Proton Radiation for Esophageal Cancer

Overseen By Proton Referral Office First call: Referral Office intake personnel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Loma Linda University

Disqualifiers: Cervical esophageal carcinoma, T1N0, T4, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan for esophageal cancer, combining proton radiation (also known as proton beam therapy or proton therapy) with two chemotherapy drugs, carboplatin and paclitaxel. Proton radiation may target tumors more precisely than traditional x-rays, potentially reducing side effects. The study aims to determine if this combination is more effective and less toxic than the usual treatment. It seeks participants with specific types of esophageal cancer, particularly those involving the mid or lower esophagus or the top part of the stomach. Individuals diagnosed with squamous cell or adenocarcinoma of the esophagus that meet these criteria might be suitable for the trial.

As an unphased trial, this study provides patients the opportunity to contribute to groundbreaking research that could lead to more effective and less toxic treatments for esophageal cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that proton radiation is safe for esophageal cancer?

Research has shown that proton radiation therapy is generally safe for treating esophageal cancer. Studies suggest it might be safer and more effective than traditional radiation, particularly in minimizing side effects on the heart and lungs. Proton therapy precisely targets cancer cells while sparing healthy tissue, potentially leading to fewer side effects.

Reports indicate that proton therapy, when combined with chemotherapy, is well-tolerated. It can help protect vital organs and reduce the risk of serious side effects. The overall safety appears promising, based on available evidence, making it a viable option for patients considering clinical trials for esophageal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Proton radiation is unique because it uses a targeted approach to treat esophageal cancer, potentially offering fewer side effects compared to traditional radiation therapies like X-rays. Unlike conventional radiation that can affect surrounding healthy tissues, proton radiation delivers high doses directly to the tumor with precision, sparing more of the surrounding healthy tissue. Researchers are excited about this treatment because it could reduce the overall damage to the body, leading to better quality of life for patients and potentially improving outcomes.

What evidence suggests that proton radiation might be an effective treatment for esophageal cancer?

Research shows that proton radiation therapy, which participants in this trial will receive, is a promising treatment for esophageal cancer. Studies have found that patients receiving proton therapy tend to live longer, with higher survival rates at three and five years compared to those receiving traditional photon therapy. Proton therapy may also be safer, causing less harm to the heart and lungs. One study found that proton therapy improved survival rates at two years more than other treatments like IMRT, another type of radiation therapy. Overall, proton therapy appears both effective and safe for treating esophageal cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Gary Yang, MD

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

This trial is for adults with confirmed primary squamous cell or adenocarcinoma of the esophagus, involving mid to lower regions or junction. They must have adequate organ function, no prior treatments for esophageal cancer, and be fit for surgery post-therapy. Pregnant women and those unable to use contraception are excluded.

Inclusion Criteria

I have had an endoscopy with a tissue sample taken.

My liver is working well.

Endoscopic ultrasound

Exclusion Criteria

My cancer is either very small and not spread to lymph nodes or very large.

Severe, active co-morbidity impacting survival

I cannot undergo surgery to remove my esophagus due to health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive a regimen of carboplatin and paclitaxel, which includes proton radiation therapy

6-8 weeks

Surgery

Definitive surgery is performed following chemotherapy and radiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Proton Radiation

Trial Overview The study tests a treatment combining carboplatin/paclitaxel chemotherapy with proton radiation therapy followed by surgery. It aims to improve outcomes over traditional chemo regimens by reducing toxicity and using proton beam technology for better dose distribution in localized esophageal cancer.

How Is the Trial Designed?

Group I: Proton radiation Experimental Treatment 1 Intervention

Proton radiation

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

Approved in United States as Proton Therapy for:

• Brain tumors
• Breast cancer
• Esophageal cancer
• Eye cancer
• Gynecological cancers
• Head and neck cancer
• Liver cancer
• Lung cancer
• Lymphoma
• Pancreatic cancer
• Prostate cancer
• Rectal cancer
• Sarcomas
• Spinal cord tumors

Approved in European Union as Proton Therapy for:

• Similar indications as in the United States, with specific approvals varying by country

Approved in Canada as Proton Therapy for:

• Similar indications as in the United States, with specific approvals varying by province

Approved in Japan as Proton Therapy for:

• Similar indications as in the United States, with specific approvals varying by region

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Published Research Related to This Trial

Proton beam therapy (PBT) may reduce radiation exposure to healthy tissues compared to traditional photon-based radiotherapy for early-stage esophageal cancer, potentially lowering the risk of cardiac and pulmonary complications.

Despite promising dosimetric studies suggesting advantages of PBT, there is still limited clinical data on its effectiveness in large populations and its impact on patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Esophageal Cancer. Solidum, JGN., Rojo, RD., Wo, JY., et al.[2022]

In a study of 44 patients with clinical T1 esophageal squamous cell carcinoma (ESCC) treated with concurrent chemo-proton therapy (CCPT), 98% achieved a complete response, indicating high efficacy of this treatment approach.

