Comparing proton and photon therapy for esophageal cancer treatment

PROton Versus Photon Therapy for Esophageal Cancer - a Trimodality Strategy (PROTECT) a Multicenter International Randomized Phase III Study of Neoadjuvant Proton Versus Photon Chemoradiotherapy in Locally Advanced Esophageal Cancer

This study is testing if proton therapy can help people with operable esophageal cancer have fewer lung problems after treatment compared to the usual photon therapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 396 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Aarhus (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 15 sites (Leuven and 14 other locations)
• Trial ID: NCT05055648 on ClinicalTrials.gov

What this trial studies

The PROTECT trial aims to evaluate whether proton therapy can reduce treatment-related pulmonary complications in patients with operable esophageal cancer compared to standard photon therapy. This international multicenter randomized phase III study will involve patients receiving either neoadjuvant chemotherapy followed by proton therapy or photon therapy. Patients will be randomly assigned to one of the two treatment arms, with the study ensuring allocation concealment through a centralized online randomization system. The trial will also standardize chemotherapy regimens across all participating centers to maintain consistency in treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically verified esophageal or gastro-esophageal junction cancer who are eligible for surgery.

Not a fit: Patients with advanced esophageal cancer or those who are not candidates for surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment outcomes and reduced side effects for patients with esophageal cancer.

How similar studies have performed: Other studies have shown promising results with proton therapy in various cancers, suggesting potential benefits in this novel approach for esophageal cancer.

Eligibility criteria

Inclusion Criteria:

* Patients with histologically verified squamous cell carcinoma or adenocarcinoma (including signet cell carcinoma and large cell carcinoma, not further specified) of the esophagus (E) or gastro-esophageal junction (GEJ).

  * FDG PET/CT performed.
  * Tumor stage according to TNM (8th edition): cT1-4a and/or cN+, cM0.
  * Age ≥18 years.
  * Performance status WHO ≤2.
  * Adequate laboratory findings: hematological: hemoglobin \> 90 g/L, absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 75 x 109/L hepatic: bilirubin ≤ 1.5 x upper limit of normal (ULN), ALAT ≤ 3 x ULN renal: creatinine ≤ 1.5 x ULN, GFR (may be calculated) \> 30 ml/min
  * MDT decision on suitability to undergo curatively intended nCXT or nCPT followed by surgery.
  * Planned transthoracic esophagectomy or gastrectomy being open, minimally invasive of combination of both.
  * Ability to adhere to procedures for study and follow-up.
  * Patients with low risk cancers with a life expectancy above 5 years (e.g. low risk prostate cancer) are allowed in the study. Adequately treated diagnoses such as cervix uteri carcinoma in situ, in situ urothelial carcinoma or localized non-melanoma skin cancer are allowed, regardless of time of diagnosis.
  * Patients of childbearing potential: pregnancy prevention according to the standards of each country. Patients of childbearing potential must present a negative pregnancy test. Patients and their partners must use effective contraception. Patients of childbearing potential included in the study must use oral contraceptives, intrauterine devices, depot injection of progestin subdermal implantation, a hormonal vaginal ring, or transdermal patch during the study treatment and one month after.

Exclusion Criteria:

Patients who meet one or more of the following exclusion criteria cannot be included in the study:

* Prior thoracic XT or PT, chemotherapy or surgical resection in the esophageal/gastric region (previous EMR or ESD is allowed).
* Tumor \< 3 cm from oropharyngeal sphincter.
* Planned transhiatal resection
* Patients with other previous malignancies are excluded unless a complete remission or complete resection was achieved at least 5 years prior to study entry.
* Any unstable systemic disease (including clinically significant lung and cardiovascular disease, unstable angina, New York Heart Association (NYHA) grade III-IV congestive heart, severe hepatic, renal or metabolic disease or active inflammatory bowel disease).
* Symptomatic peripheral neuropathy greater than grade 1 (scored according to CTCAE v5.0).
* Any other serious or uncontrolled illness, which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial.
* Unable to understand and digest study patient information or comply with study treatment and safety instructions.
* Gastro-esophageal stent within the irradiated volume.

Where this trial is running

Leuven and 14 other locations

• Catholic University of Leuven — Leuven, Belgium (Recruiting)
• Aarhus University Hospital (AUH) — Aarhus, Denmark (Recruiting)
• Centre Léon Bérard (CLB) — Lyon, France (Not_yet_recruiting)
• Centre Antoine Lacassagne (CAL) — Nice, France (Not_yet_recruiting)
• Institut Curie — Paris, France (Not_yet_recruiting)
• Technische Universität Dresden (TUD) — Dresden, Germany (Recruiting)
• San Raffaele Hospital — Milan, Italy (Recruiting)
• Centro Nazionale di Adroterapia Oncologica (CNAO) — Pavia, Italy (Recruiting)
• Azienda Provinciale Per I Servizi Sanitari (APSS) — Trento, Italy (Recruiting)
• Academisch Ziekenhuis Groningen (UMCG) — Groningen, Netherlands (Withdrawn)
• Stichting Maastricht Radiation Oncology (MAASTRO) — Maastricht, Netherlands (Withdrawn)
• Paul Scherrer Institute (PSI) — Villigen, Switzerland (Recruiting)
• University Hospital Zurich (USZ) — Zurich, Switzerland (Recruiting)
• University College London Hospital (UCLH) — London, United Kingdom (Withdrawn)
• The Christie NHS foundation trust — Manchester, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Dorte Winter

Conditions Esophageal Cancer; Radiotherapy; Side Effect; Proton Therapy