Proton Therapy vs Photon Radiation for Esophageal Cancer

Recruiting at 88 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must be taking: FOLFOX

Disqualifiers: Metastatic disease, Active malignancy, 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: 28

Duration: 5.5 weeks

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well proton beam radiation therapy compared with intensity modulated photon radiotherapy works in treating patients with stage I-IVA esophageal cancer. Proton beam radiation therapy uses a beam of protons (rather than x-rays) to send radiation inside the body to the tumor without damaging much of the healthy tissue around it. Intensity modulated photon radiotherapy uses high-energy x-rays to deliver radiation directly to the tumor without damaging much of the healthy tissue around it. It is not yet known whether proton beam therapy or intensity modulated photon radiotherapy will work better in treating patients with 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 data supports the effectiveness of this treatment for esophageal cancer?

Research shows that proton therapy, particularly intensity-modulated proton therapy (IMPT), is better at protecting the heart and lungs compared to photon radiation therapy. This means it can target the cancer more precisely while reducing harm to nearby healthy tissues. ^{1 2 3 4 5}

Is proton therapy safe for treating esophageal cancer?

Proton therapy and photon radiation therapy are both used to treat esophageal cancer, and studies suggest that proton therapy may reduce exposure to healthy tissues like the heart and lungs, potentially leading to fewer side effects. However, factors like respiratory motion can affect treatment accuracy, so careful planning is needed to ensure safety. ^{2 3 5 6 7}

How is the treatment Proton Therapy vs Photon Radiation for Esophageal Cancer different from other treatments?

Proton therapy is unique because it can precisely target tumors while minimizing damage to nearby healthy tissues, like the heart and lungs, which is particularly beneficial for esophageal cancer. This precision reduces side effects and allows for potentially higher doses to the tumor, improving treatment outcomes compared to traditional photon radiation therapy. ^{2 3 5 7 8}

Research Team

Steven Lin

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with stage I-IVA esophageal cancer, either adenocarcinoma or squamous cell carcinoma. They should not have metastatic disease, prior thoracic radiotherapy overlapping the treatment area, uncontrolled infections or heart conditions, and must not be pregnant. Eligible participants need a certain blood count level and organ function within normal ranges.

Inclusion Criteria

I will consult a surgeon to see if I can have surgery after chemoradiation.

I had a scan after my initial chemotherapy.

Stage I-IVA, excluding T4b, according to the American Joint Committee on Cancer (AJCC) 8th edition based on the following diagnostic workup: History/physical examination; Whole-body fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) with or without (+/-) contrast (preferred) or chest/abdominal (include pelvic if clinically indicated) CT with contrast; For patients who DID NOT receive induction chemotherapy, scan must occur within 30 days prior to Step 1 registration; For patients who DID receive induction chemotherapy, scan must occur: Within 30 days after final induction chemotherapy dose; OR Within 30 days prior to Step 1 registration; Note: Patients who had prior endoscopic mucosal resection (EMR) with a diagnosis of AJCC stage I-IVA, excluding T4b, esophageal cancer are eligible; Surgical consultation to determine whether or not the patient is a candidate for resection after completion of chemoradiation; Induction chemotherapy for the current malignancy prior to concurrent chemoradiation allowed if last dose is no more than 90 days and no less than 10 days prior to Step 1 registration. Only FOLFOX will be allowed as the induction chemotherapy regimen; Zubrod performance status 0, 1, or 2; Absolute neutrophil count (ANC) (within 30 days prior to Step 1 registration); For patients who DID NOT receive induction chemotherapy: ANC >= 1,500 cells/mm^3; For patients who DID receive induction chemotherapy: ANC >= 1,000 cells/mm^3; Platelets (within 30 days prior to Step 1 registration); For patients who DID NOT receive induction chemotherapy: Platelets >= 100,000/uL; For patients who DID receive induction chemotherapy: Platelets >= 75,000/uL; Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable) (within 30 days prior to Step 1 registration); Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or Creatinine clearance > 40 mL/min estimated by Cockcroft-Gault formula (within 30 days prior to Step 1 registration); Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 30 days prior to Step 1 registration); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 30 days prior to Step 1 registration); Negative pregnancy test (serum or urine) within 14 days prior to Step 1 registration for women of child bearing potential; The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria

Pregnant and/or nursing females

My esophageal cancer is located 15-18 cm from my teeth.

I do not have an active infection needing IV antibiotics.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo either PBT or IMRT over 28 fractions, 5 days a week for 5.5 weeks, with concurrent chemotherapy

5.5 weeks

28 visits (in-person)

Surgery

Patients may undergo an esophagectomy within 4-8 weeks after completion of chemotherapy and radiation therapy

4-8 weeks post-treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years with follow-ups every 3-6 months, then annually

Treatment Details

Interventions

• Intensity-Modulated Radiation Therapy
• Proton Beam Radiation Therapy

Trial Overview The study compares proton beam radiation therapy to intensity-modulated photon radiotherapy in treating esophageal cancer. Proton therapy uses protons to target the tumor with minimal damage to surrounding tissue; photon therapy uses high-energy x-rays similarly focused.

