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

NCT06405035 | Recruiting

• 1 other identifier: IEO-1440
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Gastric cancer (GC) is the second leading cause of cancer mortality and remains the fourth common cancer worldwide. Gastric and esophageal cancers treated with curative intent both have a poor prognosis with five-year survival rate varying between 30% and 40% \[Hagen\]. Therefore, even in the localized or locally advanced (LA) disease, relapse-related death remains a major challenge for curative treatment. Currently, there are several strategies for the curative treatment of GC including perioperative chemotherapy (peri-Op cht), adjuvant chemotherapy and adjuvant chemoradiotherapy. Despite the therapeutic management of localized or LA GC is well established, there is uncertainty about the power of prognostic and predictive factors to tailor anticancer treatments. In addition to that, further investigation is needed to investigate if pre-existing environment factors may act on carcinogenesis and to explore the molecular mechanisms that underlying cancer growth and invasiveness.

Conditions

Adenocarcinoma

Keywords

gastroesohageal adenocarcinoma; neoadjuvant chemotherapy; microbiome; radiomics; predictive factor; risk factor; nutrition; genomics; patient-centric model

Outcome Measures

Primary Outcomes (1)

• Tumor regression grading (TRG) system

  Tumor regression grading (TRG) system, which aims to categorize the amount of regressive changes after cytotoxic treatment mostly refer onto the amount of therapy induced fibrosis in relation to residual tumor or the estimated percentage of residual tumor in relation to the previous tumor site. Commonly used TRGs for upper gastrointestinal carcinomas are the Mandard grading and the Becker grading system. We will apply the Backer grading system.

  4 years

Secondary Outcomes (7)

• Pathological complete response (pCR)

  4 years

• Relapse free survival (RFS)

  4 years

• Past Nutrition

  4 years

• Nutrition risk screening

  4 years

• Nutrition status

  4 years

Study Arms (1)

patients with resectable gastroesohageal adenocarcinoma

patients with resectable GEA (including Siewert I) which are candidate to receive either peri-op treatments or upfront surgery followed by adjuvant treatments, if recommended.

Eligibility Criteria

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

Study Population

The study will be conducted in approximately 130 patients with resectable GEA (from stage IB to III according to TNM VIII edition) who are going to receive upfront surgery or peri-operative management. In the peri-operative cohort, treatments entail a 2 month-period of systemic therapy with FLOT or weakened regimens (i.e. FOLFOX, CAPOX), according to local practice. Surgery will be performed if restaging demonstrates a resectable disease. The choice of access route and type of operation will be chosen according to tumor site and stage, and according to patients' general conditions. Both open and minimally invasive techniques will be used as indicated.

You may qualify if:

• 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.
• Signed Written Informed Consent.
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and all protocol procedures.
• Males and Females, ages ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Have measurable disease based on RECIST 1.1.
• 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.
• Patients must be medically fit enough to undergo surgery as determined by the treating medical and surgical oncology team.
• 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.
• 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.
• 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.
• Women must not be breastfeeding.
• 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.
• Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception.

You may not qualify if:

• Previously or currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
• Any major surgery within the last 3 weeks.
• Stage IV disease at diagnosis.
• Pregnant or lactating female.
• Unwillingness or inability to follow the procedures required in the protocol.
• 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.
• 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).
• 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.
• 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.
• Patients with a condition requiring systemic treatment with antibiotic or antimycotic medications within 8 weeks from the surgery.
• Any positive test result for hepatitis B or C virus indicating acute or chronic infection.
• Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome.
• Patients who are compulsorily detained for treatment of either a psychiatric or physical (infection disease) illness.

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

European Institute of Oncology

Milan, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood samples, tissue samples, salivary swabs and fecal samples

MeSH Terms

Conditions

Adenocarcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Chiara Alessandra Cella, MD

  Istituto Europeo di Oncologia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chiara Alessandra Cella, MD

CONTACT

+390257489258; divisione.gastrointestinale@ieo.it

Cristina Mazzon

CONTACT

cristina.mazzon@ieo.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2024
• First Posted: May 8, 2024
• Study Start: March 8, 2022
• Primary Completion: March 8, 2025
• Study Completion: March 8, 2026
• Last Updated: May 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)