Liver MetastasesNCT04020276
OAR-Based, Dose Escalated SBRT With Real Time Adaptive MRI Guidance for Liver Metastases
A study testing SBRT in people with Liver Metastases and Stereotactic Body Radiation Therapy, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The purpose of this trial is to identify a safe maximum tolerated dose level for MRI-guided Stereotactic Body Radiation Therapy (SBRT) treatment of bowel and liver metastases, respectively. Eligible participants will be on study for up to 12 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastases, Stereotactic Body Radiation Therapy, MRI-guided Treatment
- What is being tested?
- SBRT
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Nov 2019to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a diagnosis of histologically confirmed or clinically suspected metastatic cancer to the liver.
- Participant must be a candidate for SBRT to at least one intrahepatic lesion but no more than 6 intrahepatic lesions.
- Participant must be a candidate for treatment on the ViewRay treatment unit. Must be screened to rule out implants and devices that are not MRI compatible.
- Be willing and able to provide written informed consent.
- Participants may be therapy-naïve or have had prior systemic therapy up to two weeks prior to study entry.
- No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS involvement must meet all of the following to be eligible:
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- At least 28 days from prior definitive treatment of their CNS disease by surgical resection, SBRT or Whole Brain Radiation Therapy (WBRT) at the time of registration
- AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing antiepileptic medications for brain metastases for >14 days prior to registration.
- Demonstrate adequate organ function as defined in the following table; all screening labs should be performed within 28 days of SBRT treatment initiation.
- Platelet count greater than or equal to 50000 /µL
- Absolute Neutrophil Count (ANC) greater than or equal to 1000 /µL
- Hemoglobin (Hgb) greater than or equal to 8 g/dL or greater than or equal to 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
- Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) Creatinine/Calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min for subject with creatinine levels greater than 1.5 X institutional upper limit of normal (ULN)
- Bilirubin greater than or equal to 1. 5 × ULN OR direct bilirubin greater than or equal to ULN for participants with total bilirubin levels greater than 1.5 ULN
- Aspartate aminotransferase (AST) and ALT (SGPT) greater than or equal to 5 × ULN
- International Normalized Ratio (INR) or Prothrombin Time (PT) greater than or equal to 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) greater than or equal to 1.5 X ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- For participants enrolled on the liver dose escalation arm, screening labs must be consistent with Child Pugh class A unless therapeutic anticoagulation places them in Child Pugh B. In that case, trial entry or exclusion will be at the discretion of the treating physician.
- Have a performance status of 2 or less on the Eastern Cooperative Oncology Group (ECOG) performance scale.
- Life expectancy of > 12 weeks.
- Women of childbearing potential (WOCP) should have a negative urine or serum pregnancy test prior to initiation of radiation therapy. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- WOCP must not be pregnant or breast-feeding.
- WOCP must be willing to use an effective method of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence for the duration of the radiotherapy and 60 days thereafter.
- NOTE: A person of childbearing potential is anyone (regardless of sexual orientation, gender identity, having undergone a tubal ligation, or remaining celibate by choice) who was born with a uterus and at least one ovary and meets both of the following criteria:
- Is post-menarcheal (i.e., has had at least one prior menses)
- Has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Participant is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the initiation of SBRT.
- History of a second invasive cancer in the last 3 years (except for appropriately treated low-risk prostate cancer, treated non-melanoma skin cancer, appropriately treated ductal carcinoma in situ or early stage invasive carcinoma of breast appropriately treated in situ/early stage cervical/endometrial cancer.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with follow up scans or visits.
- Has a primary tumor histology of germ cell tumor, leukemia, or lymphoma.
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- Has a primary liver cancer such as cholangiocarcinoma or hepatocellular carcinoma.
- Has had prior radiation therapy that significantly overlaps with the liver.
- Has a diagnosis of Crohn's disease, ulcerative colitis, or scleroderma.
- Participants with Gilbert's disease or other primary disorders of bilirubin metabolism will not be allowed on the trial.
