Liver CancervGRID SBRTNCT05727787
vGRID SBRT: A Phase I Clinical Trial in Unresectable or Metastatic HCC
A study testing Stereotactic Body Radiation Treatment in people with Liver Cancer, run by University of Kansas Medical Center at 1 site in United States.
Trial summary
This trial will provide the maximum tolerated dose for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cancer
- What is being tested?
- Stereotactic Body Radiation Treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Feb 2023to 31 Aug 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
- Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent .
- Males and females age ≥ 18 years.
- ECOG Performance Status 0 - 1
- Histologically confirmed hepatocellular carcinoma (HCC) or mixed HCC and cholangiocarcinoma either locally advanced or metastatic.
- Not a candidate for surgical resection, or transplant
- Child Pugh A - B7 liver function scale classification 14 days prior to entry.
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- Unresectable, locally-advanced or metastatic hepatocellular carcinoma. Meets normal liver and adjacent organ radiation dose constraints, which usually corresponds to tumor sizes 4 - 12 cm in diameter. Tumors that are larger than 12cm are permitted provided radiation dose constraints to adjacent normal tissue are met per radiation dose constraint table
- Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to initiating study intervention. Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use an acceptable form of contraception for the duration of study participation, and for at least 12 months following completion of therapy. Men of child-bearing potential must agree not to donate sperm while on this study and for at least 12 months after their last study treatment.
- Adequate organ function, defined as follows: Result Date
- Hemoglobin ≥8 g/dL (The use of transfusion is acceptable)
- Absolute Neutrophil Count > 1.0 K/UL
- Platelets > 50 K/UL
- AST and ALT < 6 times upper limit of normal (ULN)
- Albumin >2.9g/dl
- Prothrombin/INR < 1.7
- Creatinine < 1.5x ULN or creatinine clearance > 60 mL/min
- Total Bilirubin < 3.0
- Esophageal varices, if present, must be < Grade 2 and can not have had bleeding in the last 6 months. If clinically indicated, a standard care Esophageal Gastric Duodenoscopy (EGD) is recommended to rule out uncontrolled esophageal varices. NOTE: EGD is not required for enrollment.
- Documented virology status of hepatitis, as confirmed by HBV / HCV serology test. Patients with known hepatitis are allowed on this study provided they meet all other eligibility criteria. Concomittant therapy for hepatitis is permitted at the principal investigator's discretion.
- No known history or suspected human immunodeficiency virus (HIV). Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ (350) cells/microliter, and no known detectable viral load, at the time of study entry. Note also that HIV testing is not required for eligibility for this protocol.
Who cannot join
- Hepatocelluar carcinoma (HCC) or other mixed subtype (fibrolamellar HCC, or sarcomatoid HCC) amenable to curative surgery or transplant
- Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements.
- Is pregnant or breastfeeding.
- Prior Abdominal radiation, including prior arterial Yttrium therapy.
- History of autoimmune disease.
- Current use of immunosuppressive drugs, such as corticosteroids, or TNF-alpha blockers.
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- Concurrent active secondary malignancy, excluding indolent cancers such as treated cutaneous malignancies or treated chronic lymphocytic leukemia, or prior cancers now in remission for 3 years or longer.
- Direct tumor extension into the stomach or duodenum. Small bowel or large bowel or untreated esophageal varices greater than Grade 3 are not allowed.
- Measureable common or main branch biliary duct involvement with HCC.
- Severe active co-morbidities
- All participants: Participants should not donate blood or blood components while participating in this study and through 180 days after the last study dose.
- Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Patients with clinically relevant ongoing complications from prior surgery are not eligible.
- History of organ transplantation.
- Uncontrolled hypertension despite optimal antihypertensive treatment in the opinion of the principal investigator.
- Uncontrollable ascites or pleural effusion.
- Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 8 weeks before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
- Active autoimmune disease (active defined as having autoimmune disease related symptoms and detectable autoantibodies) that has required systemic treatment in the past 2 years.
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs. Except Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent, Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- Clinically significant gross hematuria, hematemesis, or hemoptysis of >0.5 tsp (2.5ml) of red blood, or other history of grade 3 significant bleeding within 8 weeks.
