Irinotecan-based Triplet (FOLFOXIRI) as Perioperative Treatment in Resectable Gastric and Gastroesophageal Junction Adenocarcinoma.

Study Overview
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Brief Summary
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In this clinical trial, patients with gastric and gastroesophageal junction adenocarcinoma will be included. Treatment with curative intent will be given with chemotherapy for 4 cycles with fluorouracil, oxaliplatin and irinotecan preoperatively followed by surgery, and then additionally 4 cycles of the same chemotherapy postoperatively. The standard treatment today is preoperative treatment with fluorouracil and oxaliplatin pre-and postoperatively. The rationale for this trial is, that the addition of irinotecan might improve treatments results.

Official Title
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Irinotecan-based Triplet (FOLFOXIRI) as Perioperative Treatment in Resectable Gastric and Gastroesophageal Junction Adenocarcinoma.

Conditions
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Resectable Gastric and Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: Fluorouracil
* Drug: Oxaliplatin
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified, resectable gastric or gastroesophageal (GE) (gastroesophageal) junction (Siewert type I-III) adenocarcinoma Confirmation of patient operability by surgeon Primary tumor, regional nodes, metastasis (TNM), 8th edition): cT2-4a or cN+, cM0 Age: 18 years or older World Health Organization (WHO) performance status ≤ 1 Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy Adequate laboratory findings: hematological: hemoglobin > 90 g/L (transfusion is allowed to attain this), absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 75 x 109/L hepatic: bilirubin ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALAT) ≤ 3 x ULN renal: creatinine ≤ 1.5 x ULN (upper limit of normal) Fertile men and women must use highly effective means of contraception (failure rate <1%) such as: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal administration) progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable administration) intrauterine device intrauterine hormone-releasing system bilateral tubal occlusion vasectomised partner sexual abstinence Signed written informed consent The patient must be able to comply with the protocol Exclusion Criteria: Neuroendocrine or adenosquamous carcinoma Prior oncological treatment or surgical resection for the present disease Presence of other concurrent malignancies or previous malignancies within 5 years except for adequately treated basal or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix uteri Clinically significant (i.e. active) cardiovascular disease e.g. myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade III-IV congestive heart failure Active inflammatory bowel disease Symptomatic peripheral neuropathy greater than grade 1 (CTCAE version 4.03) Known hypersensitivity to any contents of the study drugs Pregnancy (positive pregnancy test) and/or breast feeding Any other serious or uncontrolled illness which in the opinion of the investigator makes it undesirable for the patient to enter the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with chemotherapy pre- and postoperative.<br> | Drug: Fluorouracil<br>* Treatment with Fluorouracil, Oxaliplatin, and Irinotecan is given for 4 cycles pre- and postoperatively, in total 8 cycles.<br>Drug: Oxaliplatin<br>* Treatment with Fluorouracil, Oxaliplatin, and Irinotecan is given for 4 cycles pre- and postoperatively, in total 8 cycles.<br>Drug: Irinotecan<br>* Treatment with Fluorouracil, Oxaliplatin, and Irinotecan is given for 4 cycles pre- and postoperatively, in total 8 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the rate of histopathological response according to Becker criteria. | Assessment of histopathological response, ypTNM, resection margin and residual tumor status. If Laurén classification and mismatch repair (MMR) or microsatelite instability status (MSI) could not be assessed on pretreatment biopsies it should be assessed on the resected specimen. Results do not have to be awaited before start of chemotherapy. | After surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric adenocarcinoma, Gastroesophageal junction adenocarcinoma, Chemotherapy, Fluorouracil, Oxaliplatin, Irinotecan, Preoperative chemotherapy, Postoperative chemotherapy, Histopathological response, Rate of R0-resection