- For participants in the liver dose escalation arm only, has pre-existing liver disease such that patients are classified as Child Pugh B or worse. If the participant is anti-coagulated such that their INR places them in the CP-B classification, exclusion or inclusion will be at the discretion of the treating physician.
- Pregnancy or women of childbearing potential and men who are sexually active and refuse to use medically acceptable forms of contraception.
- Participants with implanted hardware that would preclude MRIs.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Wisconsin
Madison, Wisconsin, 53792
Cancer Connect, 800-622-8922, clinicaltrials@cancer.wisc.edu
About this study
Official title: A Phase I Study of OAR-Based, Dose Escalated SBRT With Real Time Adaptive MRI Guidance for Liver Metastases
The purpose of this trial is to identify a safe maximum tolerated dose level for MRI-guided Stereotactic Body Radiation Therapy (SBRT) treatment of bowel and liver metastases, respectively.
Eligible participants will be on study for up to 12 months.
Read the detailed description
Stereotactic Body Radiation Therapy (SBRT) is a noninvasive local therapy with proven efficacy in a number of solid tumor types. The technique itself involves the precise administration of high biological equivalent dose radiation in order to maximize local control of discrete lesions.
SBRT has been shown to be an effective therapy for both primary and metastatic liver tumors of multiple histologies. In metastatic liver disease from all primary tumor sites, patients treated with modern SBRT techniques generally enjoy very high levels of 1 and 2 year local control. However, 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. Recent studies indicate this might be due to the inherent radioresistance of the CRC histology.
Despite this, there appears to be a relationship between increasing dose and improvement of local control, both within CRC and other tumor histologies. Higher SBRT dose was recently shown to improve local control in CRC pulmonary metastases, further corroborating the hypothesis of CRC as a radioresistant tumor. 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.
Primary Objectives:
- To determine the safety and tolerability of using increasing bowel dose constraints for MRI-guided SBRT treatment of metastatic liver deposits from all primary histologies except as outlined in the exclusion criteria.
- To determine the safety and tolerability of using increasing volume-based liver constraints for MRI-guided SBRT treatment for metastatic liver deposits from all primary histologies except as outlined in the exclusion criteria.
- To define maximally tolerated dose constraints for both liver and bowel based on DLT using real-time, adaptive, MRI-based treatment planning.
Secondary Objectives:
- To determine local recurrence rates at 1, and 2 years using MRI-guided SBRT with dose planning from escalation of OAR constraints.
- To evaluate progression-free survival (PFS) and overall survival (OS) in this patient cohort.
- To assess quality of life and patient reported outcomes at 2 months following MRI-guided SBRT.
- Being tested
- SBRT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| MRI-Guided SBRT Dose Escalation | Experimental | 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 Receives: Radiation: SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Acute Dose Limiting Toxicity (DLT)
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
Measured: Up to 4 weeks
Secondary outcomes (4)
Progression Free Survival (PFS)
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
Measured: Up to 5 years
Overall Survival (OS)
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.
Measured: Up to 5 years
Local Control Rates
Point estimates along with the exact 95% confidence interval will be computed for the local control rates
Measured: up to 2 years
Change in Quality of Life (QoL)
QoL will be assessed on a 5 item questionnaire using a 4-point Likert scale, where 4 = Not at all and 1 = Constant. Scores range from 5-20 where higher scores indicate better quality of life.
Measured: Baseline, 2 months (1 month post treatment follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start4 Nov 2019
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 4+4 dose-escalation design - patients will be treated to a maximum tolerated dose using MRI-guided SBRT with real time adaptation.
