The Efficacy of Neoadjuvant Chemoradiotherapy in Comparison With Neoadjuvant Chemotherapy in Patients With Resectable Squamous Cell Esophageal Cancer

An Open-Label Randomized Clinical Trial to Evaluate the Efficacy of Neoadjuvant Chemoradiotherapy in Comparison With Neoadjuvant Chemotherapy in Patients With Resectable Squamous Cell Esophageal Cancer cT3-4aN0M0, cT1-4aN1-3M0.

The purpose of this study is to evaluate the safety, feasibility and outcomes of neoadjuvant chemotherapy followed by esophagectomy versus neoadjuvant chemoradiotherapy followed by esophagectomy for locally advanced resectable esophageal squamous cell carcinoma cT3-4aN0M0, cT1-4aN1-3M0. This is non-inferiority study (neoadjuvant chemoradiotherapy has no advantage over neoadjuvant chemotherapy).

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Procedure: Patients undergoing neoadjuvant chemoradiotherapy plus Ivory-Lewis or McKeown esophagectomy.; Procedure: Patients undergoing neoadjuvant chemotherapy plus Ivory-Lewis or McKeown esophagectomy

Detailed Description

It is a prospective open-label randomized phase III clinical trial sponsored by N.N. Blokhin NMRC of Oncology. 156 patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0M0, cT1-4aN1-3M0) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy group (nCRT) followed by esophagectomy and the neoadjuvant chemotherapy group (nCT) followed by esophagectomy according to the proportion of 1:1. The safety, efficacy of protocols and prognosis of patients are compared between the two regimens.

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Omar Abouhaidar, MD, PhD; Phone Number: +79269125902; Email: abouhaidar@yandex.ru
• Study Contact Backup: Name: Parvin Akhmedov; Phone Number: +79267333323; Email: Akhmedovparvin@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Recruiting
    • N.N. Blokhin National Medical Research Center of Oncology
    • Contact: Pavel Kononets
    • Principal Investigator: Pavel Kononets
    • Sub-Investigator: Omar Abouhaidar
    • Sub-Investigator: Parvin Akhmedov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent.
• Histologically confirmed squamous cell carcinoma of the esophagus.
• Clinical stage cT1-4aN1-3M0 (AJCC/UICC 8th Edition).
• Indications for surgical esophageal resection
• ECOG status 0-1.
• Adequate bone marrow function (White Blood Cells > 3.0 x 109/L; Neutrophil > 2.0 × 109/L; Hemoglobin > 90 g/L; Platelets > 100 x 109/L).
• Adequate liver function (Total bilirubin < 1.5 x Upper Level of Normal (ULN); Aspartate transaminase (AST) and Alanine transaminase (ALT) < 3.0 x ULN);
• Adequate renal function (Glomerular filtration rate (CCr) > 50 ml/min.
• Adequate cardiac function. Left ventricular ejection fraction > 50%.
• Age from 18 years to 70

Exclusion Criteria:

• Clinical stage cT4bcN0cM0 (AJCC/UICC 8th Edition).
• Patients with advanced non-operable or metastatic esophageal cancer.
• Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy.
• Patients with another previous or current malignant disease.
• Allergy or contraindications to Paclitaxel, Carboplatin, Docetaxel, Cisplatin or Fluoruracil.
• Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive.
• Severe concomitant diseases (uncontrolled arterial hypertension, diabetes mellitus, stroke less than 6 months old, mental disorders, other tumors, etc.).
• Clinically significant coronary artery disease (NYHA III / IV), congestive heart failure (NYHAIII / IV), clinically significant cardiomyopathy, myocardial infarction within the last 6 months, or high risk of uncontrolled arrhythmia.
• Chronic inflammatory diseases of the gastrointestinal tract
• Acute infectious diseases.
• Pregnancy or breast feeding.
• Serious concomitant physical and mental illness / abnormalities or territorial reasons that may prevent the patient from participating in the protocol and adherence to the protocol schedule.
• Foreigners or persons with limited legal rights.
• Any medical, geographic, or social circumstance, that in the opinion of the investigator excludes the patient's participation in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Neoadjuvant Chemoradiotherapy; Carboplatin (AUC 2 mg/mL per min) and Paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. A total radiation dose of 41,4 Gy was given in 23 fractions of 1,8 Gy, 5 days per week. After neoadjuvant therapy, patients receive Ivor-Lewis or Mckeown Esophagectomy.	Procedure: Patients undergoing neoadjuvant chemoradiotherapy plus Ivory-Lewis or McKeown esophagectomy.; Patients undergoing neoadjuvant chemoradiotherapy plus Ivory-Lewis or McKeown esophagectomy.
EXPERIMENTAL: Neoadjuvant Chemotherapy; 4 cycles of DCF regimen (docetaxel 75 mg/m2 day, CDDP 75 mg/m2 and 5FU at 750 mg/m2/ day for 5 days) every 3 weeks. Patients with dysphagia 3 оr with weight loss more then 10% 6 cycles of modified-DCF regimen will be performed (mDCF, docetaxel 50 mg/m2 day, CDDP 50 mg/m2 day and 5-FU at 2400 mg/m2/day for 2 days) every 3 weeks. After neoadjuvant therapy, patients receive Ivor-Lewis or Mckeown Esophagectomy.	Procedure: Patients undergoing neoadjuvant chemotherapy plus Ivory-Lewis or McKeown esophagectomy; Patients undergoing neoadjuvant chemotherapy plus Ivory-Lewis or McKeown esophagectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Survival without local or systemic recurrence	3(5) years after last patient enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival of patients	3(5) years after last patient enrolled
Treatment related complications	Сomplications after treatment	During the procedure
Number of cycles, frequency of neoadjuvant therapy reduction	Number of chemotherapy/chemoradiotherapy cycles and doses and dose reductions	During the procedure
Correlation between genetic profile and tumor response	Influence of the genetic profile on the tumor response	Immediately after the procedure
Pathological response rate(pCR)	Frequency of pathological pathomorphosis	Immediately after the surgery
R0 resection rate	Residual tumor rate	Immediately after the surgery

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 14, 2022
• Primary Completion (ANTICIPATED): September 14, 2025
• Study Completion (ANTICIPATED): September 14, 2027

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 19, 2022
• First Posted (ACTUAL): September 21, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 2, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: ENCHENEC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are not planning to share personal patient data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No