Standard vs Targeted Radiation Therapy for Liver Cancer

(SAVIOR Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Michael Lock, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Disqualifiers: Severe cirrhosis, Prior radiotherapy, Active hepatitis, others

No Placebo Group

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

Radiation is a standard treatment option for patients with liver cancer. Unfortunately, the tumour grows after radiation in many patients and radiation can harm normal tissues. A new treatment using a specialized radiation procedure called Stereotactic body radiotherapy (SBRT) may increase the chance to control liver cancer and reduce the chance of harm to normal tissues. SBRT allows radiation treatments to be focused more precisely, and be delivered more accurately than with older treatments. SBRT has become a routine treatment. Further research has found that specialized computer programs can possibly guide the selection of an appropriate SBRT dose. This is called radiobiological guidance. However, this has not yet been proven to improve outcomes and/or reduce toxicity. Therefore, the purpose of this study is to find out if SBRT at standard dose versus SBRT guided by radiobiological techniques is better for you and your liver cancer.

Will I have to stop taking my current medications?

The trial requires that multikinase inhibitors be stopped 2 weeks before radiation and can be restarted 1 week after. Chemotherapy must be completed at least 2 weeks before radiation and not planned for at least 1 week after treatment (4 weeks for anthracyclines).

What data supports the effectiveness of this treatment for liver cancer?

Research shows that modern radiation therapy techniques, like stereotactic body radiotherapy (SBRT) and proton beam therapy (PBT), are effective in treating liver cancer, with response rates between 50% to 97%. These methods allow precise targeting of tumors while sparing healthy liver tissue, making them a promising option for liver cancer treatment.

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Is radiation therapy generally safe for treating liver cancer?

Radiation therapy for liver cancer is generally considered safe, with serious complications being rare. Most side effects are mild, and modern techniques allow precise targeting of tumors while sparing healthy liver tissue.

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How does radiation therapy for liver cancer differ from other treatments?

Radiation therapy for liver cancer is unique because it uses advanced techniques like stereotactic body radiotherapy (SBRT) and proton beam therapy (PBT) to precisely target tumors while sparing healthy liver tissue. These methods allow for effective treatment of liver tumors that were previously difficult to reach, with fewer side effects compared to traditional radiation methods.

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Eligibility Criteria

This trial is for adults with liver cancer that can't be removed by surgery. It's open to those with primary liver cancer or certain types of liver metastases, up to 5 measurable lesions, and a life expectancy over 6 months. Patients must not have severe illnesses limiting life span under 6 months, active hepatitis, severe cirrhosis (Child Pugh >B7), or prior overlapping radiation therapy.

Inclusion Criteria

My condition cannot be treated with surgery.

I stopped taking multikinase inhibitors 2 weeks before radiation and can restart 1 week after.

I am older than 18 years.

Exclusion Criteria

My liver condition is not severe (Child Pugh ≤B7).

My life expectancy is more than 6 months despite my other health issues.

I've had radiation in the same area where my current cancer is located.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either standard dose or personalized dose SBRT, delivered in 5 fractions every other day excluding weekends and holidays

2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and progression of disease

6 months

1 month post-treatment, 3 months post-treatment, every 3 months up to 5 years

Long-term follow-up

Participants' overall survival and quality of life are assessed

Up to 5 years

Participant Groups

The study compares standard dose SBRT versus radiobiologically-guided SBRT in treating liver cancer. The goal is to see if the guided approach better controls the cancer while reducing harm to healthy tissues compared to the standard treatment.

Group I: Personalized Dose Selection Radiation Experimental Treatment 1 Intervention

Patients in the experimental arm will receive individually selected prescription dose guided by radiobiological parameters described below, preferably delivered in 5 fractions every other day, excluding weekends and holidays. Volumetric-modulated arc therapy (VMAT) is the preferred planning technique. Typical planning uses 2 arcs, \<=10MV and FFF mode where possible as almost all liver treatments are gated). In the event of multiple lesions, multiple isocentres are allowed. Often lateral isocentre shifts are significant and therefore arc ranges should be chosen to minimize collision risk. Treatment will be every second day excluding weekends and holidays.

