Chemotherapy in the Context of Esophageal and Gastroesophageal Junction Cancer Cachexia

Esophageal Adenocarcinoma Clinical Trial

— CHIFMEOE  

Official title:

Effect of Chemotherapy on Metabolic Flexibility in the Context of Cachexia in Cancers of the Esophagus and Gastroesophageal Junction

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05954117
• Other study ID #: AOI 2022 RICHARD
• Secondary ID: 2023-A00582-43
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 25, 2023
• Est. completion date: September 2026

Study information

• Verified date: June 2023
• Source: University Hospital, Clermont-Ferrand
• Contact: Lise LACLAUTRE
• Phone: 334.73.754.963
• Email: promo_interne_drci[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: September 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Cachexia
• Esophageal Adenocarcinoma

Intervention

Procedure:
• Adipose tissue biopsies
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.

Locations

Country	Name	City	State
France	CHU de Clermont-Ferrand	Clermont-Ferrand

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand	CRNH Auvergne, Ligue contre le cancer, France, Université d'Auvergne

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of mitochondrial respiration on adipose tissue by oxygraphy	Evaluation of mitochondrial respiration on adipose tissue before and after chemotherapy Mitochondrial respiration measurements in oxydo-phosphorylated conditions. For each patient measurements using ADP and carbohydrate or lipid substrates of the respiratory chain complexes for both the subcutaneous and the visceral tissue.	6 week
Secondary	Evaluation of sarcopenia (SARC-F : sarcopenia scoring)	level of sarcopenia between 0 to 12 including 5 questions	1 week
Secondary	anthropometric data	BMI will be measured	1 week