- 22. Cholangiocarcinoma (intra/extra-hepatic).
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 Kansas Medical Center
Kansas City, Kansas, 66160
Amanda Schroeder, MPH, 913-588-3600, aschroeder3@kumc.edu
Maggie Messplay, BS, 913-588-3610, smessplay@kumc.edu
About this study
This trial will provide the maximum tolerated dose for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is likely that vGRID therapy in this trial will be well tolerated and allow dose escalation beyond currently common doses for liver tumors.
Read the detailed description
While 30 Gy in a single-dose SBRT has been demonstrated to be safe for liver tumors, higher radiation dose is likely required to control larger tumors. Radiation dose escalation beyond 30 Gy to the entire tumor will be significantly limited by potential toxicity to nearby tissues and organs. vGRID therapy, which treats part of the tumor to a high dose while the rest of the tumor to a lower dose, may allow safe dose escalation beyond 30 Gy. As described above, our treatment planning simulation has demonstrated an ability to safely dose escalate using the vGRID technique while keeping radiation doses to surrounding tissues and organs to lower than well-accepted dose limits.
The overall goal of this study is to assess the MTD of SBRT to live tumors using the vGRID radiation technique. We have specifically chosen dose level 1 to be 27 Gy (below the 30 Gy SBRT dose used in the trial by Goodman et al which was demonstrated to be safe). Further, this dose of 27 Gy x 1 will have a point dose biological equivalent dose (BED) of 100 (using alpha/beta ratio of 10), similar to the BED of 100 used in the cooperative group trial RTOG 1112 for HCC. While unlikely, if DLT's are experienced in our lowest dose cohort, we will de-escalate radiation dose to 40 Gy in 5 fractions (BED 72) which was previously shown to be safe in Child's Pugh Class B patients, with a 2 year LC of 90% (Andolino IJROBP 2011).
The dose levels for this phase I trial are: 1) 27 Gy, 2) 32 Gy, 3) 37 Gy, 4) 42 Gy, 5) 47 Gy. Our third highest dose of 37 Gy x1 has a BED of 173.9 (alpha/beta ratio of 10), which is similar to Rusthoven's 60 Gy in 3 fractions for liver metastases (Rusthoven JCO 2009).
Our highest dose cohort is 47 Gy x 1, which has a BED of 267.9 to the tumor, will represent significant dose escalation compared to current treatment (2.7x the biological dose to tumor), and if found to be safe, will be used for the future Phase II trial.
This trial will provide the MTD for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is likely that vGRID therapy in this trial will be well tolerated and allow dose escalation beyond currently common doses for liver tumors.
The safety of this trial is maximized by treatment planning following strict dose limits to nearby tissues and organs. Even though part of the tumor will receive dose escalated vGRID radiation, treatment plans must meet strict criteria regarding dose limits to nearby tissues and organs that are known to be safe to patients.
Upon completion of vGRID radiation, patients will than begin treatment standard of care treatment option Atezolizumab. The rationale for following vGRID radiation followed Atezolizumab is to potentiate the immune microenvironment and enhance synergy of anti-tumor effect.
Atezolizumab is often given with bevacizumab per the landmark study IMbrave150 in unresectable HCC patients (Finn RS NEJM 2020). However, given the added risk of GI toxicity from bevacizumab with radiation, we have stipulated in this trial to hold bevacizumab with cycle 1 of atezolizumab, which is to begin 12 - 16 days after completion of radiation.
- Conditions
- Liver Cancer
- Being tested
- Stereotactic Body Radiation Treatment
- Keywords
- Liver Cancer, SBRT, Radiation Treatment
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body Radiation TreatmentRadiation
Single fraction SBRT 27 Gy
| Study group | Role | What they receive |
|---|---|---|
| Single fraction SBRT 27 Gy | Experimental | vGRID SBRT 3+3 dose escalation, single fraction, one day cycle length Receives: Radiation: Stereotactic Body Radiation Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of Single Fraction GRID SBRT
Safely identify MTD of Single Fraction GRID SBRT and CTCAE v5.0 related toxicity:
Irreversible grade 3 hepatotoxicity, grade 4 or 5 hepatotoxicity, grade 4 or 5 gastrointestinal toxicity.
