Chemotherapy in the Context of Esophageal and Gastroesophageal Junction Cancer Cachexia

Trial Title: Chemotherapy in the Context of Esophageal and Gastroesophageal Junction Cancer Cachexia

NCT ID: NCT05954117

Condition: Esophageal Adenocarcinoma

Conditions: Official terms:
Adenocarcinoma
Cachexia

Conditions: Keywords:
Mitochondria
Oxygraphy
Adipose Tissue
Gastroesophageal adenocarcinoma
Energy expenditure

Study type: Interventional

Study phase: N/A

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: patient undergoing surgery for esophageal adenocarcinoma or for gastroesophageal adenocarcinoma

Primary purpose: Health Services Research

Masking: None (Open Label)

Intervention:

Intervention type: Procedure
Intervention name: Adipose tissue biopsies
Description: During the 2 surgical time, when patient is under general anesthesia, two adipose tissue biopsies of 20cc each (one from abdominal subcutaneous adipose tissue and one from omental adipose tissue) are taken and characterize by oxygraphy (respirometry). Before the 2 surgical times (before and after chemotherapy) patients will have evaluation of the muscle strength, cachexia (by scan analysis), energy expenditure, anthropometric criteria and biochemical inflammatory.
Arm group label: Interventional

Summary: Cachexia is a syndrome frequently associated with digestive cancers and more particularly with esophageal and gastroesophageal adenocarcinoma. Its pathophysiology remains poorly understood, multi-factorial, but strongly correlated to the prognosis of patients. It's a consequence of the imbalance of energy balance linked to tumoral process, to dysphagia and to anorexia, frequently present in these cancers. At the center of this imbalance, adipose tissue plays a major role. Recent studies showing that the mobilization of lipid substrates and the hypermetabolism of adipocytes are involving in its development, even before loss of muscle. As part of the management, neoadjuvant chemotherapy is usually administered with the main objective to reduce tumor extension and dissemination through actions on DNA and mitosis. These treatments will also alter the mitochondrial function of cells in other tissues, probably including that of adipocytes. A paradoxical effect on the cachectic process could thus be envisaged, as a decrease in mitochondrial activity and associated hypermetabolism, and therefore a preservation of fat mass, and by extension of muscle mass. Primary endpoint: identify the adipocyte factors involved in the energy imbalance associated with the cachectic process in patients managed for esophageal or gastroesophageal adenocarcinoma. Secondary endpoint: compare the results obtained before and after chemotherapy treatment according to the cachectic state and the anatomical location of the adipose sample (subcutaneous versus visceral) to evaluate the resting energy expenditure.

Detailed description: Two operative steps, separated by neoadjuvant chemotherapy, are classically planned in the management of esophageal and gastroesophageal adenocarcinoma: an exploratory laparoscopy as part of the disease extension assessment and the tumor resection surgery (esophagectomy). During these operations, the surgeon will perform a subcutaneous fat biopsy at the surgical approach and a visceral fat biopsy at the epiploic level. A portion of the samples will be immediately analyzed by high-resolution oxygraphy to evaluate the mitochondrial metabolism of the adipocytes. The rest of biopsies will be frozen for further biological analysis (enzymology, Western-blot, RT-qPCR) or embedded in paraffin for histological analysis (morphometry, inflammation, metabolism). Serum will also be recovered with the biopsies for specific biological analysis (inflammatory and lipid status). In days preceding the interventions, in addition to the usual management, will be performed: an evaluation of the energy expenditure by indirect calorimetry, an evaluation of the body composition by Dual Energy X-ray Absorptiometry (DEXA), physical tests to evaluate sarcopenia and cachexia, nutritional and quality of life questionnaires, and a medical examination with a dietetic consultation.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Male Patients - Patients aged over 18 - Patients eligible for neoadjuvant FLOT chemotherapy (5-fluorouracil, oxaliplatin, docetaxel); - Patients with a resealable adenocarcinoma of esophageal or gastroesophageal - Patients able to give informed consent. - Patients affiliated to a Health Care insurance Exclusion Criteria: - Unresectable or metastatic esophageal or gastroesophageal adenocarcinoma; - Another tumor histology than adenocarcinoma. - Patients not eligible for neoadjuvant FLOT chemotherapy and/or for surgery - Patients under guardianship, curators or deprived of liberty; - Refusal to participate; - Patients already participating in another interventional study of pharmacological, nutritional and/or rehabilitation study; - Patients in a period of exclusion from another research protocol.

Gender: Male

Minimum age: 18 Years

Maximum age: 99 Years

Healthy volunteers: No

Locations:

Facility:
Name: CHU de Clermont-Ferrand

Address:
City: Clermont-Ferrand
Zip: 63000
Country: France

Start date: July 25, 2023

Completion date: September 2026

Lead sponsor:
Agency: University Hospital, Clermont-Ferrand
Agency class: Other

Collaborator:
Agency: Université d'Auvergne
Agency class: Other

Collaborator:
Agency: CRNH Auvergne
Agency class: Other

Collaborator:
Agency: Ligue contre le cancer, France
Agency class: Other

Source: University Hospital, Clermont-Ferrand

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05954117