Participant Groups

Group I: Group I (PBT, Chemotherapy, Esophagectomy) Experimental Treatment 10 Interventions

Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing PBT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.

Group II: Group II (IMRT, Chemotherapy, Esophagectomy) Active Control 10 Interventions

Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks to a total dose of 50.4 Gy. Patients also receive chemotherapy (Choice of 3 regimens: 1. Carboplatin/Paclitaxel, 2. FOLFOX/CAPOX or 3. Docetaxel/5-FU \[with capecitabine as an acceptable substitute for 5-FU\]) per institutional standards while undergoing IMRT. Within 4-8 weeks after completion of chemotherapy and radiation therapy, patients may undergo an esophagectomy per physician discretion.

Intensity-Modulated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in European Union as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

Approved in Canada as IMRT for:

• Oropharyngeal cancer
• Head and neck cancers
• Prostate cancer
• Breast cancer
• Lung cancer

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+

Findings from Research

In a study of 343 esophageal cancer patients treated with definitive chemoradiotherapy, proton beam therapy (PBT) showed significantly better overall survival and progression-free survival compared to intensity-modulated radiation therapy (IMRT).

PBT was particularly beneficial for patients with stage III disease, demonstrating a 5-year overall survival rate of 34.6% compared to 25.0% for IMRT, while no significant differences were found for patients with earlier stages of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Outcomes After Definitive Chemoradiotherapy Using Proton Beam Therapy Versus Intensity Modulated Radiation Therapy for Esophageal Cancer: A Retrospective, Single-Institutional Analysis. Xi, M., Xu, C., Liao, Z., et al.[2018]

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]

Proton therapy using posterior beam angles (2PAPTVRO) showed greater robustness against anatomical changes and respiratory motion in esophageal cancer treatment compared to intensity-modulated radiation therapy (IMRT), with only 1 out of 26 patients experiencing inadequate coverage.

Interplay effects from respiratory motion significantly impacted dose distribution when delivering a single fraction, but these effects were mitigated after 10 fractions, indicating that multiple treatment sessions can improve overall treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for Motion Robust Proton Therapy With Pencil Beam Scanning for Esophageal Cancer. Møller, DS., Poulsen, PR., Hagner, A., et al.[2021]

Intensity-modulated proton therapy (IMPT) combined with chemotherapy showed a high clinical complete response rate of 84% in 19 patients with esophageal carcinoma, indicating its efficacy in treating this type of cancer.

With a median follow-up of 17 months, patients experienced a median overall survival of 39.2 months, and the treatment was associated with acceptable levels of acute toxicity, primarily esophagitis and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. Prayongrat, A., Xu, C., Li, H., et al.[2022]

Intensity-modulated proton therapy (IMPT) significantly reduces radiation exposure to organs at risk (OARs) such as the lungs and heart compared to intensity-modulated x-ray therapy (IMXT) in treating esophageal squamous cell carcinoma (ESCC), based on a study involving 25 patients.

Different IMPT beam configurations can optimize OAR sparing depending on tumor location, with specific configurations achieving the lowest doses to the lungs, heart, and liver while maintaining effective target coverage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intensity modulated proton therapy beam configurations for treating thoracic esophageal cancer. Oonsiri, S., Kitpanit, S., Kannarunimit, D., et al.[2022]

In a randomized trial involving 145 patients with locally advanced esophageal cancer, proton beam therapy (PBT) significantly reduced the total toxicity burden (TTB) compared to intensity-modulated radiation therapy (IMRT), with TTB being 2.3 times higher for IMRT.

Despite the reduced toxicity with PBT, the progression-free survival (PFS) and overall survival rates were similar between the two treatment modalities, indicating that PBT offers a safer option without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer. Lin, SH., Hobbs, BP., Verma, V., et al.[2021]

Intensity-modulated proton therapy (IMPT) significantly reduces radiation exposure to the lungs, heart, and liver compared to intensity-modulated photon radiotherapy (IMRT) in patients with unresectable distal esophageal cancer, as shown in a study involving 10 patients.

The optimal beam arrangement for IMPT (AP/LPO/RPO) effectively spares critical organs while allowing for potential dose escalation to the tumor, suggesting a promising approach for improving treatment safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study. Welsh, J., Gomez, D., Palmer, MB., et al.[2023]

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]

References

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

Comparative Outcomes After Definitive Chemoradiotherapy Using Proton Beam Therapy Versus Intensity Modulated Radiation Therapy for Esophageal Cancer: A Retrospective, Single-Institutional Analysis. [2018]

2. United States 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. [2022]

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

Strategies for Motion Robust Proton Therapy With Pencil Beam Scanning for Esophageal Cancer. [2021]

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

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of intensity modulated proton therapy beam configurations for treating thoracic esophageal cancer. [2022]

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

Randomized Phase IIB Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for Locally Advanced Esophageal Cancer. [2021]

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

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study. [2023]

8. France pubmed.ncbi.nlm.nih.gov

[The role of proton therapy in esophageal cancer]. [2022]