PROton Versus Photon Therapy for Esophageal Cancer

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

396 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-01

Study Completion Date

2032-12-01

Brief Summary

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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).

Detailed Description

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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:

* Histopathology (non-squamous vs squamous cell carcinoma)
* Planned surgical technique (open versus minimal invasive/robotic or hybrid)
* Proton center and sites assigned to this center (which will deliver the nCXT)

Conditions

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Esophageal Cancer Radiotherapy Side Effect Proton Therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Photon Arm

Standard arm with neoadjuvant chemoradiotherapy (nCXT) with photons

Group Type ACTIVE_COMPARATOR

Photon Radiotherapy

Intervention Type 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

Proton Arm

Experimental arm with neoadjuvant chemoradiotherapy (nCPT) with protons

Group Type EXPERIMENTAL

Proton Radiotherapy

Intervention Type 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

Interventions

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Photon 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

Intervention Type RADIATION

Proton Radiotherapy

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

Intervention Type RADIATION

Other Intervention Names

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Proton Therapy

Eligibility Criteria

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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

* 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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marianne Nordsmark, Dr.

Role: STUDY_DIRECTOR

University of Aarhus

Karin Haustermans, Dr.

Role: STUDY_CHAIR

UKleuven

Identifier Type: -

Identifier Source: org_study_id

PROton Versus Photon Therapy for Esophageal Cancer - a Trimodality Strategy

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Study Design

Study Groups

Photon Arm

Photon Radiotherapy

Proton Arm

Proton Radiotherapy

Interventions

Photon Radiotherapy

Proton Radiotherapy

Other Intervention Names

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

University of Leeds

KU Leuven

University College, London

Aarhus University Hospital

Technische Universität Dresden

Academisch Ziekenhuis Groningen

CNAO National Center of Oncological Hadrontherapy

Agenzia Nazionale per i Servizi Sanitari Regionali

Centre Antoine Lacassagne

Centre Leon Berard

Institut Curie

Maastro Clinic, The Netherlands

University College London Hospitals

The Christie NHS Foundation Trust

Paul Scherrer Institut, Center for Proton Therapy

HollandPTC

IBA worldwide

Varian- A Siemens Healthineer Company

University of Aarhus

Responsible Party

Principal Investigators

Marianne Nordsmark, Dr.

Karin Haustermans, Dr.

Locations

Catholic University of Leuven

Aarhus University Hospital (AUH)

Centre Léon Bérard (CLB)

Centre Antoine Lacassagne (CAL)

Institut Curie

Technische Universität Dresden (TUD)

San Raffaele Hospital

Centro Nazionale di Adroterapia Oncologica (CNAO)

Azienda Provinciale Per I Servizi Sanitari (APSS)

Academisch Ziekenhuis Groningen (UMCG)

Stichting Maastricht Radiation Oncology (MAASTRO)

Paul Scherrer Institute (PSI)

University Hospital Zurich (USZ)

University College London Hospital (UCLH)

The Christie NHS foundation trust

Countries

Central Contacts

Dorte Winter

Toke Hansen, PhD

Facility Contacts

Pieter Populaire

Karin Haustermans

Dorte Winther, Dr.

Marianne Nordsmark

Hanna Mortensen

Laurie Bissuel

Jessica Serrand

Jérôme Doyen

Gilles Crehange

Esther Troost

Elena Mazza

Nadia Di Muzio

Cristina Bono

Ester Orlandi

Daniele Scartoni

Ulrike Kliebsch