Radiation Therapy for Liver Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Unstable angina, Congestive heart failure, 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: 4

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and the best dose of radiation therapy in treating patients with hepatocellular carcinoma, cholangiocarcinoma, or cancer that has spread from the original (primary) tumor to the liver who also have impaired liver function (liver damage caused by cirrhosis, chemotherapy, or surgery). Radiation therapy (RT) uses high energy x-rays to kill tumor cells and shrink tumors. New methods of giving RT to the liver may help control cancer.

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, you may be allowed to continue taking capecitabine or sorafenib during the trial, as decided by your doctor.

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

Research shows that advanced radiation techniques like stereotactic body radiotherapy (SBRT) can control liver cancer effectively, with local control rates as high as 90%. These methods allow precise targeting of the tumor, sparing healthy liver tissue and potentially improving outcomes for patients who cannot undergo surgery. ^{1 2 3 4 5}

Is radiation therapy generally safe for humans?

Radiation therapy, including advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), has been shown to be generally safe in humans, with some risk of side effects. Studies have reported low rates of serious side effects, such as gastrointestinal and genitourinary toxicities, especially when using advanced techniques that help protect normal tissues. ^{6 7 8 9 10}

How is radiation therapy unique for treating liver cancer?

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 minimizing damage to healthy liver tissue. These methods allow for effective treatment of liver tumors that were previously difficult to reach, with promising response rates and manageable side effects. ^{2 4 11 12 13}

Research Team

Eugene J. Koay

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with liver cancer, bile duct cancer, or tumors that have spread to the liver and also have impaired liver function. Participants must have at least 400 ml of functional liver tissue and an ECOG performance status of 0-2. Women who can bear children should use contraception and not breastfeed. Those with recent heart issues, active hepatitis, infections, inflammatory bowel disease or another active malignancy are excluded.

Inclusion Criteria

Signed study-specific consent form

I had liver radiation therapy over 6 months ago for Y90 or over 12 months for others.

I have one or more tumors.

Exclusion Criteria

I currently have a fever or an untreated infection.

I do not have active hepatitis.

My inflammatory bowel disease is not well-managed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo radiation therapy 5 days a week for a total of 15 or 25 fractions in the absence of disease progression or unacceptable toxicity

3-5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Follow-up at 4-8 weeks, then every 3-4 months for 2 years

Treatment Details

Interventions

• Radiation Therapy

Trial Overview The study is testing different doses of radiation therapy to find the safest and most effective dose for patients with specific types of liver cancers and compromised liver function. It includes biomarker analysis, MRI scans, surveys on health status, alongside the radiation treatment.

Participant Groups

Group I: Treatment (radiation therapy) Experimental Treatment 4 Interventions

Patients undergo radiation therapy 5 days a week for a total of 15 or 25 fractions in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a study of 22 patients with locally advanced rectal cancer, image-guided radiotherapy (IGRT) led to complete surgical resection in all cases, with 32% of patients showing no residual tumor after treatment.

The treatment was associated with minimal toxicity, although one patient experienced severe side effects likely due to an overdose of capecitabine, suggesting that IGRT is a promising approach for reducing complications in rectal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of image-guided radiotherapy for locally advanced rectal cancer. Nguyen, NP., Ceizyk, M., Almeida, F., et al.[2011]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

In a study of 260 men with localized prostate cancer treated with high-dose IGRT and IMRT, the combination resulted in a low rate of late toxicity, with only 4.4% experiencing grade 2 gastrointestinal issues and 7.1% with grade 2 genitourinary issues after 7 years.

The treatment showed high efficacy, with a 7-year prostate-specific antigen relapse-free survival rate of 97.1% for low-risk patients, indicating that this approach is both safe and effective for managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. Doležel, M., Odrážka, K., Vaňásek, J., et al.[2021]

In a study of 658 patients with high-risk endometrial cancer, intensity-modulated radiation therapy (IMRT) was associated with significantly fewer grade ≥2 adverse events, such as diarrhea and hematologic issues, compared to 3-dimensional conformal radiation therapy (3DCRT) during follow-up.

IMRT also showed a trend towards fewer patient-reported symptoms like bowel urgency and abdominal cramps during treatment, indicating it may provide a better quality of life for patients undergoing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy. Wortman, BG., Post, CCB., Powell, ME., et al.[2022]

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]

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]

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]

References

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

Image-guided radiotherapy for liver cancer using respiratory-correlated computed tomography and cone-beam computed tomography. [2022]

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

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review. [2005]

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

Effectiveness of image-guided radiotherapy for locally advanced rectal cancer. [2011]

4. England pubmed.ncbi.nlm.nih.gov

Radiation therapy for intrahepatic malignancies. [2009]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Brief Overview. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. [2018]

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

9. Czech Republic pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. [2021]

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

Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy. [2022]

11. France pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy and selective internal radiation therapy for hepatocellular carcinoma. [2011]

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

Radiation oncology approaches in liver malignancies. [2018]

13. England pubmed.ncbi.nlm.nih.gov

An international survey on liver metastases radiotherapy. [2015]