Title
UW18110: A Phase I Study of OAR-Based, Dose Escalated SBRT with Real Time Adaptive MRI Guidance for Liver Metastases

Description
Stereotactic Body Radiation Therapy (SBRT) is a noninvasive local therapy with proven efficacy in a number of solid tumor types. However, colorectal cancer (CRC) liver metastases have been shown to be particularly resistant to SBRT, and often are found to have significantly worse rates of control compared with other histologies. Higher SBRT dose was recently shown to improve local control in CRC pulmonary metastases, however, increasing dose delivery with SBRT has been limited based on the risk of toxicity to adjacent structures, and the ability to visualize them during treatment. This is particularly relevant in treating liver tumors, as tumor and small bowel movement can often make tumor targeting and organs-at-risk (OAR) avoidance especially difficult. MRI-guided SBRT for liver tumors is both safe and feasible and offers an as yet unprecedented opportunity to achieve the highest possible safe dose to liver tumors.
The purpose of this trial is to identify a safe maximum tolerated dose level for MRI-guided SBRT treatment of bowel and liver metastases, respectively.
Eligible participants will be on study for up to 12 months.

Objective
Primary Outcome Measures:

Number of Participants with Acute Dose Limiting Toxicity (DLT) [ Time Frame: Up to 4 weeks ]


Dose limiting toxicity (DLT) will be defined as grade 3 or greater* non-hematologic toxicity attributable to radiation therapy, and occurring within 4 weeks after the completion of SBRT. *With the exception of liver function tests, which are allowed up to and including grade 3

Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]


Progression-free survival (PFS) will be defined as the difference (in months) between the date of study enrollment and the date of disease progression or death due to any cause


Overall Survival (OS) [ Time Frame: Up to 5 years ]


Overall survival (OS) will be defined as the difference (in months) between the date of study enrollment to the date death due to any cause.


Local Control Rates [ Time Frame: up to 1 year ]


Point estimates along with the exact 95% confidence interval will be computed for the local control rates

Treatment Experimental: MRI-Guided SBRT Dose Escalation -

Treatment on MRI Linac with SBRT in 5 fractions with adaptive planning, maximum dose 80 Gy

Dose Escalation Bowel Pathway, V34 < 0.5cc Dose Escalation Liver Pathway, 700 cc < 16 Gy

Subsequent Phase 1B: CRC only for Safety and Local Control, dosage informed by Phase 1A

Participants will receive 5 fractions of radiation, which will be delivered 2-3 times per week. SBRT should be complete in a 1.5 to 2 week time frame. There should be a minimum of 12 hours between treatments. Each fraction will be escalated or de-escalated to meet the overall constraints in phase IA or both previously identified constraints in phase IB

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Breast; Colon and Rectum; Lung

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital