Clinical trial NCT05954117: Chemotherapy in the Context of Esophageal and Gastroesophageal Junction Cancer Cachexia
Official title: Effect of Chemotherapy on Metabolic Flexibility in the Context of Cachexia in Cancers of the Esophagus and Gastroesophageal Junction
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Esophageal Adenocarcinoma
Keywords: Mitochondria
Oxygraphy
Adipose Tissue
Gastroesophageal adenocarcinoma
Energy expenditure
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Université d'Auvergne
name: Centre de Recherche en Nutrition Humaine d'Auvergne
name: Ligue contre le cancer, France
First posted: 2023-07-20
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: patient undergoing surgery for esophageal adenocarcinoma or for gastroesophageal adenocarcinoma
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief 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.

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.

Primary outcomes:
measure: Evaluation of mitochondrial respiration on adipose tissue by oxygraphy
timeFrame: 6 week
Secondary outcomes:
measure: Evaluation of sarcopenia (SARC-F : sarcopenia scoring)
timeFrame: 1 week
measure: anthropometric data
timeFrame: 1 week
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
Study officials:
affiliation: Ruddy.Richard@Uca.Fr
name: Ruddy RICHARD
role: PRINCIPAL_INVESTIGATOR
References: