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JOURNAL ONKOLOGIE – STUDIE
PROTECT

PROton Versus Photon Therapy for Esophageal Cancer - a Trimodality Strategy

Rekrutierend

NCT-Nummer:
NCT05055648

Studienbeginn:
Mai 2022

Letztes Update:
02.11.2022

Wirkstoff:
-

Indikation (Clinical Trials):
Esophageal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
University of Aarhus

Collaborator:
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

Studienleiter

Marianne Nordsmark, Dr.
Study Director
University of Aarhus
Karin Haustermans, Dr.
Study Chair
UKleuven

Kontakt

Studienlocations
(3 von 13)

Aarhus University Hospital (AUH)
8000 Aarhus
DenmarkRekrutierend» Google-Maps
Ansprechpartner:
Marianne Nordsmark, Dr.
E-Mail: marianne.nordsmark@rm.dk

Hanna Mortensen, Dr.
E-Mail: Hanna.Mortensen@auh.rm.dk» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

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)

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. Pulmonary complications (Time Frame - from randomization until 90 days after surgery):
Incidence of pulmonary complications during and following nCPT or nCXT and surgery



Secondary outcome:

1. Early toxicity (Time Frame - from start of nCPT or nCXT until surgery):
Predefined items ≥ grade 2 scored by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

2. Late toxicity (Time Frame - up to 5 years):
Predefined items ≥ grade 2 scored by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

3. Postoperative complications (Time Frame - from surgery until 90 days after surgery):
Predefined items scored by Clavien-Dindo and Comprehensive Complications Index (CCI)

4. Major cardiovascular events (MACE) (Time Frame - up to 5 years):
Predefined cardiovascular events scored by MACE

5. Patient-reported outcome measures (Time Frame - up to 5 years):
EORTC quality of life questionnaire

6. Compliance with trimodality treatment (Time Frame - 3 months):
The proportion of patients complying with trimodality treatment in each arm

7. Pathological response (Time Frame - immediately after surgery):
tumor regression grade for the primary tumor scored according to Mandard score.

8. Cumulative incidence of loco-regional failure (Time Frame - from date of randomization up to 5 years):
Locoregional failure evaluated according to RECIST with all failures within the irradiated volume counting as events.

9. Pattern of failure (Time Frame - up to 5 years):
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.

10. Disease-free survival (DFS) (Time Frame - up to 5 years):
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.

11. Overall survival (OS) (Time Frame - up to 5 years):
Death from all causes will considered as events

Studien-Arme

  • Active Comparator: Photon Arm
    Standard arm with neoadjuvant chemoradiotherapy (nCXT) with photons
  • Experimental: Proton Arm
    Experimental arm with neoadjuvant chemoradiotherapy (nCPT) with protons

Geprüfte Regime

  • 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
  • Proton Radiotherapy (Proton Therapy):
    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

Quelle: ClinicalTrials.gov


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