Chemotherapy in the Context of Esophageal and Gastroesophageal Junction Cancer Cachexia

NCT ID: NCT05954117

Last Updated: 2023-07-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-25
• Study Completion Date: 2026-09-30

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.

Conditions

Esophageal Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Interventional

patients with esophageal or gastroesophageal adenocarcinoma included to evaluate the energy expenditure before and after chemotherapy and evaluate parameters of cachexia

Group Type: EXPERIMENTAL

Adipose tissue biopsies

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Université d'Auvergne

OTHER

Sponsor Role: collaborator

Centre de Recherche en Nutrition Humaine d'Auvergne

OTHER_GOV

Sponsor Role: collaborator

Ligue contre le cancer, France

OTHER

Sponsor Role: collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ruddy RICHARD

Role: PRINCIPAL_INVESTIGATOR

Ruddy.Richard@Uca.Fr

Locations

CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Countries

France

Central Contacts

Lise LACLAUTRE

Role: CONTACT

promo_interne_drci@chu-clermontferrand.fr

334.73.754.963

References

Bacoeur-Ouzillou O, Guerrier L, Touron J, Pinel A, Pereira B, Meunier N, Gillet B, Pezet D, Cassagnes L, Malpuech-Brugere C, Richard R, Gagniere J. Chemotherapy effects on mitochondrial function in adipose tissue in oesophageal and gastroesophageal junction adenocarcinomas with or without associated cachexia: protocol for a prospective, comparative observational study (ChiFMeOE). BMJ Open. 2024 Oct 23;14(10):e086686. doi: 10.1136/bmjopen-2024-086686.

Reference Type: DERIVED

PMID: 39448207 (View on PubMed)

Other Identifiers

2023-A00582-43

Identifier Type: OTHER

Identifier Source: secondary_id

AOI 2022 RICHARD

Identifier Type: -

Identifier Source: org_study_id