Proton vs Photon Therapy for Liver Cancer

Recruiting at 33 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Disqualifiers: Extrahepatic tumor, Uncontrolled malignancy, Pregnancy, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 3-4 weeks

186 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two types of radiation treatments to determine which is more effective for liver cancer patients: proton therapy and photon therapy (also known as X-ray therapy or external beam radiation therapy). Proton therapy may cause less damage to healthy organs, potentially improving survival rates. The trial seeks participants with liver cancer that cannot be surgically removed, who have up to three tumors, and at least one tumor that can be accurately measured. Participants will receive either proton or photon therapy and will undergo regular scans and blood tests throughout the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that systemic chemotherapy for the study cancer must not have been given within 2 weeks prior to registration, which might imply a need to pause certain treatments. It's best to discuss your specific medications with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that proton therapy holds promise for treating liver cancer with minimal side effects. Research indicates that high-dose proton therapy can effectively control tumors while causing little harm. Patients did not experience significant liver damage, even with higher radiation doses.

Photon therapy has also proven effective for liver cancer, but there are some differences. Photon therapy can affect nearby healthy liver tissue more than proton therapy because it uses x-rays, which can travel beyond the tumor.

Studies suggest that both treatments are generally safe and well-tolerated. Proton therapy may have an advantage in protecting healthy tissues, potentially leading to fewer side effects. However, both treatments have been used safely and have shown positive results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because proton therapy and photon therapy offer innovative approaches for treating liver cancer. Unlike traditional radiation therapies, proton therapy precisely targets cancer cells, potentially reducing damage to surrounding healthy tissue. This precision can lead to fewer side effects and improved patient outcomes. Photon therapy, while more widely used, is being studied for its effectiveness compared to proton therapy, helping to optimize treatment strategies for liver cancer. Both treatments aim to achieve better control of the disease with potentially fewer complications.

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

This trial will compare proton therapy and photon therapy for liver cancer. Studies have shown that proton therapy, one of the treatments in this trial, effectively controls liver tumors with few side effects. Research indicates that proton therapy stops precisely at the tumor, protecting healthy organs. In patients with liver cancer, this method has led to excellent long-term tumor control. Photon therapy, the other treatment option, uses x-rays to treat tumors and is commonly used for various cancers. It provides good control of liver tumors but may affect nearby healthy tissue more than proton therapy. Both treatments have shown promise, but proton therapy might better protect healthy organs. ^{1 2 3 4 6}

Who Is on the Research Team?

Theodore S Hong

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with liver cancer who have up to three tumors, meeting specific size requirements. They must have adequate organ function, may have had previous treatments like chemotherapy or surgery, and need a performance status showing they can carry out daily activities. Pregnant women or those not using contraception are excluded.

Inclusion Criteria

Negative urine or serum pregnancy test for women of childbearing potential within 7 days prior to study entry

ANC >= 1,000 cells/mm^3

Total bilirubin < 4 x institutional upper limit of normal

Exclusion Criteria

I have a history of cancer that is not currently under control.

I have had radiation therapy on the cancer area being studied.

I cannot confirm if my insurance covers the treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo proton or photon therapy over 15-24 days for 5 or 15 fractions, with CT scan, MRI, and blood sample collection throughout the study

3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months for 2 years, every 6 months for 3 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Photon Therapy
• Proton Therapy

Trial Overview The study compares two types of radiation therapy: photon therapy (high energy x-rays) and proton therapy (proton particles). Proton therapy might cause less damage to healthy organs around the tumor and potentially improve survival rates in liver cancer patients.

How Is the Trial Designed?

Group I: Arm II (photon therapy) Experimental Treatment 6 Interventions

Patients undergo photon therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.

Group II: Arm I (proton therapy) Experimental Treatment 6 Interventions

Patients undergo proton therapy over 15-24 days for 5 or 15 fractions. Patients undergo CT scan, MRI and blood sample collection throughout the study.

