Perioperative Chemotherapy in Gastric Cancer (PECORINO)

Treatment Discontinuation Associated With Perioperative Toxicity of FLOT Versus XELOX Chemotherapy in Patient With Resectable Gastric Cancer; Phase 2

Patients with resectable adenocarcinoma of stomach or esophagogastric junction without previous therapy will be treated with one of two chemotherapy regimens perioperatively. One group of the patients will receive 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Docetaxel (FLOT), the second group will receive Oxaliplatin and Capecitabin (XELOX). Primary endpoint of the study is the proportion of patients who complete all allocated treatment.

Study Overview

• Status: Terminated
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Fluorouracil

Detailed Description

328 рatients with resectable (T1b-4 and/or N-/+, M0) adenocarcinoma of the stomach or the esophagogastric junction without previous therapy will be included in this study. After staging laparocopy patients will be randomized to receive preoperatively 4 cycles FLOT or 4 cycles XELOX followed by curative surgery. Adjuvant chemotherapy will be given as 4 cycles of FLOT or 4 cycles XELOX. The primary endpoint is the proportion of patients who fully adhered to all the allocated treatment per protocol. Secondary endpoints are pathological regression grade, progression free survival, overall survival, chemotherapy and surgery complications rates.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine, 03022
    • National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• cT1b-T4b (cT4b - invasion in diaphragm, parenchyma of liver, spleen, pancreas, abdominal wall, small bowel, colon, distal part of splenic artery)
• cN0-3
• M0
• Age: 18 - 80
• ECOG: 0 - 1
• Histological type: adenocarcinoma
• Differentiation grade: G0 - G4
• No previous surgery
• No previous chemotherapy
• No concomitant severe comorbidity
• Written informed consent

Exclusion Criteria:

• cT1a, cT4b (invasion in truncus, hepatic artery, proximal part of splenic artery)
• Presense of distant metastases
• ECOG: 2 - 5
• Age: <18 and >80
• Severe concomitant comorbidity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Perioperative XELOX chemotherapy; Oxaliplatin 130 mg/m2, d1 Capecitabine 1000 mg/m² two times per day (BID), d1-14, every 3 weeks (q3w) 4 cycles (12 weeks) pre-OP and 3 cycles (12 weeks) post-OP	Drug: Oxaliplatin; 85 mg/m², d1, i.v., every 2 weeks; Drug: Capecitabine; 1000 mg/m² two times per day (BID), d1-14; Drug: Oxaliplatin; 130 mg/m² d1 i.v. every 3 weeks; Other Names: oxaliplatine
Experimental: Perioperative FLOT chemotherapy; Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (8 weeks) pre-OP and 4 cycles (8 weeks) post-OP	Drug: Leucovorin; 200 mg/m², d1, i.v., every 2 weeks; Drug: Oxaliplatin; 85 mg/m², d1, i.v., every 2 weeks; Drug: Docetaxel; 50mg/m2, d1, i.v., every 2 weeks; Drug: Oxaliplatin; 130 mg/m² d1 i.v. every 3 weeks; Other Names: oxaliplatine; Drug: Fluorouracil; 2600 mg/m²d1 i.v. every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who complete all the treatment per protocol	Completed treatment protocol is considered as 4 cycles neoadjuvant chemotherapy followed by curative surgery and 4 cycles of adjuvant chemotherapy.	Up to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histopathological regression rate (Becker regression criteria)	To determine histopathological regression rate after FLOT regimen compared to XELOX regimen in neoadjuvant settings	2 weeks after surgery
Chemotherapy toxicity profile	To determine and compare toxicity profile in patients receiving XELOX or FLOT regimen	at the end of XELOX cycle (each cycle is 21 days) and FLOT cycle (each cycle is 14 days)
Surgical complications rate	To determine surgical complication rate and profile after different types of regimens in neoadjuvant settings	up to 90th day after surgery
1-year disease-free survival rate	To determine the efficacy of FLOT regimen compared to XELOX regimen during the first year after the surgery	1 year after surgery
Correlation between histopathological regression and disease-free survival	To determine correlation between histopathological regression and disease-free survival in different chemotherapeutic settings	2 years of follow-up after the last cycle of chemotherapy
Median overall survival	To determine the efficacy of FLOT regimen compared to XELOX regimen by assessment of overall survival	5 year follow up after the last cycle of chemotherapy

Collaborators and Investigators

• Sponsor: Ukrainian Society of Clinical Oncology
• Investigators: Principal Investigator: Oleksii Dobrzhanskyi, MD, National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2021
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 23, 2021
• First Posted (Actual): June 24, 2021

Study Record Updates

• Last Update Posted (Actual): November 6, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: gastric cancer; perioperative chemotherapy; gastrectomy; pathological responce rate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Docetaxel; Capecitabine; Oxaliplatin; Fluorouracil; Leucovorin
• Other Study ID Numbers: 275

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the initial publication every participant will recieve all the data to provide further data exploration.
• IPD Sharing Time Frame: Data will be available after initial paper is published.
• IPD Sharing Access Criteria: By request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No