Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction

Study Overview
=================
Brief Summary
-----------------
This is a multi-site single arm feasibility study of single-fraction Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) for primary or metastatic carcinoma involving the lung, liver, adrenal gland, abdominal/pelvic lymph node, pancreas, and/or kidney. Stereotactic ablative body radiation therapy (SABR) is a highly-focused radiation treatment that gives an intense dose of radiation concentrated on a tumor, while limiting the dose to the surrounding organs.

Official Title
-----------------
A Feasibility Study of Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) in One Fraction for Inoperable Primary or Metastatic Carcinoma (SMART ONE)

Conditions
-----------------
Metastatic Carcinoma

Intervention / Treatment
-----------------
* Radiation: Stereotactic ablative body radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Subject must be ≥18 years of age at the time of study enrollment Subject must have Biopsy-confirmed primary or metastatic carcinoma with involvement of the lung, liver, adrenal gland, pancreas, kidney, and/or abdominal/pelvic lymph node that would receive SABR Any lesion that would receive SABR under this study protocol is no larger than 5 cm in greatest dimension 1-10 total lesions that would receive SABR If multiple lesions are treated, they must be at least 3 cm apart Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Life expectancy at least 6 months Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Abstinence is acceptable if it's the patient preferred method. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Patients receiving hormonal therapy or immunotherapy such as immune checkpoint inhibitor that had begun at least 4 weeks prior to SABR will be allowed. Exclusion criteria Subject has contraindication to having an MRI scan Subject has central or ultra-central lung tumor that would receive SABR on this study, defined as a lesion located within 2 cm of the trachea and proximal bronchial tree Subject has received cytotoxic chemotherapy or investigational agent within 2 weeks of SBRT Subject has uncontrolled brain metastases, spinal cord compression, or leptomeningeal carcinomatosis Subject has any unresolved toxicity (Common Terminology Criteria for Adverse Events version 5.0 > grade 2) from previous anti-cancer therapy Subject has any condition in the opinion of the investigator that would interfere with evaluation of study treatment or interpretation of patient safety or study results Subject has received prior radiation therapy that directly overlaps any radiation therapy given in this study Subject has received radiation therapy that could lead to an unacceptably high risk of clinically significant normal tissue injury due to high cumulative normal tissue dose as determined by the investigator Female subject who are pregnant or breastfeeding Subject who has received vascular endothelial growth factor (VEGF) inhibitor such as bevacizumab within 4 weeks prior to study therapy or planned to receive it within 4 weeks after study therapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single-fraction SABR<br>Patients will receive SABR in a single-fraction regiment treatment with one single dose of radiation therapy per lesion. Patients may be treated for up to a total of ten lesions. Each lesion will be treated in one fraction. | Radiation: Stereotactic ablative body radiation therapy<br>* Single-fraction of stereotactic ablative body radiation (SABR) therapy will be delivered with an integrated magnetic resonance imaging (MRI)-guided radiotherapy delivery system (ViewRay MRIdian Linac). The prescription dose is dependent on the anatomic location of the lesion and based on previously published safety data.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of SABR successfully delivered in one fraction | Number of SABRs that meet the following criteria: Successful completed for each lesion within 3 days of intended treatment Successful completion of treatment to each lesion within 90 minutes from the patient entering the treatment room until treatment completion Image guidance verification of treatment delivery within 5 mm of the planned delivery | through study completion, an average of 1 year | 
| Number of patients demonstrating tolerability | Number of patients that meet the following criteria: No greater than 4 of 30 patients experience grade 3 or higher acute toxicity within 90 days of completing SABR No grade 5 toxicity is attributed to SABR | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in one-year local control | Change in one-year local control will be assessed according to RECIST 1.1 criteria and will be estimated using the Kaplan-Meier method along with the corresponding 95% confidence interval from the time of study treatment. | baseline, up to 12 months after treatment | 
| Number of participants with one-year overall survival | Number of participants with one-year overall survival will be estimated using the Kaplan-Meier method along with the corresponding 95% confidence interval from the time of study treatment. | 12 months after treatment | 
| Proportion of participants with a change in acute and late toxicity results | Proportion of participants with a change in acute and late toxicity results who experience acute grade 3 or higher toxicity attributable to SABR will be determined along with the corresponding 95% confidence interval. For patients receiving SABR to multiple lesions, acute toxicity will be determined from the date of the initiation of SABR. | baseline, during treatment, up to 12 months after treatment | 
| Change in participant reported quality of life questionnaire | Patient-reported quality of life will be determined using the FACT-G survey instrument. Fact-G is a 27-item questionnaire that covers four HR-QOL sub-domains: physical, social, emotional, and function well being. Each question will be scored from a scale from 0 (not at all) to 4 (very much) using a manual scoring template in which some items are reverse. | baseline, up to 12 months after treatment |