable Pancreatic Carcinoma

Intervention / Treatment
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* Radiation: MR-guided Linac


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a confirmed malignancy requiring stereotactic body radiation therapy. See specific disease site cohorts for more details. Tumor size ≤ 7cm Age 18 years of older. ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A) Ability to understand and the willingness to sign a written informed consent document. Specific eligibility requirements for each disease site with be covered in each specific cohort. Exclusion Criteria: Specific exclusion requirements for each disease site with be covered in each specific cohort History of allergic reactions attributed to gadolinium-based IV contrast. -- Note: If a patient will not receive contrast, this is not applicable Pregnant women are excluded from this study. Severe claustrophobia or anxiety Participants who cannot undergo an MRI

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants will be assigned to one treatment arm only depending on their cancer type, and will be taken off study once treatment and follow up are complete.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Pancreatic<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Renal<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Central Lung<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Adrenal Metastases<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Liver Metastases<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Metachronous Oligometastatic Nodes<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Oligoprogressive Oligometastatic Nodes/Soft Tissue<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Synchronous Oligometastatic Nodes/Soft Tissue<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Prostate<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Borderline Resectable Pancreas<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Brain Metastases<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Mesothelioma<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Prostate Boost<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Pelvic Re-Irradiation<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Spine<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Single-Fraction Kidney Tumors<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--1/3 Fraction for Oligometastatases in the Abdomen/Pelvis<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Post-Operative Radiation Therapy in Lung Cancer<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|
| Experimental: PHASE 1: SBRT MR IMAGE GUIDANCE/ADAPTATION--Mediastinal and Hilar Lymph Nodes<br>SMART will be administered per each individual disease site standards | Radiation: MR-guided Linac<br>* Radiation will be delivered on an MR-guided Linear Accelerator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery Success Rate for SMART across multiple tumors-Phase I | Enrolling patients and delivering SMART on the MR Linac | 1 year | 
| Tumor visualization-Phase I | Assessing tumor using MR guidance before, during and after MR-guided treatment patient | 1 Year | 
| Plan creation-Phase I | Generating adaptive plans | 1 Year | 
| Rate of Improvement in Tumor Control-Phase II | Statistical power will be defined in each cohort individually and will be specific to each disease site tested. | 1 Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients with Acute Toxicity-Phase I | Any related ≥ Grade 3 AE which is possibly, probably or definitely related to SMART | 90 Days | 
| Duration of treatment-Phase 1 | Duration of treatment with goal of >80% of cases treated within 90 minutes | 90 Days | 
| Number of treatment fractions-Phase1 | Number of treatment fractions that would have resulted in unacceptably high dose (exceeding constraint) to an OAR without SMART | 90 Days | 
| Number of Participants with long term toxicity-Phase II | assessing long-term (12 month) toxicity in patients receiving SMART | 365 Days | 
| Disease Specific Survival Rate-Phase II | Kaplan-Meier curve estimates | 365 Days | 
| Overall Survival Rate-Phase II | Kaplan-Meier curve estimates | 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic Resonance Imaging (MRI), MRIdian Linear Accelerator, Pancreas Cancer, Lung Cancer, Renal Cancer, Adrenal Metastases, Prostate Cancer, Liver Metastases, Oligoprogressive, Metachronous, Synchronous, Spine, Prostate Boost, Pelvic Re Irradiation