Group II: Standard Dose Radiation Active Control 1 Intervention

Patients in the standard arm will receive a standard dose of 2000cGy in 5 fractions using simple CT planning. IMRT is allowed. Treatment will be every second day excluding weekends and holidays.

Radiation therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺 Approved in European Union as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

🇺🇸 Approved in United States as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Cervical cancer
• Uterine cancer

🇨🇦 Approved in Canada as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

🇯🇵 Approved in Japan as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Esophageal cancer

🇨🇳 Approved in China as Radiotherapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer
• Nasopharyngeal cancer

🇨🇭 Approved in Switzerland as Radiation therapy for:

• Breast cancer
• Lung cancer
• Colorectal cancer
• Prostate cancer
• Brain tumors
• Skin cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

London Regional Cancer Program London, Canada

Who Is Running the Clinical Trial?

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's Lead Sponsor

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's Lead Sponsor

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's Lead Sponsor

Lawson Health Research Institute Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Radiation oncology approaches in liver malignancies. [2018] Radiation therapy plays an increasingly important role in the treatment of hepatic malignancies. There is convincing evidence of safety and efficacy employing brachytherapy (yttrium-90), three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy (SBRT), and proton beam therapy (PBT) in all stages of primary and metastatic involvement in the liver. Technologic advances in tumor imaging, real-time tracking of moving targets during radiotherapy delivery, and superb radiation dose deposition control have enabled treatment of previously unapproachable lesions. Recently completed and ongoing clinical trials are refining optimal dose fractionation schedules for SBRT as monotherapy. Radioembolization as part of first-line therapy in metastatic colorectal tumors is being tested in large international trials combined with FOLFOX6 and bevacizumab, as well as in hepatocellular carcinoma with sorafenib. PBT is becoming more available as new facilities open in many countries providing particle beam therapy, which delivers unparalleled control of radiation dose close to critical structures. A major point of research is understanding how best to safely destroy tumors in the background of often fragile hepatic function from cirrhosis or heavily pretreated chemotherapy liver parenchyma. Fortunately, serious complications from radiotherapy are rare, acute toxicities are typically Common Terminology Criteria for Adverse Events v4.0 grade 1-2, with consistent response rates of 50% to 97% in the modern era.

2. United States pubmed.ncbi.nlm.nih.gov

Ablative radiotherapy for colorectal liver metastases and intrahepatic cholangiocarcinoma. [2023] The role of radiation therapy in the management of liver cancers, both primary and metastatic, has changed drastically over the past several decades. Although conventional radiation was limited by technology, the advent of advanced image-guided radiotherapy and the rise in evidence for and popularity of stereotactic body radiotherapy have expanded the indications for radiation in these two distinct disease types. Magnetic resonance imaging-guided radiation therapy, daily online adaptive radiotherapy, and proton radiotherapy are some of many modern radiotherapy techniques that allow for increasingly efficacious treatment of intrahepatic disease while simultaneously allowing for increased normal tissue sparing, including sparing of the normal liver and the radiosensitive luminal gastrointestinal tract. Modern radiation therapy should be considered along with approaches such as surgical resection and radiofrequency ablation for the management of liver cancers of diverse histologies. Herein we describe the use of modern radiotherapy in two example settings, colorectal liver metastases and intrahepatic cholangiocarcinoma, and how external beam radiotherapy provides options within multidisciplinary discussions to elect optimal patient-specific treatments.

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Stereotactic ablative radiotherapy for hepatocellular carcinoma: History, current status, and opportunities. [2018] A variety of surgical and other local-regional approaches to the management of hepatocellular carcinoma (HCC) are in clinical use. External beam radiation therapy is a relative newcomer to the portfolio of treatment options. Advances in planning and delivery of radiation therapy, developing in parallel with and inspiring changing paradigms of tumor management in the field of radiation oncology, have led to growing interest in radiation therapy as a viable treatment option for HCC as well as other liver tumors. In this review, we discuss these advances, current trends in liver radiotherapy, as well as avenues of future clinical and basic research. Liver Transplantation 24 420-427 2018 AASLD.

