Total Neoadjuvant Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer

Gastric Cancer Clinical Trial

— OCTASUR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06028737
• Other study ID #: 241/4
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 25, 2023
• Est. completion date: December 2031

Study information

• Verified date: August 2023
• Source: Ukrainian Society of Clinical Oncology
• Contact: Mykyta Pepenin, MD
• Phone: +380959448858
• Email: pepenin95[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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:

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 758
• Est. completion date: December 2031
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Tumor spread: ?T3, ?T4a, ??4b (except of invasion of the common hepatic artery, celiac trunk, proximal part of the splenic artery, aorta, head of the pancreas); ?N1, ?N2, ?N3; ?M0;

• 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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Gastric Adenocarcinoma
• Advanced Gastric Carcinoma
• Advanced Gastroesophageal Junction Adenocarcinoma
• Esophageal Neoplasms
• Gastric Adenocarcinoma
• Gastric Cancer
• Gastric Neoplasm
• GastroEsophageal Cancer
• Gastroesophageal Junction Adenocarcinoma
• Gastrointestinal Cancer
• Gastrointestinal Neoplasms
• Neoplasms
• Stomach Cancer
• Stomach Neoplasm
• Stomach Neoplasms

Intervention

Drug:
• Docetaxel
50mg/m2, d1, i.v., every 2 weeks
• Oxaliplatin
85 mg/m², d1, i.v., every 2 weeks
• Leucovorin
200 mg/m², d1, i.v., every 2 weeks
• Fluorouracil
2600 mg/m²d1 i.v. every 2 weeks

Locations

Country	Name	City	State
Ukraine	National Cancer Institute	Kyiv

Sponsors (1)

Lead Sponsor	Collaborator
Ukrainian Society of Clinical Oncology

Country where clinical trial is conducted

Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histopathological tumor response rate (Becker regression criteria).	To determine the pathohistological regression rate after 8 FLOT cycles in total neoadjuvant regimen compared to 4 FLOT cycles in neoadjuvant regimen.	14 days after surgery
Secondary	Surgical complications rate.	To determine postoperative surgical complications rate and profile after the different chemotherapy regimens, according to Clavien-Dindo classification.	30 days after surgery.
Secondary	Chemotherapy toxicity rate and profile.	To determine chemotherapeutic toxicity profile, according to Common Terminology Criteria for Adverse Events (CTCEA 5.0).	At the end of each FLOT cycle (each cycle is 14 days), up to 14 days after the last cycle.
Secondary	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.	24 months.
Secondary	Disease-free survival.	To determine the efficacy of total neoadjuvant FLOT regimen compared to perioperative FLOT regimen.	1 year after the last intervention.
Secondary	Median overall survival.	To determine the efficacy of TNT FLOT regimen compared to perioperative FLOT regimen by assessment of overall survival.	5 years follow-up after the last intervention.
Secondary	Correlation between the pathohistological response and overall and disease-free survival.	To determine the correlation between the pathohistological response and overall and disease-free survival.	14 days after surgery.