CONFIRM: Magnetic Resonance Guided Radiation Therapy

Study Overview
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Brief Summary
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This research is being done to determine the safety and feasibility of using a type of radiation guided by magnetic resonance imaging (MRI) and chemotherapy to treat patients with gastric and breast cancer. The name of the radiation machine involved in this study is the MRIdian Linear Accelerator.

Detailed Description
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This is a master clinical protocol evaluating magnetic resonance (MR) image guided radiation in patients with gastric and breast cancer. In this research study, the investigators are researching if getting an MRI during radiation is a feasible way to delivery radiation. In this research study, a MRI done during treatment will help doctors adapt the radiation to target the most precise spot where the cancer is located. The research study procedures include: Screening for eligibility Study treatment including evaluations Follow up visits Questionnaires This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of investigational radiation treatment and also tries to define the appropriate dose of the investigational radiation treatment to use for further studies. Investigational means that the way the radiation treatment is delivered is being studied. 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. Investigators at other hospitals and academic centers are already using this type of radiation. The U.S. Food and Drug Administration (FDA) has approved this radiation machine and these drugs as treatment options for gastric and breast cancer.

Official Title
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Clinical Onboard Utilization of Image Guided Radiation Therapy With Magnetic Resonance (CONFIRM): A Master Protocol

Conditions
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Gastric Cancer, Invasive Breast Cancer, in Situ Breast Cancer, Mantle Cell Lymphoma, Larynx Cancer, Bladder Cancer

Intervention / Treatment
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* Radiation: Viewray MRIdian® Linac


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have histologically or cytologically confirmed malignancy requiring radiation 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. Any further criteria listed in the specific disease site cohort Exclusion Criteria History of allergic reactions attributed to gadolinium-based IV contrast -- Note: If patient will not receive contrast, this is not applicable and kidney function will not affect eligibility Severe claustrophobia or anxiety Participants who cannot undergo an MRI Any other exclusion criteria listed in the specific disease site cohort

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I - Gastric Cancer<br>The research study procedures include: Screening for eligibility Study treatment including evaluations MR-image guided radiation will be administered per disease site standards. Follow up visits Questionnaires | Radiation: Viewray MRIdian® Linac<br>* MR-image guided radiation will be administered per disease site standards.<br>|
| Experimental: Phase I - Breast Cancer<br>The research study procedures include: Screening for eligibility Study treatment including evaluations MR-image guided radiation will be administered per disease site standards. Follow up visits Questionnaires | Radiation: Viewray MRIdian® Linac<br>* MR-image guided radiation will be administered per disease site standards.<br>|
| Experimental: Phase I - Mantle Cell Lymphoma<br>The research study procedures include: Screening for eligibility Study treatment including evaluations MR-image guided radiation will be administered per disease site standards. Follow up visits Questionnaires | Radiation: Viewray MRIdian® Linac<br>* MR-image guided radiation will be administered per disease site standards.<br>|
| Experimental: Phase I - Larynx<br>The research study procedures include: Screening for eligibility Study treatment including evaluations MR-image guided radiation will be administered per disease site standards. Follow up visits Questionnaires | Radiation: Viewray MRIdian® Linac<br>* MR-image guided radiation will be administered per disease site standards.<br>|
| Experimental: Phase I - Bladder<br>The research study procedures include: Screening for eligibility Study treatment including evaluations MR-image guided radiation will be administered per disease site standards. Follow up visits Questionnaires | Radiation: Viewray MRIdian® Linac<br>* MR-image guided radiation will be administered per disease site standards.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients and delivering MR-image guided radiation-Phase I | Master feasibility study evaluating MR-image guided radiation. Feasibility is defined as Enrolling patients and delivering MR-image guided radiation on the MR Linac | 5 weeks | 
| Tumor Assessment with MR Guidance-Phase I | Master feasibility study evaluating MR-image guided radiation. Feasibility is defined as assessing tumor using MR guidance before, during and after MR-guided treatment patient. | 5 weeks | 
| Patient reported outcomes (PROMs) -Phase II | PROMs are collected at patient visits. PROMs will be evaluated using the Patient-Reported Outcomes Measurement Information System (PROMIS). The PROMIS Global-10 metric collects information on symptoms and quality of life. | 1 year | 
| 1-year tumor control-Phase II | Tumor response 1 year after radiation treatment | 1 year | 
| Rate of Pathologic complete response-Gastric | full pathological review of surgical specimen according to the AJCC Staging Classification, 8th edition. pCR will be defined as the absence of any viable tumor cells within the pathologic specimen. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment Related Adverse Events as Assessed CTCAE version 5.0. | Toxicity of MRgRT with concurrent chemotherapy will be summarized by category and grade according to CTCAE version 5.0. | 90 Days | 
| Number of Participants with Treatment Related Adverse Events as Assessed CTCAE version 5.0. | CTCAE version 5.0. | 1 year | 
| Duration of treatment with goal of >80% of cases treated within 90 minutes | Total time of treatment for each fraction | 7 weeks | 
| Number of treatment fractions that would have resulted in unacceptably high dose (exceeding constraint) to an OAR without MR-image guided radiation. | Importance of MR-guidance | 5 Weeks | 
| Progression Free Survival | Estimated using the Kaplan Meier method with 95% confidence intervals based on the complementary log-log transformation. | irst date of protocol therapy to the earliest date of disease progression per RECIST criteria or death due to any cause up to 12 Months | 
| Overall Survival | The OS rate will be estimated using the Kaplan-Meier method with 95% confidence intervals based on the complementary log-log transformation. | irst date of protocol therapy to the date of death due to any cause. OS time will be censored at the date of last follow-up for patients still alive up to 1 year | 
| Characterizing MRI-based tumor alterations/changes following MR-image guided radiation | Evaluation of tumor response following treatment | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Invasive Breast Cancer, in Situ Breast Cancer, Lymphoma, Larynx, Bladder