SBRT for Liver Cancer

(vGRID SBRT Trial)

Overseen By Lauren Strider-Birkeness

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Kansas Medical Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Autoimmune disease, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safe radiation levels for treating liver cancer using a new technique called vGRID (Stereotactic Body Radiation Therapy). The researchers aim to find the highest tolerable dose while managing side effects, with the hope of improving treatment outcomes. Individuals with liver cancer that cannot be removed through surgery or transplant may be suitable candidates, particularly if the cancer has spread or is too advanced. The trial seeks participants who can safely join without facing certain risks, such as prior abdominal radiation or uncontrolled additional illnesses.

As an unphased trial, this study provides patients with access to innovative treatment options that could potentially enhance their quality of life.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using immunosuppressive drugs like corticosteroids or TNF-alpha blockers, you may not be eligible to participate. It's best to discuss your current medications with the trial team.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using immunosuppressive drugs like corticosteroids, you may not be eligible to participate. It's best to discuss your specific medications with the trial team.

What prior data suggests that the vGRID therapy technique is safe for liver cancer?

Research has shown that vGRID therapy was safe in earlier studies. One study found that a single dose of 30 Gy (a unit of radiation) was safe for treating liver tumors. This suggests that vGRID therapy might be well-tolerated, even at higher doses being tested.

Other research has found that similar radiation treatments for liver cancer have low rates of serious side effects, meaning patients experienced fewer severe reactions. These findings suggest that vGRID therapy is likely safe for participants, based on evidence from similar treatments in other studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about vGRID SBRT for liver cancer because it offers a unique, single-day treatment approach. Unlike traditional treatments that often require multiple sessions over several weeks, vGRID utilizes a single fraction of stereotactic body radiation therapy (SBRT) at 27 Gy, which can be completed in just one day. This innovative method not only aims to reduce the overall treatment time but also potentially minimizes side effects typically associated with prolonged radiation exposure. By streamlining the treatment process, vGRID SBRT holds promise for greater convenience and improved patient outcomes.

What evidence suggests that vGRID therapy might be an effective treatment for liver cancer?

Research has shown that stereotactic body radiation therapy (SBRT) effectively treats liver cancer. This radiation therapy targets tumors with high doses while protecting nearby healthy tissue. Studies have demonstrated that a single dose of SBRT up to 30 Gy is safe for liver tumors, though larger tumors might require higher doses. This trial tests the vGRID technique, which has shown low side effects and high effectiveness in other cancers, even with very high radiation doses. These findings suggest that vGRID could be a promising treatment for liver cancer, allowing for higher radiation doses with manageable side effects. ^{1 2 3 5 6}

Who Is on the Research Team?

David Akhavan

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with unresectable or metastatic hepatocellular carcinoma (liver cancer) who have adequate blood counts, liver and kidney function, and are not pregnant. They must agree to use contraception and cannot be eligible for a transplant or have severe active comorbidities like heart failure, uncontrolled bleeding, or infections.

Inclusion Criteria

I, or my legal representative, can understand the study and agree to sign the consent form.

I agree not to donate sperm during and for 12 months after the study.

My liver cancer is confirmed and has spread or is advanced.

Exclusion Criteria

My liver cancer is operable or suitable for a transplant.

Severe active co-morbidities

I will not donate blood during or after the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive vGRID SBRT radiation therapy with dose escalation to determine the maximum tolerated dose

1 day

1 visit (in-person)

Immunotherapy Treatment

Participants begin standard of care treatment with Atezolizumab 12-16 days after radiation

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• vGRID

Trial Overview The trial is testing the maximum tolerated dose of Stereotactic Body Radiation Treatment (SBRT) using vGRID therapy technique on liver tumors. It aims to find out how much radiation can be given safely while monitoring the side effects.

How Is the Trial Designed?

