Exploring the role of the microbiome in gastroesophageal tumors

Dissecting the Role of MIcrobioMe in gastroEsophageal Tumor: a multIdisCiplinary Longitudinal Study

This study looks at how the bacteria in the gut might affect the growth of gastroesophageal cancer and how well treatments work for patients with this type of tumor.

Quick facts

• Study type: Observational
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: European Institute of Oncology (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 1 site (Milan)
• Trial ID: NCT06405035 on ClinicalTrials.gov

What this trial studies

This observational study investigates the role of the microbiome in patients with gastroesophageal adenocarcinoma. It aims to understand how dietary, lifestyle, and environmental factors may influence cancer growth and treatment outcomes. Patients with histologically confirmed resectable tumors will be monitored over time, with a focus on collecting tissue samples and assessing prognostic factors. The study seeks to uncover molecular mechanisms underlying cancer invasiveness and the potential predictive power of these factors in treatment planning.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed Stage Ib to Stage III resectable gastroesophageal adenocarcinoma.

Not a fit: Patients with non-resectable tumors or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved prognostic and predictive factors for tailoring treatments in gastroesophageal adenocarcinoma.

How similar studies have performed: While the role of the microbiome in cancer is an emerging field, this specific approach to gastroesophageal tumors is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Patients must have histologically confirmed 8th ed. American Joint Committee on Cancer (AJCC) Stage Ib to Stage III resectable GEA. A multidisciplinary discussion within surgical oncologists, medical oncologists, and radiologist will assess the disease resectability.
2. Signed Written Informed Consent.
3. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and all protocol procedures.
4. Males and Females, ages ≥18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
6. Have measurable disease based on RECIST 1.1.
7. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion and normal mucosa at baseline and at the time points specified in the Study Procedure Tables.
8. Patients must be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team.
9. Demonstrate adequate organ function as defined below: Hematologic Absolute neutrophil count (ANC) \>/= 1.5 X 10\^9/L; Hemoglobin \>/= 9.0 g/dL Platelets \>/= 100 X 10\^9/L prothrombin time (PT)/ international normalized ratio (INR) and partial thromboplastin timePTT \</= 1.5 X ULN. Hepatic Total bilirubin \</= 1.5 X upper limit normal ULN (isolated bilirubin \>1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) aspartate aminotransferase AST and alanine aminotransferase ALT Albumin \</= 2.5 X ULN 1 \>/=2.5 g/dL Renal Creatinine OR Calculated creatinine clearance OR 24-hour urine creatinine clearance \</=1.5 X ULN 2 \>/= 50 mL/min \>/= 50 mL/min.
10. Women are eligible to participate if: non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 mlU/mL and estradiol \< 40 pg/mL (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT.
11. The individual methods of contraception and duration should be determined in consultation with the investigator. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
12. Women must not be breastfeeding.
13. Men who are sexually active must use any contraceptive method with a failure rate of less than 1% per year. The investigator shall review contraception methods and the time period that contraception must be followed.
14. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception.

Exclusion Criteria:

1. Previously or currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
2. Any major surgery within the last 3 weeks.
3. Stage IV disease at diagnosis.
4. Pregnant or lactating female.
5. Unwillingness or inability to follow the procedures required in the protocol.
6. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
7. Prior malignancy active within the previous 2 years except for patient's prior diagnosis locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast with local control measures (surgery, radiation).
8. Patients with active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
9. Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
10. Patients with a condition requiring systemic treatment with antibiotic or antimycotic medications within 8 weeks from the surgery.
11. Any positive test result for hepatitis B or C virus indicating acute or chronic infection.
12. Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome.
13. Patients who are compulsorily detained for treatment of either a psychiatric or physical (infection disease) illness.

Where this trial is running

Milan

• European Institute of Oncology — Milan, Italy (Recruiting)

Study contacts

• Principal investigator: Chiara Alessandra Cella, MD — Istituto Europeo di Oncologia
• Study coordinator: Chiara Alessandra Cella, MD

Conditions Adenocarcinoma; gastroesohageal adenocarcinoma; neoadjuvant chemotherapy; microbiome; radiomics; predictive factor; risk factor; nutrition