PROton Versus Photon Therapy for Esophageal Cancer - a Trimodality Strategy

NCT05055648 | Recruiting Phase 3 DMC

• 1 other identifier: DCPT101008134
• Study Type: interventional
• Target: 396
• Locations: 8 countries
• Sites: 15

Brief Summary

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).

Conditions

Esophageal Cancer; Radiotherapy; Side Effect; Proton Therapy

Outcome Measures

Primary Outcomes (1)

• Pulmonary complications

  Incidence of pulmonary complications during and following nCPT or nCXT and surgery

  from randomization until 90 days after surgery

Secondary Outcomes (11)

• Early toxicity

  from start of nCPT or nCXT until surgery

• Late toxicity

  up to 5 years

• Postoperative complications

  from surgery until 90 days after surgery

• Major cardiovascular events (MACE)

  up to 5 years

• Patient-reported outcome measures

  up to 5 years

Other Outcomes (7)

• Total toxicity burden (TTB)

  from randomization until 90 days after surgery

• Concordance of observed pulmonary complications with predicted complications from NTCP models

  up to 5 years

• Blood biomarkers as predictors for treatment failure

  up to 5 years

Study Arms (2)

Photon Arm

ACTIVE COMPARATOR

Standard arm with neoadjuvant chemoradiotherapy (nCXT) with photons

Radiation: Photon Radiotherapy

Proton Arm

EXPERIMENTAL

Experimental arm with neoadjuvant chemoradiotherapy (nCPT) with protons

Radiation: Proton Radiotherapy

Interventions

Photon Radiotherapy RADIATION

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

Photon Arm

Proton Radiotherapy RADIATION

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

Proton Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Aarhus: lead
• University of Leeds: collaborator
• KU Leuven: collaborator
• University College, London: collaborator
• Aarhus University Hospital: collaborator
• Technische Universität Dresden: collaborator
• Academisch Ziekenhuis Groningen: collaborator
• CNAO National Center of Oncological Hadrontherapy: collaborator
• Agenzia Nazionale per i Servizi Sanitari Regionali: collaborator
• Centre Antoine Lacassagne: collaborator
• Centre Leon Berard: collaborator
• Institut Curie: collaborator
• Maastro Clinic, The Netherlands: collaborator
• University College London Hospitals: collaborator
• The Christie NHS Foundation Trust: collaborator
• Paul Scherrer Institut, Center for Proton Therapy: collaborator
• HollandPTC: collaborator
• IBA worldwide: collaborator
• Varian- A Siemens Healthineer Company: collaborator

Study Sites (15)

Catholic University of Leuven

Leuven, Belgium

RECRUITING

Aarhus University Hospital (AUH)

Aarhus, 8000, 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, 8091, Switzerland

RECRUITING

University College London Hospital (UCLH)

London, United Kingdom

WITHDRAWN

The Christie NHS foundation trust

Manchester, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Proton Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Study Officials

• Marianne Nordsmark, Dr.

  University of Aarhus

  STUDY DIRECTOR

• Karin Haustermans, Dr.

  UKleuven

  STUDY CHAIR

Central Study Contacts

Dorte Winter

CONTACT

+45 78456442; dorte.skriver.winther@auh.rm.dk

Toke Hansen, PhD

CONTACT

+45 78456442; tokeha@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label, non-blinded, international multicenter, randomized phase III study

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: September 24, 2021
• Study Start: May 1, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2032
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); DK (1); GB (2); IT (3); BE (1); CH (2); FR (3); DE (1)