Irinotecan-based Triplet (FOLFOXIRI) as Perioperative Treatment in Resectable Gastric and Gastroesophageal Junction Adenocarcinoma. (INTENSE)

In this clinical trial, patients with gastric and gastroesophageal junction adenocarcinoma will be included. Treatment with curative intent will be given with chemotherapy for 4 cycles with fluorouracil, oxaliplatin and irinotecan preoperatively followed by surgery, and then additionally 4 cycles of the same chemotherapy postoperatively. The standard treatment today is preoperative treatment with fluorouracil and oxaliplatin pre-and postoperatively. The rationale for this trial is, that the addition of irinotecan might improve treatments results.

Study Overview

• Status: Active, not recruiting
• Conditions: Resectable Gastric and Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Borg, MD; Phone Number: +46 46 17 75 20; Email: david.borg@skane.se
• Study Contact Backup: Name: Jan Sundberg, RN; Phone Number: +464617 70 34; Email: jan.sundberg@skane.se

Study Locations

• Norway
  • Oslo, Norway, 0450
    • Oslo University Hospital, Ullevål hospital
• Sweden
  • Lund, Sweden, 221 85
    • Lund University Hospital
  • Stockholm, Sweden, 141 86
    • Karolinska University Hospital
  • Växjö, Sweden, 352 34
    • Centrallasarettet i Växjö

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically verified, resectable gastric or gastroesophageal (GE) (gastroesophageal) junction (Siewert type I-III) adenocarcinoma Confirmation of patient operability by surgeon
• Primary tumor, regional nodes, metastasis (TNM), 8th edition): cT2-4a or cN+, cM0
• Age: 18 years or older
• World Health Organization (WHO) performance status ≤ 1
• Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy

• Adequate laboratory findings:

  • hematological: hemoglobin > 90 g/L (transfusion is allowed to attain this), absolute neutrophil count (ANC) ≥ 1,5 x 109/L, platelets ≥ 75 x 109/L
  • hepatic: bilirubin ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALAT) ≤ 3 x ULN
  • renal: creatinine ≤ 1.5 x ULN (upper limit of normal)

• Fertile men and women must use highly effective means of contraception (failure rate <1%) such as:

  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal administration)
  • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable administration)
  • intrauterine device
  • intrauterine hormone-releasing system
  • bilateral tubal occlusion
  • vasectomised partner
  • sexual abstinence
• Signed written informed consent
• The patient must be able to comply with the protocol

Exclusion Criteria:

• Neuroendocrine or adenosquamous carcinoma
• Prior oncological treatment or surgical resection for the present disease
• Presence of other concurrent malignancies or previous malignancies within 5 years except for adequately treated basal or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix uteri
• Clinically significant (i.e. active) cardiovascular disease e.g. myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade III-IV congestive heart failure
• Active inflammatory bowel disease
• Symptomatic peripheral neuropathy greater than grade 1 (CTCAE version 4.03)
• Known hypersensitivity to any contents of the study drugs
• Pregnancy (positive pregnancy test) and/or breast feeding
• Any other serious or uncontrolled illness which in the opinion of the investigator makes it undesirable for the patient to enter the trial

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: Treatment with chemotherapy pre- and postoperative.

Drug: Fluorouracil; Treatment with Fluorouracil, Oxaliplatin, and Irinotecan is given for 4 cycles pre- and postoperatively, in total 8 cycles.; Drug: Oxaliplatin; Treatment with Fluorouracil, Oxaliplatin, and Irinotecan is given for 4 cycles pre- and postoperatively, in total 8 cycles.; Drug: Irinotecan; Treatment with Fluorouracil, Oxaliplatin, and Irinotecan is given for 4 cycles pre- and postoperatively, in total 8 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the rate of histopathological response according to Becker criteria.	Assessment of histopathological response, ypTNM, resection margin and residual tumor status. If Laurén classification and mismatch repair (MMR) or microsatelite instability status (MSI) could not be assessed on pretreatment biopsies it should be assessed on the resected specimen. Results do not have to be awaited before start of chemotherapy.	After surgery.

Collaborators and Investigators

• Sponsor: Lund University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: December 10, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Fluorouracil; Chemotherapy; Irinotecan; Gastric adenocarcinoma; Gastroesophageal junction adenocarcinoma; Oxaliplatin; Histopathological response; Preoperative chemotherapy; Postoperative chemotherapy; Rate of R0-resection
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Oxaliplatin; Irinotecan
• Other Study ID Numbers: SEGCG18-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No