Stereotactic Magnetic Resonance Guided Radiation Therapy

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

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

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer; Prostate Cancer; Mesothelioma; Liver Metastases; Pancreas Cancer; Renal Cancer; Brain Metastases; Spine Metastases; Borderline Resectable Pancreatic Carcinoma; Adrenal Metastases; Oligoprogressive Nodal Metastases; Metachronous Nodal Metastases; Synchronous Nodal Metastases
• Intervention / Treatment: Radiation: MR-guided Linac

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 397
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jonathan Leeman, MD; Phone Number: 617-732-6452; Email: JONATHANE_LEEMAN@DFCI.HARVARD.EDU

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Jonathan Leeman, MD
      • Principal Investigator: Jonathan Leeman, MD
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham & Women's Hospital
      • Contact: Jonathan Leeman, MD
      • Principal Investigator: Jonathan Leeman, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

19

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Jonathan Leeman, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Leeman JE, Shin KY, Droznin A, Catalano P, Cagney DN, Singer L, Oniyangi RD, Zhai K, Benham G, Chirmade S, Campbell J, Boyle S, Saranteas A, Williams CL, Huynh E, Han Z, Sudhyadhom A, Hu YH, Ferguson D, Singhrao K, Hsu SH, Bredfeldt J, Martin NE, Mancias JD, Mamon HJ, Van Dams R, Venkatachalam V, Tanguturi SK, Huynh MA, Fitzgerald KJ, Elhalawani H, Bitterman DS, Schoenfeld JD, Nguyen P, Haas-Kogan DA, Mak R. Stereotactic MRI Guided Adaptive Radiotherapy: a pooled analysis of a master prospective trial. J Natl Cancer Inst. 2025 Aug 6:djaf208. doi: 10.1093/jnci/djaf208. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2019
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 3, 2019

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: November 11, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Lung Cancer; Prostate Cancer; Renal Cancer; Pancreas Cancer; Magnetic Resonance Imaging (MRI); Spine; Liver Metastases; Synchronous; MRIdian Linear Accelerator; Adrenal Metastases; Oligoprogressive; Metachronous; Prostate Boost; Pelvic Re Irradiation
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Adenoma; Neoplasms, Mesothelial; Urologic Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Prostatic Neoplasms; Lung Neoplasms; Mesothelioma; Pancreatic Neoplasms; Brain Neoplasms; Kidney Neoplasms
• Other Study ID Numbers: 19-353

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: Dr. Jonathan Leeman (jonathane_leeman@dfci.harvard.edu). The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: BWH - Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No