Standard vs Targeted Radiation Therapy for Liver Cancer

(SAVIOR Trial)

Overseen By Morgan Black

Age: 18+

Sex: Any

Trial Phase: Academic

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

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

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 2 weeks

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat liver cancer using Stereotactic Body Radiotherapy (SBRT), a specialized radiation technique. The researchers aim to determine if SBRT, guided by advanced computer programs to adjust the dose, is more effective and safer than the standard radiation therapy dose. This approach could better control the cancer and reduce harm to normal tissues. Suitable participants have liver cancer that cannot be surgically removed and up to five measurable liver tumors. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance future liver cancer treatments.

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 prior data suggests that Stereotactic body radiotherapy (SBRT) is safe for liver cancer treatment?

Studies have shown that Stereotactic Body Radiotherapy (SBRT) is generally well-tolerated for treating liver cancer. Research indicates that SBRT has a high success rate, with over 90% effectiveness in targeting liver tumors, meaning the procedure effectively focuses radiation on cancer cells.

SBRT is a specialized radiation treatment that allows precise targeting, protecting healthy tissues. This trial tests a personalized approach to determine the best radiation dose for each patient, based on specific medical factors, to improve safety and effectiveness. While this personalized method remains under study, using SBRT for liver cancer is common and has proven safe.

Overall, evidence suggests that SBRT, whether standard or personalized, is a safe option for liver cancer patients. However, like any treatment, some risks may still exist, and discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the potential of personalized radiation doses for liver cancer, which could revolutionize treatment. Unlike standard care that uses a fixed radiation dose, the experimental approach tailors the dose based on individual radiobiological parameters. This personalized method aims to maximize effectiveness while minimizing side effects. By using advanced techniques like volumetric-modulated arc therapy (VMAT), the treatment is more precise, potentially improving outcomes for patients with liver cancer.

What evidence suggests that this trial's radiation therapy treatments could be effective for liver cancer?

Research has shown that Stereotactic Body Radiotherapy (SBRT) effectively controls tumor growth in liver cancer with few side effects. Studies have found high success rates in controlling cancer and improving survival when SBRT is used for early to intermediate stages of liver cancer. In this trial, participants will join different treatment arms. One arm will receive a personalized dose of radiation therapy, customizing the treatment based on individual needs to potentially improve outcomes. Early results suggest that personalized SBRT offers excellent control of liver tumors, making it a promising treatment option. This method aims to deliver the right dose for better results while minimizing damage to healthy tissues. ^{1 2 3 6 7}

Who Is on the Research Team?

Michael Lock, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Radiation therapy

Trial Overview

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

668

Recruited

424,000+

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

Lead Sponsor

Trials

678

Recruited

421,000+

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

Lead Sponsor

Trials

686

Recruited

427,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Published Research Related to This Trial

Modern radiation therapy techniques, such as image-guided radiotherapy and stereotactic body radiotherapy, have significantly improved the treatment of liver cancers by allowing for more effective targeting of tumors while protecting healthy tissue.

These advancements in radiation therapy should be considered alongside traditional treatments like surgery and radiofrequency ablation, providing a comprehensive approach to managing various types of liver cancer, including colorectal liver metastases and intrahepatic cholangiocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ablative radiotherapy for colorectal liver metastases and intrahepatic cholangiocarcinoma. Schiff, JP., D'Souza, A., Henke, LE.[2023]

High dose rate interstitial irradiation with (192)Ir showed promising results, achieving local control of hepatic metastases for a median of 8 months and complete tumor eradication in 2 patients.

Direct intratumoral injection of 90Y microspheres was highly effective, reducing the size of 90.6% of tumors and completely destroying them in 8 patients, indicating a potential for targeted treatment in liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review. Ho, S., Lau, WY., Leung, TW., et al.[2005]

Stereotactic body radiotherapy and selective internal radiotherapy (radioembolization) are advanced techniques that provide precise and safe radiation delivery for treating hepatocellular carcinoma, showing excellent local control with acceptable toxicity.

Further research is needed to determine the most suitable patient populations and the optimal timing for using these radiation therapies in the treatment of liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy and selective internal radiation therapy for hepatocellular carcinoma. Bujold, A., Dawson, LA.[2011]

An international survey involving 69 radiation therapy professionals revealed a significant increase (36%) in referrals for liver metastases treatment over the past five years, indicating a growing demand for radiation therapy in this area.

The survey highlighted a lack of uniformity in treatment approaches, with various dose regimens and technologies being used, suggesting the need for prospective studies to optimize patient selection and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on liver metastases radiotherapy. Lock, MI., Hoyer, M., Bydder, SA., et al.[2015]

Radiation therapy, including techniques like brachytherapy and stereotactic body radiotherapy (SBRT), is safe and effective for treating liver cancers, with response rates ranging from 50% to 97% in recent studies.

Technological advancements in imaging and radiation delivery have improved the ability to treat difficult-to-reach tumors while minimizing damage to surrounding healthy tissue, making these therapies increasingly viable for patients with compromised liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation oncology approaches in liver malignancies. Kennedy, AS.[2018]

External beam radiation therapy is emerging as a promising treatment option for hepatocellular carcinoma (HCC) due to advancements in planning and delivery techniques.

The review highlights the growing interest in radiation therapy for liver tumors and suggests that ongoing research may further enhance its effectiveness and integration into treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for hepatocellular carcinoma: History, current status, and opportunities. Meyer, J., Singal, AG.[2018]

Selective internal radiation therapy (SIRT) is an effective targeted treatment for both primary and metastatic liver diseases, utilizing brachytherapy to deliver radiation directly to the tumor.

The review emphasizes the importance of thorough pre-treatment workup and safety considerations to optimize patient outcomes and minimize risks associated with this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective internal radiation therapy in the management of primary and metastatic disease in the liver. Preston, E., Shaida, N.[2021]

Recent advancements in 3-dimensional conformal and intensity-modulated radiotherapy allow for higher doses of radiation to be safely delivered to hepatocellular carcinoma (HCC) lesions while minimizing exposure to healthy liver tissue.

These improvements in radiotherapy techniques, along with a better understanding of radiation dose relationships and risks, support the potential for effective treatment of unresectable HCC, warranting further investigation through randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy for hepatocellular carcinoma. Feng, M., Ben-Josef, E.[2022]

In a study of 133 patients with unresectable hepatocellular carcinoma (HCC), proton radiation therapy significantly improved overall survival compared to photon therapy, with median survival times of 31 months for protons versus 14 months for photons.

Proton therapy also reduced the risk of non-classic radiation-induced liver disease, which is linked to worse survival outcomes, suggesting that proton therapy may help prevent liver decompensation after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. Sanford, NN., Pursley, J., Noe, B., et al.[2020]

Recent advancements in radiation therapy techniques, such as intensity-modulated and stereotactic body radiation therapy, allow for more precise targeting of liver tumors while minimizing damage to surrounding healthy liver tissue.

These innovations could enhance the safety and efficacy of external beam radiotherapy for treating hepatocellular carcinoma, which has historically been limited due to the sensitivity of normal liver tissue to radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy. Fuss, M., Salter, BJ., Herman, TS., et al.[2022]

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