The 3-year overall survival rate was 95.2%, and even among the 11% who experienced local recurrence, all were successfully treated and remained recurrence-free after a median follow-up of 23 months, highlighting the safety and effectiveness of salvage endoscopic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic results of proton beam therapy with concurrent chemotherapy for cT1 esophageal cancer and salvage endoscopic therapy for local recurrence. Sato, D., Motegi, A., Kadota, T., et al.[2021]

Proton beam therapy (PBT) combined with concurrent chemotherapy (CChT) shows promising results in treating esophageal cancer, with a pathologic complete response rate of 28% in surgical patients and a near complete response rate of 50%.

While the treatment is associated with some acute toxicities, such as esophagitis and fatigue, the overall clinical outcomes are encouraging, suggesting that PBT/CChT may be a viable option for managing thoracic malignancies, warranting further comparison with traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy and concurrent chemotherapy for esophageal cancer. Lin, SH., Komaki, R., Liao, Z., et al.[2022]

In a study of 15 patients with esophageal carcinoma treated with proton beam irradiation (with or without x-ray), all primary tumor lesions disappeared, indicating high efficacy of this treatment approach.

Despite some patients developing esophageal ulcers post-treatment, these healed with conservative management, and the treatment showed promising long-term survival, with four patients living over five years and no local recurrences in superficial carcinoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for patients with esophageal carcinoma. Koyama, S., Tsujii, H., Yokota, H., et al.[2018]

Proton-beam therapy for locoregionally advanced esophageal cancer showed a high response rate, with 92% of patients (40 out of 51) achieving either a complete or partial response within 4 months of treatment.

The treatment was well-tolerated, with no interruptions due to radiation-induced side effects, and the overall 5-year survival rate was 21.1%, indicating that proton-beam therapy is a promising option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer. Mizumoto, M., Sugahara, S., Nakayama, H., et al.[2021]

Proton beam therapy shows promise as an effective treatment for locally confined esophageal cancer, with a 5-year overall survival rate of 34% among 46 patients studied, and a notably higher survival rate of 55% for those with early-stage T1 disease.

The therapy resulted in a 5-year disease-specific survival rate of 67%, indicating that proton therapy can effectively target cancer while potentially minimizing damage to surrounding healthy tissue, although further research is needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results of proton beam therapy for cancer of the esophagus. Sugahara, S., Tokuuye, K., Okumura, T., et al.[2018]

In a study of 202 patients with esophageal cancer treated with proton beam therapy, the 3-year overall survival rate was 66.7% and the 5-year survival rate was 56.3%, indicating promising efficacy for this treatment.

Proton beam therapy demonstrated lower rates of severe toxicities, with only 1% of patients experiencing grade three pericardial effusion and 0.5% experiencing grade three pneumonia, suggesting it may be a safer alternative to traditional photon radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Results of Proton Beam Therapy for Esophageal Cancer: Multicenter Retrospective Study in Japan. Ono, T., Wada, H., Ishikawa, H., et al.[2020]

Proton beam radiation therapy (PT) offers significant advantages over traditional photon radiation therapy for esophageal cancer, including reduced toxicity to healthy tissues and improved safety for tumors located near critical organs, as supported by recent multicenter studies.

A randomized phase II study confirmed that PT resulted in significantly lower toxicities compared to IMRT, and ongoing phase III trials are investigating whether PT could become the standard treatment for locally advanced and resectable esophageal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of proton therapy in esophageal cancer]. Créhange, G., Goudjil, F., Krhili, SL., et al.[2022]

Proton beam therapy (PBT) significantly reduced radiation exposure to the lungs and heart compared to photon-based radiotherapy in a study of 31 patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Despite the dosimetric advantages of PBT, there were no significant differences in short-term postoperative outcomes or overall and disease-free survival rates between the PBT and photon groups after a median follow-up of 17 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute. Choi, JH., Lee, JM., Kim, MS., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9407004/

Proton Beam Therapy for Esophageal Cancer - PMC Furthermore, three- and five-year OS rates of 66.7% and 56.3% were reported [48]. These results are higher than the previous studies on photon ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2808359

Efficacy and Safety in Proton Therapy and Photon ... Meaning These findings suggest that proton therapy may be more effective and safer than photon therapy for patients with esophageal cancer.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2331518023002366

Proton Therapy With Concurrent Chemotherapy for ... Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity.

4. mdpi.com mdpi.com/2072-6694/15/23/5524

Treatment Outcomes of Proton Beam Therapy for ... This research found that PBT showed promising results in terms of favorable overall survival rates and reducing toxicities in ESCC patients.

5. jto.org jto.org/article/S1556-0864(23)02430-9/fulltext

Comparative Effectiveness of Intensity-Modulated Proton ... Specifically, at the two-year mark, ESCC-specific survival rates for patients undergoing IMPT and IMRT stood at 62.03% and 51.77%, respectively.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10427943/

Efficacy and Safety in Proton Therapy and Photon Therapy for ... These findings suggest that proton therapy may be more effective and safer than photon therapy for patients with esophageal cancer.

7. advancesradonc.org advancesradonc.org/article/S2452-1094(24)00110-6/fulltext

A Prospective Pilot Study of Pencil Beam Scanning Proton ... Five-year outcome estimates were overall survival at 46%, progression-free survival at 39%, local-regional recurrence at 17%, and distant ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03482791

Proton Beam Therapy in the Treatment of Esophageal ... The investigators have a prospective experience of physician-reported toxicity and patient outcome using IMRT for patients with inoperable esophagus cancer that ...