Measured: First day of post-GRID SBRT through 3 month post-radiation
Secondary outcomes (5)
Local control utilizing RECIST v1.1 for HCC.
Local control (irradiated tumor) utilizing modified RECIST criteria for HCC.
Measured: End of treatment through 3 month post-radiation
Regional failure utilizing RECIST v1.1 for HCC.
Regional failure (intrahepatic non-irradiated progression) utilizing modified RECIST criteria for HCC.
Measured: End of treatment through 3 month post-radiation
Progression free survival (PFS)
Progression free survival (PFS), defined as the time from dose level assignment to the first occurrence of disease progression or death from any cause up to 3 months after the end of immunotherapy treatment (disease progression is determined by the investigator according to RECIST v1.1)
Measured: Enrollment through 3-months after end of immunotherapy treatment
Time to Progression (TTP)
Time to Progression (TTP), defined as the time from dose level assignment to the first occurrence of disease progression (disease progression is determined by the investigator according to RECIST v1.1)
Measured: Enrollment through 3-months after end of immunotherapy treatment
Molecular correlatives: TCR repertoire analysis.
T cell receptor Beta Chain sequencing to evaluate TCR repertoire expansion
Measured: Pre-vGRID vs Day 7-12 after vGRID (day 0) and 4-8 weeks after vGRID
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2023
- Study start23 Feb 2023
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Varian Medical Systems
- Responsible party
- Principal investigator, David Akhavan, University of Kansas Medical Center
- Investigators
- David Akhavan, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05727787
- Sponsor's protocol ID
- IIT-2021-GRID-SBRT-HCC
- Acronym
- vGRID SBRT
- Status last verified
- Apr 2025
- First submitted
- 24 Jan 2023
- Last updated
- 24 Dec 2025
- 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 24 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- vGRID SBRT: A Phase I Clinical Trial in Unresectable or Metastatic HCC
- ClinicalTrials.gov ID
- NCT05727787
- Acronym / sponsor ID
- vGRID SBRT / IIT-2021-GRID-SBRT-HCC
- Conditions
- Liver Cancer
- Keywords
- Liver Cancer, SBRT, Radiation Treatment
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Collaborators
- Varian Medical Systems
- Study start
- 23 Feb 2023 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 14 Feb 2023 (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.
This trial will provide the maximum tolerated dose for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is likely that vGRID therapy in this trial will be well tolerated and allow dose escalation beyond currently common doses for liver tumors.
Detailed description
While 30 Gy in a single-dose SBRT has been demonstrated to be safe for liver tumors, higher radiation dose is likely required to control larger tumors. Radiation dose escalation beyond 30 Gy to the entire tumor will be significantly limited by potential toxicity to nearby tissues and organs. vGRID therapy, which treats part of the tumor to a high dose while the rest of the tumor to a lower dose, may allow safe dose escalation beyond 30 Gy. As described above, our treatment planning simulation has demonstrated an ability to safely dose escalate using the vGRID technique while keeping radiation doses to surrounding tissues and organs to lower than well-accepted dose limits.
The overall goal of this study is to assess the MTD of SBRT to live tumors using the vGRID radiation technique. We have specifically chosen dose level 1 to be 27 Gy (below the 30 Gy SBRT dose used in the trial by Goodman et al which was demonstrated to be safe). Further, this dose of 27 Gy x 1 will have a point dose biological equivalent dose (BED) of 100 (using alpha/beta ratio of 10), similar to the BED of 100 used in the cooperative group trial RTOG 1112 for HCC. While unlikely, if DLT's are experienced in our lowest dose cohort, we will de-escalate radiation dose to 40 Gy in 5 fractions (BED 72) which was previously shown to be safe in Child's Pugh Class B patients, with a 2 year LC of 90% (Andolino IJROBP 2011).
