Total Neoadjuvant Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer (OCTASUR)

Total Neoadjuvant Chemotherapy With 5-fluoruracil, Leucovorin, Oxaliplatin and Docetaxel in Locally Advanced Gastric and Gastroesophageal Junction Cancer (OCTASUR): Randomized, Single Center, Open Label Trial, Phase 2/3

The main goal of this study is to investigate the histopathological regression rate in patients with locally advanced gastric and gastroesophageal adenocarcinoma without previous treatment who will be prospectively randomized into two groups to undergo one of two chemotherapy regimens, followed by surgery: 8 cycles of Total Neoadjuvant ChemoTherapy (TNT) with 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Docetaxel (FLOT) followed by surgery. 4 cycles of Neoadjuvant FLOT chemotherapy scheme preoperatively and 4 adjuvant FLOT cycles postoperatively.

758 participants with resectable locally advanced gastric and gastroesophageal (Siewert 2, 3) adenocarcinoma (T3-4b, N1-3, M0) with no history of previous treatment will be included in this study after reading and signing the informed consent. After the initial diagnostic laparoscopy, patients will be randomized into two groups in a 1:1 ratio, with allocation to one of the two study groups. Patients who will be randomized to the first (control) group will receive 8 cycles of perioperative FLOT chemotherapy scheme: 4 cycles before surgical treatment and 4 cycles after surgical intervention. Patients who will be randomized to the second (study) group will receive 8 cycles of FLOT total neoadjuvant chemotherapy, followed by surgery. Primary endpoint of the study is pathomorphological tumor response rate. Secondary endpoints are: perioperative morbidity and mortality (surgical and chemotherapeutic complications); disease-free survival (DFS) and 1-, 3- and 5-years overall survival (OS); quality of life during and after the treatment; correlation between the pathohistological response and chemotherapy regimen.

Gastric Cancer, Stomach Cancer, GastroEsophageal Cancer, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Advanced Gastric Adenocarcinoma, Gastric Neoplasm, Stomach Neoplasm, Gastrointestinal Cancer, Advanced Gastroesophageal Junction Adenocarcinoma, Advanced Gastric Carcinoma

Total neoadjuvant chemotherapy, FLOT, Fluoruracil, Gastrectomy, Perioperative chemotherapy, Docetaxel, Leucovorin

4 cycles of neoadjuvant FLOT chemotherapy scheme, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy scheme.

To determine the pathohistological regression rate after 8 FLOT cycles in total neoadjuvant regimen compared to 4 FLOT cycles in neoadjuvant regimen.

To determine postoperative surgical complications rate and profile after the different chemotherapy regimens, according to Clavien-Dindo classification.

To determine chemotherapeutic toxicity profile, according to Common Terminology Criteria for Adverse Events (CTCEA 5.0).

Quality of patients' life, according to the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-30, QLQ-OG25).

To determine quality of life during the chemotherapy in both groups, after the surgery and 2 years follow-up after the completion of treatment, using EORTC QLQ-30, QLQ-OG25 questionnaires.

To determine the efficacy of TNT FLOT regimen compared to perioperative FLOT regimen by assessment of overall survival.

To determine the correlation between the pathohistological response and overall and disease-free survival.

Inclusion Criteria: Tumor spread: сT3, сT4a, сТ4b (except of invasion of the common hepatic artery, celiac trunk, proximal part of the splenic artery, aorta, head of the pancreas); сN1, сN2, сN3; сM0; Performance status by Eastern Cooperative Oncology Group (ECOG): 0 - 1; Histological type of tumor: adenocarcinoma; Differentiation grade: G0 - G4; Tumor localization: cardio-esophageal junction (Siewert 2, 3), cardiac part of the stomach, body of the stomach, antral part of the stomach, pyloric part of the stomach; Tumor extension: esophagus, diaphragm, liver, body and tail of the pancreas, anterior abdominal wall, small and large intestine, distal part of the splenic artery, spleen; No history of cancer in the past 5 years; Absence of previous chemotherapeutic, surgical or radiation treatment for oncological disease; No concomitant severe comorbidity; Patient willing to participate. Exclusion Criteria: M1 (distant metastases); ECOG 2 - 4; Age over 80 and under 18; Concomitant severe comorbidity; Refusal of the patient to participate in the study.

After the initial publication every participant will receive all the data to provide further data exploration.