Proton Therapy vs Photon Radiation for Esophageal Cancer

Recruiting at 95 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two types of radiation treatments to determine which is more effective for esophageal cancer, a cancer affecting the tube connecting the throat to the stomach. The treatments being tested are proton beam radiation (proton therapy), which uses protons to target the tumor, and photon radiation, which uses high-energy x-rays. Researchers aim to identify which method treats the cancer more effectively while sparing healthy tissue. The trial seeks participants with stage I-IVA esophageal cancer who are considering surgery after radiation and chemotherapy. Participants should have a history of esophageal or gastroesophageal junction cancer diagnosed by a doctor. 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.

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.

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

Research has shown that proton beam radiation therapy is generally safe for treating esophageal cancer. Studies suggest it may cause fewer side effects, particularly affecting the heart and lungs, compared to other treatments. Patients often report fewer issues with these organs when receiving proton therapy.

Intensity-modulated photon radiotherapy is also considered safe. It uses precise, high-energy x-rays to target the tumor while protecting healthy tissue. Both treatments aim to minimize harm to healthy parts of the body, but proton therapy might slightly reduce side effects more effectively.

Overall, both treatments are well-tolerated by patients, and ongoing research continues to support their safety in treating esophageal cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the potential of Proton Beam Radiation Therapy (PBT) for esophageal cancer because it targets tumors with precision, potentially reducing damage to surrounding healthy tissues compared to the conventional Intensity-Modulated Radiation Therapy (IMRT). This precision could lead to fewer side effects and improved quality of life for patients undergoing treatment. With both PBT and IMRT being paired with chemotherapy and the option of surgery, this trial hopes to determine which combination provides the most effective and safest outcomes for patients battling esophageal cancer.

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

This trial will compare Proton Beam Radiation Therapy (PBT) with Intensity-Modulated Radiation Therapy (IMRT) for treating esophageal cancer. Research has shown that PBT might be more effective and safer than traditional photon therapy. One study found that 62.03% of patients who received PBT were alive after two years, compared to 51.77% of those who had photon therapy. PBT is also linked to fewer side effects, particularly causing less harm to the heart and lungs. This suggests that PBT could be a promising option for people with esophageal cancer, offering a better chance of survival with fewer complications. Participants in this trial will receive either PBT or IMRT, along with chemotherapy and potentially an esophagectomy. ^{1 2 4 5 6}

Who Is on the Research Team?

Steven H Lin

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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.

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

I had a scan after my initial chemotherapy.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Group I (PBT, concurrent chemotherapy, esophagectomy) Experimental Treatment 14 Interventions

Patients undergo PBT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive chemotherapy consisting of carboplatin/paclitaxel, or FOLFOX/CAPOX, or docetaxel/5-FU (with capecitabine an acceptable substitute for 5-FU) as determined by the patient and their treating physician while undergoing PBT. Additionally, patients undergo blood sample collection, and PET/CT or CT throughout the study.

Group II: Group II (IMRT, concurrent chemotherapy, esophagectomy) Active Control 14 Interventions

Patients undergo IMRT over 28 fractions 5 days a week for 5.5 weeks. Patients also receive chemotherapy consisting of carboplatin/paclitaxel, or FOLFOX/CAPOX, or docetaxel/5-FU (with capecitabine an acceptable substitute for 5-FU) as determined by the patient and their treating physician while undergoing IMRT. Additionally, patients undergo blood sample collection, and PET/CT or CT throughout the study.

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

Citations

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

Proton Beam Therapy for Esophageal Cancer - PMC In this review, we present the role of PBT for esophageal cancer, including treatment planning, early clinical comparisons with photon-based techniques, ...

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. 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 ...