4. United States pubmed.ncbi.nlm.nih.gov

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review. [2005] The limited efficacy of current approaches to the treatment of patients with hepatic cancer, including external beam radiation therapy and cytotoxic chemotherapy, has reawakened interest in the use of internal radiation therapy.

5. United States pubmed.ncbi.nlm.nih.gov

Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. [2020] Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC.

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Selective internal radiation therapy in the management of primary and metastatic disease in the liver. [2021] Selective internal radiation therapy is a type of brachytherapy used to provide targeted radiotherapy, most commonly to treat primary or metastatic disease within the liver. This review outlines current clinical practice, dosimetric considerations, the pre-treatment workup and safety considerations before treatment. It also examines the clinical evidence for its use in patients with both primary and metastatic disease within the liver.

7. France pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy and selective internal radiation therapy for hepatocellular carcinoma. [2011] Recent technological advances allow precise and safe radiation delivery in hepatocellular carcinoma. Stereotactic body radiotherapy is a conformal external beam radiation technique that uses a small number of relatively large fractions to deliver potent doses of radiation therapy to extracranial sites. It requires stringent breathing motion control and image guidance. Selective internal radiotherapy or radioembolization refers to the injection of radioisotopes, usually delivered to liver tumors via the hepatic artery. Clinical results for both treatments show that excellent local control is possible with acceptable toxicity. Most appropriate patient populations and when which type of radiation therapy should be best employed in the vast therapeutic armamentarium of hepatocellular carcinoma are still to be clarified.

8. United States pubmed.ncbi.nlm.nih.gov

External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy. [2022] External beam radiotherapy has historically played a minor role in the primary treatment of hepatocellular carcinoma. Although there is evidence for tumor response to external beam radiotherapy and despite the fact that a radiation dose-response relationship has been established, the limited radiation tolerance of the adjacent normal liver has prohibited wider use of radiation therapy in this disease. Recent technological and conceptual developments in the field of radiation therapy-such as intensity-modulated radiation therapy, image-guided radiation therapy, and stereotactic body radiation therapy-have the potential to improve radiation treatments by conforming the delivered radiation dose distribution tightly to the tumor or target volume outline while sparing normal liver tissue from high-dose radiation. Image guidance allows for a reduction of added (normal tissue) safety margins designed to account for interfraction patient and target setup variability, and stereotactic targeting will further reduce residual target setup uncertainty. Combining improvements in tumor targeting with normal tissue sparing, radiation dose delivery will enable clinically effective and safe radiation delivery for liver tumors such as hepatocellular carcinoma. This article reviews the role of radiotherapy for hepatocellular carcinoma; presents modern radiation therapy modalities and concepts such as intensity-modulated, image-guided, and stereotactic body radiation therapy; and hypothesizes about their future effect on primary treatment alternatives.

9. United States pubmed.ncbi.nlm.nih.gov

Radiation therapy for hepatocellular carcinoma. [2022] Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, and its incidence is on the rise. The primary therapy is resection or liver transplant, but only a minority of patients present with resectable disease. Historically, radiotherapy has not played a significant role in the treatment of liver malignancies because of the low tolerance of the whole liver to radiation. With improvements in 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy, higher doses of radiation can be delivered to target lesions with low doses to the noninvolved liver; thus, experience in the use of radiation for the treatment of focal HCC has increased. At the same time, our understanding of the relationships between radiation dose and volume and the risk of classic radiation-induced liver disease and other toxicities more likely to occur in HCC patients has improved considerably. These developments have led to a body of evidence that now supports the careful use of radiotherapy for unresectable HCC. The rationale for studying radiotherapy in a randomized trial is strong.

10. England pubmed.ncbi.nlm.nih.gov

An international survey on liver metastases radiotherapy. [2015] An international survey of radiation therapy (RT) of liver metastases was undertaken by the Liver Cancer Workgroup of the Third International Consensus on Metastases Workshop at the 2010 American Society for Radiation Oncology (ASTRO) meeting.