Proton Beam Therapy for Esophageal Cancer

Overseen By Shahed Badiyan, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Other cancers, Heart failure, Angina, 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

22 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators plan to include both operable and inoperable patients with esophagus cancer in this prospective trial. Since both proton and photon treatments are biologically equivalent, the investigators do not expect a difference in tumor control compared to intensity modulated radiation therapy (IMRT). The investigators have a prospective experience of physician-reported toxicity and patient outcome using IMRT for patients with inoperable esophagus cancer that will serve as a comparison group. For the resectable patients receiving trimodality therapy (chemoradiation followed by surgery), the investigators will carefully track toxicity and patient outcomes prospectively. The central hypothesis is that the biologic efficacy for tumor control should be similar between protons and photons, and therefore survival measures should be similar between the two groups, but that the main difference lies in the total severe toxicities experienced by the patients undergoing therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since induction chemotherapy is allowed, it might be possible to continue some treatments. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the treatment Proton Beam Therapy for esophageal cancer?

Proton Beam Therapy (PBT) is promising for esophageal cancer as it reduces radiation exposure to nearby organs, potentially improving outcomes compared to traditional methods. Studies suggest PBT, especially when combined with chemotherapy, may offer better results and fewer side effects than photon-based radiotherapy. ^{1 2 3 4 5}

Is proton beam therapy generally safe for humans?

Proton beam therapy (PBT) is considered to be generally safe and may reduce radiation exposure to nearby organs like the heart and lungs compared to traditional radiation methods, potentially leading to fewer side effects. ^{1 2 3 5 6}

How is Proton Beam Therapy different from other treatments for esophageal cancer?

Proton Beam Therapy (PBT) is unique because it targets cancer cells more precisely, reducing radiation exposure to nearby healthy organs like the heart and lungs, which can lower the risk of side effects compared to traditional radiation treatments. ^{1 2 3 4 5}

Research Team

Gregory Vlacich, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with stage II or III esophageal cancer who can consent in English and have financial coverage for proton therapy. They must not be pregnant, agree to use contraception, and have normal organ function. Excluded are those with recent heart attacks, uncontrolled illnesses, or other cancers within the past 3 years.

Inclusion Criteria

AST(SGOT)/ALT(SGPT) < 3.0 x IULN

Platelets > 75,000/mcl

Total bilirubin < 1.5 x institutional upper limit of normal (IULN)

Exclusion Criteria

Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 7 days of the start of treatment.

I am scheduled for radiation without chemo or chemo alone.

I do not have any severe illnesses that could interfere with the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants receive proton beam therapy and standard of care chemotherapy

8-10 weeks

Surgery

Surgery is performed for resectable patients following chemoradiation

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Proton Beam Therapy

Trial Overview The study compares the effectiveness of Proton Beam Therapy against Intensity Modulated Radiation Therapy (IMRT) in treating esophageal cancer. It aims to see if there's a difference in severe toxicities between these treatments while tracking tumor control and patient survival.

Participant Groups

Group I: Arm 2: Unresectable (proton beam therapy) Experimental Treatment 2 Interventions

* Proton beam therapy: total dose of 59.4 or 60 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Patient-reported outcome measures (PROs) performed at several time points

Group II: Arm 1: Resectable (proton beam therapy) Experimental Treatment 2 Interventions

* Proton beam therapy: total dose of 50 or 50.4 Gy * Standard of care chemotherapy - the clinical trial doesn't dictate anything about the chemotherapy given, it is the treating physician's decision * Surgery should ideally be performed no later than 8 to 10 weeks after completing chemoradiation * Patient-reported outcome measures (PROs) performed at several time points

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

Approved in United States as Proton Beam Therapy for:

• Various cancers including prostate, breast, lung, liver, and head and neck cancers

Approved in European Union as Proton Therapy for:

• Various cancers including ocular melanoma, chordomas, chondrosarcomas, and certain pediatric cancers

Approved in Japan as Proton Beam Therapy for:

• Various cancers including prostate, liver, and ocular melanoma

Approved in Canada as Proton Therapy for:

• Various cancers including ocular melanoma and certain pediatric cancers

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

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 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) 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]

References

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

Proton beam therapy and concurrent chemotherapy for esophageal cancer. [2022]

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

Hyperfractionated concomitant boost proton beam therapy for esophageal carcinoma. [2019]

3. Japan 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. [2021]

4. Switzerland 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. [2022]

5. China pubmed.ncbi.nlm.nih.gov

The emerging role of proton therapy for esophagus cancer. [2023]

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

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma. [2018]