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

Approved in European Union as Photon Therapy for:

• Liver cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in United States as Photon Therapy for:

• Liver cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in Canada as Photon Therapy for:

• Liver cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in Japan as Photon Therapy for:

• Liver cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in China as Photon Therapy for:

• Liver cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Approved in Switzerland as Photon Therapy for:

• Liver cancer
• Breast cancer
• Lung cancer
• Prostate cancer
• Brain tumors

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 110 matched patients with hepatocellular carcinoma (HCC), proton radiotherapy demonstrated a significant survival benefit compared to photon radiotherapy, with a hazard ratio of 0.56 indicating better overall survival rates.

Proton therapy allowed for a higher biological equivalent dose of radiation while significantly reducing the risk of radiation-induced liver disease (RILD) to 11.8% compared to 36% in the photon group, suggesting a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton versus photon radiotherapy for primary hepatocellular carcinoma: a propensity-matched analysis. Cheng, JY., Liu, CM., Wang, YM., et al.[2021]

Proton beam therapy (PBT) is safer than X-ray therapy (XRT) for liver cancer treatment because it delivers a lower dose of radiation to surrounding healthy organs, which is crucial in reducing the risk of radiation-induced liver disease (RILD).

PBT has demonstrated excellent long-term tumor control with minimal toxicity in patients with hepatocellular carcinoma (HCC) and is increasingly being used effectively for unresectable cholangiocarcinoma and liver metastases, particularly for larger tumors that are not suitable for XRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for liver cancers. Chuong, M., Kaiser, A., Molitoris, J., et al.[2020]

Intensity modulated proton therapy (IMPT) showed a significant improvement in dose homogeneity (about 25%) and a 60% reduction in integral dose compared to volumetric modulated arc therapy (VMAT) in a study involving 20 patients with advanced hepatocellular carcinoma.

IMPT also demonstrated better sparing of organs at risk while maintaining target coverage, making it a promising treatment option, although careful management of positioning uncertainties is crucial to avoid potential underdosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of the potential role of intensity modulated proton therapy in the hypofractionated treatment of advanced hepatocellular carcinoma. Cozzi, L., Comito, T., Fogliata, A., et al.[2023]

Proton radiation therapy, particularly intensity-modulated proton therapy (IMPT), offers better dose localization compared to conventional photon radiation therapy, potentially reducing damage to surrounding healthy tissues in patients with head and neck and skull base tumors.

Initial clinical experiences suggest that IMPT may lead to fewer acute and long-term toxicities, and ongoing multi-institutional trials aim to further establish its effectiveness in treating these complex tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation therapy for head and neck cancer. Chan, AW., Liebsch, NJ.[2018]

Intensity-modulated proton therapy (IMPT) significantly reduces radiation exposure to organs at risk (OARs) compared to traditional stereotactic body radiation therapy (SBRT) in patients with liver metastases, as shown in a study involving 10 patients.

IMPT plans achieved similar target dose coverage while decreasing mean doses to critical organs like the liver, esophagus, kidneys, spinal cord, and lungs, indicating a safer treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric Comparison of Plans for Photon- or Proton-Beam Based Radiosurgery of Liver Metastases. Mondlane, G., Gubanski, M., Lind, PA., et al.[2022]

Proton beam radiotherapy (PBT) may offer advantages over traditional photon radiation for treating unresectable hepatocellular carcinoma (HCC) by better sparing healthy liver tissue, which is crucial since many patients have underlying liver disease.

The ongoing NRG Oncology GI003 trial is investigating whether PBT leads to improved clinical outcomes compared to photon therapy, highlighting the importance of optimizing treatment modalities for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton versus photon radiotherapy for hepatocellular carcinoma: Current data and technical considerations. Roberts, HJ., Hong, TS.[2023]

Charged particle therapy (CPT) significantly improves overall survival rates for hepatocellular carcinoma (HCC) patients compared to conventional radiotherapy (CRT), with higher survival rates at 1, 3, and 5 years based on a systematic review of 73 cohorts from 70 studies.