Group I: Single fraction SBRT 27 Gy Experimental Treatment 1 Intervention

vGRID SBRT 3+3 dose escalation, single fraction, one day cycle length

vGRID is already approved in United States, European Union for the following indications:

Approved in United States as vGRID SBRT for:

• Unresectable or metastatic hepatocellular carcinoma (HCC)

Approved in European Union as vGRID SBRT for:

• Unresectable or metastatic hepatocellular carcinoma (HCC)

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Varian

Collaborator

Trials

5

Recruited

380+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

Stereotactic body radiotherapy (SBRT) shows promise for treating tumors of the liver hilum, such as pancreatic cancer and Klatskin tumors, with local tumor control rates around 80% over 24 months.

Recent advancements in SBRT techniques, particularly image-guided radiotherapy (IGRT), have significantly reduced severe side effects (grade 3 and 4 toxicities) to less than 10%, compared to higher toxicity rates seen with older methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiotherapy in the liver hilum. Basis for future studies. Zamboglou, C., Messmer, MB., Becker, G., et al.[2021]

In a study involving 56 patients treated with Magnetic Resonance guided Radiotherapy (MRgRT) for primary liver tumors, no severe toxicities (greater than CTCAE grade 2) were observed, indicating a high safety profile for this treatment.

MRgRT achieved excellent local control rates of 98.1% at 12 months and 94.7% at 18 months, with an overall survival rate of 85.1% at 1 year, demonstrating its efficacy in managing primary liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective registry study of stereotactic magnetic resonance guided radiotherapy (MRgRT) for primary liver tumors. Bordeau, K., Michalet, M., Dorion, V., et al.[2023]

In a study of 30 patients undergoing stereotactic body radiation therapy (SBRT) for liver cancer, significant variations in the dose delivered to adjacent organs at risk (OARs) were observed, particularly for the stomach, heart, and esophagus, which could lead to potential toxicity.

The study identified that most dose discrepancies were due to craniocaudal shifts in organ position, highlighting the importance of daily imaging and adaptive replanning to minimize risks to OARs during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Dosimetric Impact of Interfractional Organ-at-Risk Movement During Liver Stereotactic Body Radiation Therapy. Schmid, RK., Tai, A., Klawikowski, S., et al.[2020]

In a study of 66 patients with inoperable hepatocellular carcinoma (HCC) treated with image-guided liver stereotactic body radiation therapy (SBRT), there was a 100% local control rate and overall survival of 83.9% at one year, indicating high efficacy of this treatment.

The treatment was found to be safe, with no patients experiencing grade 3 toxicity, although one patient did develop a grade 4 gastric ulcer; this suggests that while SBRT is effective, careful monitoring is necessary to manage potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-Guided Liver Stereotactic Body Radiotherapy Using VMAT and Real-Time Adaptive Tumor Gating: Evaluation of the Efficacy and Toxicity for Hepatocellular Carcinoma. Cantaloube, M., Castan, F., Creoff, M., et al.[2021]

In a study of 51 patients treated with online MR-guided stereotactic body radiotherapy (SBRT) for liver metastases, the treatment demonstrated a high local control rate of 89.6% after 12 months, indicating its efficacy in managing liver tumors.

The treatment was well-tolerated with no acute grade ≥ 3 toxicities reported, and patient quality of life remained stable, suggesting that MRgRT is a safe and noninvasive option for patients with liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local control and patient reported outcomes after online MR guided stereotactic body radiotherapy of liver metastases. Uder, L., Nachbar, M., Butzer, S., et al.[2023]

Stereotactic body radiotherapy (SBRT) is a safe and effective treatment for early-stage Hepatocellular carcinoma (HCC), with no significant complications reported in a study of 23 patients, and it can serve as a bridge to liver transplantation.

Among the transplanted patients, the median overall survival was not reached after 12 months of follow-up, indicating promising long-term outcomes, while 27.3% of liver explants showed a complete pathological response post-SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy (SBRT) for definitive treatment and as a bridge to liver transplantation in early stage inoperable Hepatocellular carcinoma. Moore, A., Cohen-Naftaly, M., Tobar, A., et al.[2022]

Stereotactic body radiotherapy (SBRT) is a safe and effective treatment for both primary liver tumors and liver metastases, with low associated morbidity.