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Bassetti, MD, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04020276
- Sponsor's protocol ID
- 2019-0373
- Other IDs
- NCI-2019-04726, SMPH/HUMAN ONCOLOGY/HUMAN ONCO, A533300, UW18110, Protocol Version 10/28/2025
- Status last verified
- Jun 2026
- First submitted
- 11 Jul 2019
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of OAR-Based, Dose Escalated SBRT With Real Time Adaptive MRI Guidance for Liver Metastases
- ClinicalTrials.gov ID
- NCT04020276
- Acronym / sponsor ID
- 2019-0373
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 16 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to identify a safe maximum tolerated dose level for MRI-guided Stereotactic Body Radiation Therapy (SBRT) treatment of bowel and liver metastases, respectively.
Eligible participants will be on study for up to 12 months.
Detailed description
Stereotactic Body Radiation Therapy (SBRT) is a noninvasive local therapy with proven efficacy in a number of solid tumor types. The technique itself involves the precise administration of high biological equivalent dose radiation in order to maximize local control of discrete lesions.
SBRT has been shown to be an effective therapy for both primary and metastatic liver tumors of multiple histologies. In metastatic liver disease from all primary tumor sites, patients treated with modern SBRT techniques generally enjoy very high levels of 1 and 2 year local control. However, 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. Recent studies indicate this might be due to the inherent radioresistance of the CRC histology.
Despite this, there appears to be a relationship between increasing dose and improvement of local control, both within CRC and other tumor histologies. Higher SBRT dose was recently shown to improve local control in CRC pulmonary metastases, further corroborating the hypothesis of CRC as a radioresistant tumor. 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.
Primary Objectives:
- To determine the safety and tolerability of using increasing bowel dose constraints for MRI-guided SBRT treatment of metastatic liver deposits from all primary histologies except as outlined in the exclusion criteria.
- To determine the safety and tolerability of using increasing volume-based liver constraints for MRI-guided SBRT treatment for metastatic liver deposits from all primary histologies except as outlined in the exclusion criteria.
- To define maximally tolerated dose constraints for both liver and bowel based on DLT using real-time, adaptive, MRI-based treatment planning.
Secondary Objectives:
- To determine local recurrence rates at 1, and 2 years using MRI-guided SBRT with dose planning from escalation of OAR constraints.
- To evaluate progression-free survival (PFS) and overall survival (OS) in this patient cohort.
- To assess quality of life and patient reported outcomes at 2 months following MRI-guided SBRT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 4+4 dose-escalation design - patients will be treated to a maximum tolerated dose using MRI-guided SBRT with real time adaptation.
| Arm | Type | Receives |
|---|---|---|
| MRI-Guided SBRT Dose Escalation | Experimental | Radiation: SBRTTreatment 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Have a diagnosis of histologically confirmed or clinically suspected metastatic cancer to the liver.
- Participant must be a candidate for SBRT to at least one intrahepatic lesion but no more than 6 intrahepatic lesions.
- Participant must be a candidate for treatment on the ViewRay treatment unit. Must be screened to rule out implants and devices that are not MRI compatible.
- Be willing and able to provide written informed consent.
- Participants may be therapy-naïve or have had prior systemic therapy up to two weeks prior to study entry.
Key exclusion criteria (13 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the initiation of SBRT.
- History of a second invasive cancer in the last 3 years (except for appropriately treated low-risk prostate cancer, treated non-melanoma skin cancer, appropriately treated ductal carcinoma in situ or early stage invasive carcinoma of breast appropriately treated in situ/early stage cervical/endometrial cancer.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with follow up scans or visits.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRTParticipants 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. | Radiation | MRI-Guided SBRT Dose Escalation |
Primary outcome
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
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: Up to 5 years
Overall Survival (OS)
Time frame: Up to 5 years
Local Control Rates
Time frame: up to 2 years
Change in Quality of Life (QoL)
Time frame: Baseline, 2 months (1 month post treatment follow-up)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- University of Wisconsin Carbone Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Bassetti, MD, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SBRT in people with Liver Metastases and Stereotactic Body Radiation Therapy, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cancer Connect (800-622-8922, clinicaltrials@cancer.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Acute Dose Limiting Toxicity (DLT) (time frame: Up to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.