CPT also shows lower rates of high-grade acute and late toxicity compared to CRT and stereotactic body radiotherapy (SBRT), making it a safer option for treating HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: a systematic review and meta-analysis. Qi, WX., Fu, S., Zhang, Q., et al.[2022]

Intensity modulated proton beam therapy (IMPT) shows a clinically significant dosimetric advantage over intensity modulated photon therapy (IMRT) for esophageal cancer, particularly in sparing the heart and lungs, but both treatments resulted in similar acute toxicities and short-term clinical outcomes.

In a study of 64 patients, IMPT demonstrated comparable local control, progression-free survival, and overall survival rates to IMRT, indicating that IMPT is a safe and effective option for treating esophageal cancer, although longer follow-up is needed to fully assess its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Toxicities and Short-Term Patient Outcomes After Intensity-Modulated Proton Beam Radiation Therapy or Intensity-Modulated Photon Radiation Therapy for Esophageal Carcinoma: A Mayo Clinic Experience. Bhangoo, RS., DeWees, TA., Yu, NY., et al.[2022]

Pencil-beam scanning intensity modulated proton therapy (IMPT) for localized pancreatic cancer showed significant reductions in radiation exposure to surrounding organs at risk, such as the small bowel and liver, compared to volumetric modulated arc therapy (VMAT).

No patients experienced severe (grade ≥3) treatment-related adverse events, and there was no significant change in health-related quality of life scores during treatment, indicating that IMPT is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes. Jethwa, KR., Tryggestad, EJ., Whitaker, TJ., et al.[2022]

Proton therapy (IMPT) provides better dose distribution and sparing of healthy tissues compared to photon therapy (IMRT) for pediatric patients with intracranial tumors, particularly benefiting younger patients with supratentorial tumors.

Infratentorial tumors showed significant sparing of the optic chiasm with IMPT, while brainstem sparing was less pronounced, indicating that IMPT can effectively reduce radiation exposure to critical structures in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Target Location, Size, and Patient Age on Normal Tissue Sparing- Proton and Photon Therapy in Paediatric Brain Tumour Patient-Specific Approach. Dell'Oro, M., Short, M., Wilson, P., et al.[2020]

Intensity modulated proton therapy (IMPT) demonstrated a high local control rate of 94% and an overall survival rate of 78% in a study of 37 patients with hepatocellular carcinoma (HCC) over a median follow-up of 21 months.

The treatment was found to be safe, with only 3% of patients experiencing significant acute toxicity, and 16% showing a minor increase in liver function scores, indicating that IMPT is a feasible option for HCC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience. Bhangoo, RS., Mullikin, TC., Ashman, JB., et al.[2022]

Citations

1. redjournal.org redjournal.org/article/S0360-3016(23)07968-3/fulltext

Clinical and Dosimetric Results of Proton or Photon ... We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive ...

2. jgo.amegroups.org jgo.amegroups.org/article/view/28232/html

Proton beam therapy for liver cancers - Chuong High-dose PBT has been shown to achieve excellent long-term tumor control with minimal toxicity in hepatocellular carcinoma (HCC) patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10577334/

Current evidence and the potential role of proton beam ... PBT demonstrated an excellent local control rate reaching 85–95% and a comparable OS rate of more than 50% at 3–5 years after PBT in patients who received the ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301623079683

Clinical and Dosimetric Results of Proton or Photon ... Dosimetric analyses have suggested that proton radiation therapy provides greater sparing of normal tissues in patients with larger liver tumors, compared with ...

5. e-jlc.org e-jlc.org/journal/view.php?number=569

Recent update of proton beam therapy for hepatocellular ... The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other ...

6. practicalradonc.org practicalradonc.org/article/S1879-8500(21)00233-2/fulltext

External Beam Radiation Therapy for Primary Liver Cancers Prospective data support the use of palliative EBRT to help alleviate pain in patients with HCC and symptomatic liver lesions. A phase II trial ...