Oncometabolome and MALDI-MSI in Upper GI Carcinomas - Chemosensitivity in Esophageal Carcinoma

NCT06642506 | Active Not Recruiting

• 1 other identifier: 24-0606
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Locally advanced adenocarcinoma of the esophagus is a leading cause of death from malignant disease in Germany and has been characterized on a molecular level in recent years. This retrospective observational study deals with patients after esophagectomy with different risk constellations of esophageal carcinoma. An early and individualized therapy of this tumor in an approach of precision oncology significantly improves the prognosis. The metabolomic profile plays a central role in tumor plasticity and oncological outcome. At the same time, these factors affect the efficacy of chemotherapy and need to be investigated in more detail at the molecular level. A central element of this study is the investigation of phospholipid metabolism locally in tumor tissue, in adjacent normal tissue in terms of the tumor microenvironment and systemically in blood plasma. The focus lies on the validation of known oncometabolites that significantly influence tumor sensitivity to chemotherapy. By combining mass spectrometry imaging using matrix-assisted laser desorption ionization - mass spectrometry imaging (MALDI-MSI) with metabolomics using liquid chromatography tandem mass spectrometry (LC-MS/MS), the metabolic profile of tumors can be analyzed in detail, allowing conclusions to be drawn about chemo-insensitive and therapeutically challenging tumors. Both mass spectrometric methods are used to understand the heterogeneous metabolism of the tumors and to describe possible constellations that are associated with increasing chemoresistance. For precise investigation, the cohort under investigation is divided into two patient collectives. Patients with a regression grade 1 after four sessions of FLOT chemotherapy are compared with a regression grade 3 according to Becker in the postoperative pathological assessment. This facilitates the development of personalized therapeutic approaches tailored to the individual oncological profiles of the tumors. The study is complemented by conventional HE microscopic examinations of the tumor itself and the tumor microenvironment, which allow to analyze the morphology and its correlation with metabolic alterations in the tissue. We hypothesize that adenocarcinoma of the esophagus with regression grade 1 encompasses a fundamentally distinct metabolic profile than adenocarcinoma of the esophagus with regression grade 3. Consequently, a stratification parameter within the local tumor metabolism and the tumor microenvironment exists, which correlates with the systemic response to neoadjuvant chemotherapy in blood plasma. The primary aim of the study is to create a comprehensive metabolic profile that clearly identifies tumors with a regression grade 1 versus a regression grade 3 according to Becker. This will be used to improve diagnostics and develop personalized treatment strategies that increase treatment efficiency and patients' chances of survival. This is ultimately carried out with the intention of achieving an improved survival rate and a higher quality of life for patients with locally advanced esophageal cancer. The comprehensive analysis of the tumor microenvironment and the morphological and metabolic profiles should provide new insights into the mechanisms of tumor progression and resistance, which in turn will form the basis for future translational research and treatment approaches. The findings from this study have the potential to change the way esophageal cancer is treated by contributing to the development of stratified therapeutic approaches tailored to the molecular subtype of esophageal cancer.

Conditions

Esophagus Adenocarcinoma; Esophagus Cancer; Metabolome; Mass Spectrometry; Precision Medicine; Oncology Patients Receiving Chemotherapy; Metabolomics; Chemoresistance

Keywords

Oncometabolome; Metabolomics; Mass Spectrometry Imaging; Esophagus Cancer; Chemosesitivity

Outcome Measures

Primary Outcomes (1)

• Oncometabolome

  The primary endpoint is the metabolome of the tumor tissue, with a particular focus on significant differences in the composition of membrane lipids, amino acids, and carbohydrates between the group "Regressions Grade 1" and "Regressions Grade 3"

  From enrollment to the end of treatment at 10 weeks

Secondary Outcomes (1)

• Mass spectrometry imaging of the metabolome

  From enrollment to the end of treatment at 10 weeks

Study Arms (3)

Primary resection

Patients with esophageal adenocarcinoma who underwent esophagectomy without prior neoadjuvant therapy.

Regression Grade 1

Patients with esophageal adenocarcinoma who received four cycles of neoadjuvant FLOT chemotherapy and subsequently underwent oncological esophagectomy. Final pathology revealed a regression grade of 1 according to the Becker classification.

Regressions Grade 3

Patients with esophageal adenocarcinoma who received four cycles of neoadjuvant FLOT chemotherapy and subsequently underwent oncological esophagectomy. Final pathology revealed a regression grade of 3 according to the Becker classification.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with histologically confirmed esophageal adenocarcinoma who may be eligible for primary resection or neoadjuvant chemotherapy with four cycles of FLOT followed by esophagectomy, following discussion in the interdisciplinary tumor board.

You may qualify if:

• Signed Written Informed Consent
• Study participants must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
• Study participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• Histologically confirmed, resectable adenocarcinoma of the esophagus (uT2, uN+, cM0 or uT3, cNx, cM0), with the following specifications:
• Medical and technical operability
• No preceding cytotoxic or targeted therapy
• No prior partial or complete tumor resection
• Male or female patients \> 18 years of age at time of study entry
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Life expectancy of at least 12 months
• Adequate normal organ function as defined below. Screening laboratory values must meet the following criteria and should be obtained within 28 days prior to registration
• WBC ≥ 1500/μL
• Neutrophils ≥ 1000/μL
• Platelets ≥ 75 x103/μL
• Hemoglobin \> 9.0 g/dL

You may not qualify if:

• Study participants with squamous cell carcinoma of the esophagus
• Prior treatment with chemotherapy, targeted therapy or radiotherapy for treatment of advanced cancer disease less than 5 years.
• Enrollment is possible for patients with:
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Any other serious or uncontrolled medical disorder, active infections, physical exam findings, laboratory finding, altered mental status, or psychiatric condition that, in the opinion of the investigator, would limit a study participant's ability to comply with the study requirements, substantially increase risk to the study participant, or impact the interpretability or study results
• Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients with celiac disease controlled by diet alone.
• Inhaled or topical steroids and adrenal replacement steroid doses \>10mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• History of active primary immunodeficiency
• History of any allogenic organ transplantation with currently intake of immune suppressive treatment
• Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. FEV 1 \< 75%

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• Max Planck Institute of Biochemistry, Department of Proteomics and Signal Transduction, München, Germany: collaborator
• Dr. von Haunersches Children's Medical Hospital, University of Munich, Germany: collaborator

Study Sites (1)

Department of General, Visceral and Transplantation Surgery, LMU University Hospital

Munich, Bavaria, 81377, Germany

Location

Related Publications (28)

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Tumortissue Adjacent normal tissue Blood Serum

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Ilja Balonov, Dr. med.

  Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Germany

  PRINCIPAL INVESTIGATOR

• Jens Werner, Prof. Dr. med.

  Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Germany

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 11, 2024
• First Posted: October 15, 2024
• Study Start: October 6, 2024
• Primary Completion: June 1, 2025
• Study Completion: September 1, 2025
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)