Total Neoadjuvant FLOT Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer

NCT ID: NCT06028737

Last Updated: 2025-05-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-25
• Study Completion Date: 2032-12-31

Brief Summary

The main goal of this study is to investigate the proportion of participants with locally advanced gastric and gastroesophageal adenocarcinoma without previous treatment during the last 5 years who can tolerate all planned cycles of chemotherapy and radical surgical treatment who will be prospectively randomized into two groups to undergo one of two chemotherapy regimens, followed by surgery:

1. 8 cycles of Total Neoadjuvant ChemoTherapy (TNT) with 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin, and Docetaxel (FLOT) followed by surgery.

2. 4 cycles of Neoadjuvant FLOT chemotherapy scheme preoperatively and 4 adjuvant FLOT cycles postoperatively.

Detailed Description

This is a multi-center international European prospective randomized study that aims to enroll participants with resectable locally advanced gastric and gastroesophageal (Siewert 2, 3) adenocarcinoma (≥cT3 and/or ≥cN0 and M0) with no history of previous oncological treatment during the last five years, who 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 randomized to the first (control) group will receive eight cycles of the perioperative FLOT chemotherapy scheme: 4 cycles before surgical treatment and four cycles after surgical intervention. Patients randomized to the second (study) group will receive eight cycles of FLOT total neoadjuvant chemotherapy, followed by surgery.

The study's primary endpoint is the proportion of patients receiving all planned chemotherapy cycles and radical surgical treatment. 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; composition and biomarkers of gut microbiota; objective tumor response.

Based on previous studies, with the current standard treatment protocol-four cycles of FLOT chemotherapy before surgery and four cycles after-only 47% of patients complete all eight cycles. In contrast, with total neoadjuvant therapy, where the entire chemotherapy regimen is administered before surgery, 71% of patients are able to complete all eight FLOT cycles.

Given these findings, it was calculated that to ensure 80% study power with a two-sided 5% significance level, each study group should include 65 participants. Considering an expected dropout rate of 15%, a total of 150 patients will be recruited. Up to 40 patients will be enrolled in Vilnius, Lithuania, with the remaining participants recruited in Kyiv, Ukraine.

Conditions

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; Chemotherapy; Gastrectomy; Gastrectomy for Gastric Cancer; Gastric Resection; Gastric (Cardia, Body) Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Perioperative 4+4 FLOT cycles

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

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

50mg/m2, d1, i.v., every 2 weeks

Oxaliplatin

Intervention Type: DRUG

85 mg/m², d1, i.v., every 2 weeks

Leucovorin

Intervention Type: DRUG

200 mg/m², d1, i.v., every 2 weeks

Fluorouracil

Intervention Type: DRUG

2600 mg/m²d1 i.v. every 2 weeks

Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles

8 cycles of total neoadjuvant FLOT chemotherapy regimen, followed by surgery.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

50mg/m2, d1, i.v., every 2 weeks

Oxaliplatin

Intervention Type: DRUG

85 mg/m², d1, i.v., every 2 weeks

Leucovorin

Intervention Type: DRUG

200 mg/m², d1, i.v., every 2 weeks

Fluorouracil

Intervention Type: DRUG

2600 mg/m²d1 i.v. every 2 weeks

Interventions

Docetaxel

50mg/m2, d1, i.v., every 2 weeks

Intervention Type: DRUG

Oxaliplatin

85 mg/m², d1, i.v., every 2 weeks

Intervention Type: DRUG

Leucovorin

200 mg/m², d1, i.v., every 2 weeks

Intervention Type: DRUG

Fluorouracil

2600 mg/m²d1 i.v. every 2 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Tumor spread according to TNM: ≥cT3 and/or ≥cN0 and M0 (except of invasion of the common hepatic artery, celiac trunk, proximal part of the splenic artery, aorta, head of the pancreas);
• Performance status by Eastern Cooperative Oncology Group (ECOG): 0 - 1;
• Histologically confirmed gastric adenocarcinoma or gastroesophageal junction (Siewert type 2/3) 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;
• Patient agrees to participate in this biomedical study.

Exclusion Criteria

• Presence of another oncological disease at a different site if less than 5 years have passed since radical treatment.
• Comorbidities or patient conditions that preclude the administration of chemotherapy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ukrainian Society of Clinical Oncology

OTHER

Sponsor Role: lead

Responsible Party

Mykyta Pepenin

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mykyta Pepenin, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Cancer Institute

Vilnius, , Lithuania

Site Status: RECRUITING

National Cancer Institute

Kyiv, , Ukraine

Site Status: RECRUITING

Countries

Lithuania; Ukraine

Central Contacts

Mykyta Pepenin, MD

Role: CONTACT

pepenin95@gmail.com

+380959448858

Oleksii Dobrzhanksiy, MD

Role: CONTACT

alekseydobrzhanskiy@gmail.com

+380638760185

Facility Contacts

Augustinas Baušys, MD, PhD

Role: primary

abpelikanas@gmail.com

+37062363865

Mykyta Pepenin, MD

Role: primary

pepenin95@gmail.com

+380959448858

Andrii Horodetskiy

Role: backup

gorodeckij03@gmail.com

+380990864410

Other Identifiers

241/4

Identifier Type: -

Identifier Source: org_study_id