The dose levels for this phase I trial are: 1) 27 Gy, 2) 32 Gy, 3) 37 Gy, 4) 42 Gy, 5) 47 Gy. Our third highest dose of 37 Gy x1 has a BED of 173.9 (alpha/beta ratio of 10), which is similar to Rusthoven's 60 Gy in 3 fractions for liver metastases (Rusthoven JCO 2009).
Our highest dose cohort is 47 Gy x 1, which has a BED of 267.9 to the tumor, will represent significant dose escalation compared to current treatment (2.7x the biological dose to tumor), and if found to be safe, will be used for the future Phase II trial.
This trial will provide the MTD for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is likely that vGRID therapy in this trial will be well tolerated and allow dose escalation beyond currently common doses for liver tumors.
The safety of this trial is maximized by treatment planning following strict dose limits to nearby tissues and organs. Even though part of the tumor will receive dose escalated vGRID radiation, treatment plans must meet strict criteria regarding dose limits to nearby tissues and organs that are known to be safe to patients.
Upon completion of vGRID radiation, patients will than begin treatment standard of care treatment option Atezolizumab. The rationale for following vGRID radiation followed Atezolizumab is to potentiate the immune microenvironment and enhance synergy of anti-tumor effect.
Atezolizumab is often given with bevacizumab per the landmark study IMbrave150 in unresectable HCC patients (Finn RS NEJM 2020). However, given the added risk of GI toxicity from bevacizumab with radiation, we have stipulated in this trial to hold bevacizumab with cycle 1 of atezolizumab, which is to begin 12 - 16 days after completion of radiation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single fraction SBRT 27 Gy | Experimental | Radiation: Stereotactic Body Radiation TreatmentvGRID SBRT 3+3 dose escalation, single fraction, one day cycle length |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent .
- Males and females age ≥ 18 years.
- ECOG Performance Status 0 - 1
- Histologically confirmed hepatocellular carcinoma (HCC) or mixed HCC and cholangiocarcinoma either locally advanced or metastatic.
- Not a candidate for surgical resection, or transplant
Key exclusion criteria (20 listed)
- Hepatocelluar carcinoma (HCC) or other mixed subtype (fibrolamellar HCC, or sarcomatoid HCC) amenable to curative surgery or transplant
- Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements.
- Is pregnant or breastfeeding.
- Prior Abdominal radiation, including prior arterial Yttrium therapy.
- History of autoimmune disease.
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 |
|---|---|---|
| Stereotactic Body Radiation TreatmentSingle fraction SBRT 27 Gy | Radiation | Single fraction SBRT 27 Gy |
Primary outcome
Maximum tolerated dose (MTD) of Single Fraction GRID SBRT
Time frame: First day of post-GRID SBRT through 3 month post-radiation
Safely identify MTD of Single Fraction GRID SBRT and CTCAE v5.0 related toxicity: Irreversible grade 3 hepatotoxicity, grade 4 or 5 hepatotoxicity, grade 4 or 5 gastrointestinal toxicity.
5 secondary outcomes
Local control utilizing RECIST v1.1 for HCC.
Time frame: End of treatment through 3 month post-radiation
Regional failure utilizing RECIST v1.1 for HCC.
Time frame: End of treatment through 3 month post-radiation
Progression free survival (PFS)
Time frame: Enrollment through 3-months after end of immunotherapy treatment
Time to Progression (TTP)
Time frame: Enrollment through 3-months after end of immunotherapy treatment
Molecular correlatives: TCR repertoire analysis.
Time frame: Pre-vGRID vs Day 7-12 after vGRID (day 0) and 4-8 weeks after vGRID
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 24 Dec 2025.
- 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.
David Akhavan, MD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Body Radiation Treatment in people with Liver Cancer, run by University of Kansas Medical Center 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 20 inclusion and 20 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 24 Dec 2025. 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 Lauren Strider-Birkeness (913-945-6955, lstriderbirkeness@kumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of Single Fraction GRID SBRT (time frame: First day of post-GRID SBRT through 3 month post-radiation). 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 24 Dec 2025.