The guidelines developed by the Working Group on Stereotactic Radiotherapy include recommendations for patient selection, treatment planning, and dose constraints to protect critical organs, ensuring optimal treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for liver tumors: principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy. Sterzing, F., Brunner, TB., Ernst, I., et al.[2022]

Automated daily plan reoptimization in liver stereotactic body radiation therapy (SBRT) significantly reduces the risk of exceeding dose limits for nearby organs at risk, with violations dropping from 1-6 Gy to less than 1 Gy in most cases.

Reoptimizing both beam profiles and angles provided the best results for dose delivery, although reoptimizing only beam profiles was much quicker, taking only a few minutes compared to several hours for full reoptimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive liver stereotactic body radiation therapy: automated daily plan reoptimization prevents dose delivery degradation caused by anatomy deformations. Leinders, SM., Breedveld, S., Méndez Romero, A., et al.[2018]

The study evaluated the effectiveness of single-isocentre versus multi-isocentre volumetric-modulated arc therapy (VMAT) for treating multiple liver metastases in 30 patients, finding that while the single-isocentre technique reduced treatment time and improved patient comfort, it resulted in a slightly higher mean liver dose (MLD) compared to the multi-isocentre approach.

RapidPlan-based automatic planning (RPS and RPM) showed slight improvements in liver dose sparing and reduced complications compared to manual planning, although they increased monitor units and delivery time, indicating a trade-off between planning quality and efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and dosimetric evaluation of single- and multi-isocentre stereotactic body radiation therapy for multiple liver metastases. Tang, C., Gong, C., Liu, B., et al.[2023]

In a study involving 47 liver cancer patients, the use of implanted fiducial markers and intrafraction kV imaging during gated volumetric modulated arc therapy (VMAT) showed that tumor repositioning was effectively monitored, with a mean deviation of only 1.0 mm during treatment.

The results indicated that in 99% of cases, fiducial marker deviations were within 4.5 mm, which is well within the 5 mm treatment margin, suggesting that the gated VMAT SBRT technique is safe and effective for liver cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of reproducibility of tumor repositioning during multiple breathing cycles for liver stereotactic body radiotherapy treatment. Bedos, L., Riou, O., Aillères, N., et al.[2022]

In a study involving 10 patients with liver metastases, MR-guided stereotactic body radiotherapy (MRgSBRT) demonstrated excellent visibility of tumors without the need for fiducial markers, indicating a promising non-invasive treatment option.

The treatment was well-accepted by patients, with no reported cases of symptomatic radiation-induced liver disease after a median follow-up of 10 months, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marker-less online MR-guided stereotactic body radiotherapy of liver metastases at a 1.5 T MR-Linac - Feasibility, workflow data and patient acceptance. Gani, C., Boeke, S., McNair, H., et al.[2022]

In a study of 74 hepatocellular carcinoma (HCC) patients treated with robotic stereotactic body radiation therapy (SBRT), 13 patients experienced significant hepatic adverse reactions, indicating potential safety concerns with this treatment.

The study identified that having a total liver volume greater than 1,162 mL and a normal liver volume greater than 1,148 mL are important factors that can help reduce the risk of severe liver reactions after SBRT, suggesting that careful patient selection is crucial for improving treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the factors affecting the safety of robotic stereotactic body radiation therapy for hepatocellular carcinoma patients. Liu, X., Song, Y., Liang, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05727787

Study Details | NCT05727787 | vGRID SBRT: A Phase I ... 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.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05315

Virtual GRID Stereotactic Body Radiation Therapy for the ... This clinical trial tests the safety, side effects, and best dose of virtual GRID (vGRID) stereotactic body radiation therapy (SBRT) in treating patients ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/424915

vGRID SBRT: A Phase I Clinical Trial in Unresectable or ... This trial will provide the maximum tolerated dose for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7340168/

Long term outcomes of Stereotactic Body Radiation Therapy ... This report aimed to address the limited availability of long-term outcomes post SBRT for HCC from North America.

5. withpower.com withpower.com/trial/sbrt-for-liver-cancer-81458

SBRT for Liver Cancer (vGRID SBRT Trial) Research shows that stereotactic body radiation therapy (SBRT) is effective for treating liver cancer, and improvements in planning and delivery techniques ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37597757/

Stereotactic Body Radiation Therapy for Hepatocellular ... This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined ...