Neoadjuvant FOLFIRINOX in the Treatment of Locally Advanced Gastric Cancer (FOLFIRINOX)

Phase II single-arm study designed to evaluate the efficacy and safety of preoperative chemotherapy with FOLFIRINOX regimen. The investigators will include 27 patients with resectable locally advanced gastric cancer. They will receive preoperative chemotherapy with FOLFIRINOX regimen by long-term catheter every 14 days for 8 cycles accounting for a total of 4 months of systemic treatment. In the period between 4 and 8 weeks of the last cycle, restaging tests will be performed and if there is no metastatic progression of disease, the patient will undergo surgical treatment with curative intention. The objective is to evaluate whether preoperative treatment with FOLFIRINOX regimen involving continuous infusion and bolus infusion of 5-fluoruracil, irinotecan bolus and oxaliplatin bolus is effective and safe in the neoadjuvant treatment of locally advanced gastric cancer.

The planned recruitment period is 48 months (4 years). There will be a total of 4 months of preoperative chemotherapy. In case of limiting toxicity or disease progression, chemotherapy will be suspended and patients may undergo resection of the primary neoplasia at the discretion of the surgical team of the institution. Patients will be followed for 5 years after entry of the last participant in the protocol for OS and PFS evaluation. The end of the study will occur when the last participant completes their last follow-up visit, which should occur no later than 60 months after enrollment in the study.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: FOLFIRINOX

• Study Type: Interventional
• Enrollment (Anticipated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tiago B. Castria, MD PhD; Phone Number: +551138934531; Email: tiagobiachi@yahoo.com.br

Study Locations

• Brazil
  • São Paulo, Brazil, 01246-000
    • Recruiting
    • Instituto do Cancer do Estado de Sao Paulo
    • Contact: Tiago Castria, MD PhD; Phone Number: +5511 3893-2000; Email: tiagobiachi@yahoo.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological diagnosis of gastric adenocarcinoma that is amenable to surgical resection at diagnosis, with locally advanced disease criteria for clinical evaluation (T3 tumors, T4 tumors and / or regional lymph node involvement).
• Absence of metastatic disease at a distance (computerized tomography, diagnostic laparoscopy and peritoneal lavage).
• Age 18-75 years.
• Clinical functionality by the ECOG scale between 0 and 1.
• Preserved renal function (creatinine clearance greater than 50 mL / min).
• Signature of Informed Consent Form

Exclusion Criteria:

• Active neoplasm of another primary site other than non-melanoma skin carcinoma.
• Lesions of the esophagogastric transition
• Unresectable lesions by computed tomography and / or diagnostic laparoscopy.
• Obstructive tumors (acute intestinal occlusion or subocclusion).
• Tumors with signs of significant or persistent bleeding.
• Carcinoma in situ.
• Different histological type of adenocarcinoma.
• Gastric stump tumors.
• Previous chemotherapeutic or radiotherapy treatment.
• Current pregnancy or breastfeeding.
• Total bilirubin above 1.5mg / dL.
• Hepatic transaminases greater than 1.5 times the upper limit of normality.
• Decompensated and / or symptomatic cardiomyopathy: congestive heart failure with functional class greater than 2 by the New York Heart Association; active coronary disease; uncontrolled cardiac arrhythmia; history of acute myocardial infarction in the last 6 months.
• Psychological, familial, social or even geographical condition that potentially hinders adherence to the study protocol and the pre-established follow-up.
• Current or previous psychiatric or neurological diagnosis that is decompensated, compromises the cognition, functionality or adherence to the proposed treatment.
• Other comorbidities that are decompensated at the time of treatment.
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FOLFIRINOX; Oxaliplatin 85mg/m2, Leucovorin 200mg/m2, Irinotecan 180mg/m2, 5-FU 400mg/m2 bolus followed by 2400mg/m2 continuous infusion.	Drug: FOLFIRINOX; Oxaliplatin 85mg/m2, Leucovorin 200mg/m2, Irinotecan 180mg/m2, 5-FU 400mg/m2 bolus followed by 2400mg/m2 continuous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR)	To evaluate the Pathologic Complete Response (pCR).	4-8 weeks after neoadjuvant chemotherapy complete

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	Evaluate Disease-free survival (DFS).	At 2, 3 and 5 years after preoperative treatment with FOLFIRINOX regimen.
Overall survival (OS)	Evaluate Overall survival (OS).	At 2, 3 and 5 years after preoperative treatment with FOLFIRINOX regimen.
R0-resection rate	Evaluate the R0 resection rate (absence of microscopic residual disease).	4-8 weeks after neoadjuvant chemotherapy complete
Rate of Treatment Completion	Evaluate the rate of completion of treatment (chemotherapy and surgical approach).	4-8 weeks after neoadjuvant chemotherapy complete
Rate of adverse events	Rate and description of adverse events	Through neoadjuvant chemotherapy (4 months)
Rate of Disease Progression	Evaluate the rate of disease progression.	Through neoadjuvant chemotherapy (4 months)

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2017
• Primary Completion (Anticipated): December 30, 2026
• Study Completion (Anticipated): December 30, 2026

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: January 30, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Gastric Cancer; FOLFIRINOX
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents; Folfirinox
• Other Study ID Numbers: 933/16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

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