A Phase 3 interventional study of Photon Radiotherapy and Proton Radiotherapy in Esophageal Cancer, Radiotherapy and Side Effect, sponsored by University of Aarhus. Recruiting at 15 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-12-17.
Sponsored by University of Aarhus · Phase 3, Interventional, and Treatment
The PROTECT trial will test the hypothesis that proton (PT) -enabled radiation dose reductions to sensitive, normal tissues will result in lower rates of treatment-related pulmonary complications in esophageal cancer compared to standard photon therapy (XT).
PROTECT is a unblinded international multicenter randomized phase III study for patients with operable EC or EGC receiving nCXT (standard of care) or nCPT (intervention). The study will be open-label for the patient and the treating physician.
The radiation dose is either 41.4 Gy in 23 fractions, five fractions per week or 50.4 Gy in 28 fractions, five fractions per week. Prior to trial opening, each proton center will determine a single dose regimen for all patients treated in that specific proton center and its assigned photon centers.
The protocol prescribes that all referring centers will use the same chemotherapy regimen, which is weekly carboplatin (AUC 2), and paclitaxel (50 mg/m2), five cycles, irrespective of choice of dose regimen. Chemotherapy is a non-investigational drug.
Prior to referral to any proton therapy center, patients will be randomed (1:1) to either nCXT or nCPT. Only patients randomized to the PT arm will be referred to a PT center. Randomization will be performed centrally using an online 24-hour web-based system maintained by the Clinical Trial Office at Aarhus University Hospital, ensuring allocation concealment to the clinical investigators. The method of randomization will be stratified permuted blocks of size 4 and 6 (selected randomly) with the following strata:
1,593 studies on the registry are indexed under Esophageal Neoplasms; 461 are open to participants now.
This study's planned enrollment of 396 is above the median of 58 across 1,171 interventional studies indexed under Esophageal Neoplasms.
Browse Esophageal Neoplasms studies →University of Aarhus is the lead sponsor of 1,274 studies on the registry; 183 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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).
Exclusion Criteria:
Patients who meet one or more of the following exclusion criteria cannot be included in the study:
Standard arm with neoadjuvant chemoradiotherapy (nCXT) with photons
Radiation: Photon Radiotherapy
Experimental arm with neoadjuvant chemoradiotherapy (nCPT) with protons
Radiation: Proton Radiotherapy
nCXT consists of weekly carboplatin and paclitaxel for 5 weeks, following the CROSS trial. The radiation dose will be either 41.4 Gy in 23 fractions or 50.4 Gy in 28 fractions
nCPT consists of weekly carboplatin and paclitaxel for 5 weeks, following the CROSS trial. The radiation dose will be either 41.4 Gy in 23 fractions or 50.4 Gy in 28 fractions
Also known as: Proton Therapy
Pulmonary complications
Incidence of pulmonary complications during and following nCPT or nCXT and surgery
Time frame: from randomization until 90 days after surgery
Early toxicity
Predefined items ≥ grade 2 scored by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: from start of nCPT or nCXT until surgery
Late toxicity
Predefined items ≥ grade 2 scored by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: up to 5 years
Postoperative complications
Predefined items scored by Clavien-Dindo and Comprehensive Complications Index (CCI)
Time frame: from surgery until 90 days after surgery
Major cardiovascular events (MACE)
Predefined cardiovascular events scored by MACE
Time frame: up to 5 years
Patient-reported outcome measures
EORTC quality of life questionnaire
Time frame: up to 5 years
Compliance with trimodality treatment
The proportion of patients complying with trimodality treatment in each arm
Time frame: 3 months
Pathological response
tumor regression grade for the primary tumor scored according to Mandard score.
Time frame: immediately after surgery
Cumulative incidence of loco-regional failure
Locoregional failure evaluated according to RECIST with all failures within the irradiated volume counting as events.
Time frame: from date of randomization up to 5 years
Pattern of failure
First site of failure will be divided in loco-regional lymph node failures, loco-regional failures in anastomosis, and distant extra-cranial and intra-cranial failures. All loco-regional failures will be divided in failures inside and outside the treatment volume, which is defined to be within the specified treatment dose.
Time frame: up to 5 years
Disease-free survival (DFS)
Disease control evaluated according to RECIST with any recurrence (locoregional or distant) as well as death from any cause, whatever occurs first, will be considered as events.
Time frame: up to 5 years
Overall survival (OS)
Death from all causes will considered as events
Time frame: up to 5 years
Total toxicity burden (TTB)
The combined toxicity scale TTB used in the trial by Lin et al (Lin 2020)
Time frame: from randomization until 90 days after surgery
Concordance of observed pulmonary complications with predicted complications from NTCP models
Comparison of observed and predicted toxicity rates
Time frame: up to 5 years
Blood biomarkers as predictors for treatment failure
circulating tumor DNA
Time frame: up to 5 years
Proportion of patients receiving adjuvant immunotherapy
The actual number of patients starting adjuvant immunotherapy will be recorded
Time frame: up to 5 years
Cost-effectiveness of proton therapy relative to photon therapy
Incremental cost effectiveness ratios (ICERs), cost per QALY gained, cost per complication avoided, and cost per total toxicity burden avoided will be reported.
Time frame: up to 5 years
FDG/PET CT as predictors for treatment failure
Correlation between diagnostic PET, planning PET-CT and PET at 12 months
Time frame: 12 months
Concordance of observed cardiac complications with predicted
Comparison of observed and predicted toxicity rates
Time frame: Up to 5 years
Plan to share: No
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