Fluorouracil, Cisplatin, Leucovorin Calcium, and Cetuximab in Treating Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction

May 27, 2016 updated by: Federation Francophone de Cancerologie Digestive

Trial Evaluating the Efficacy and Tolerance of Perioperative Chemotherapy With 5FU-Cisplatin-Cetuximab in Adenocarcinomas of the Stomach and Gastroesophageal Junction. Phase II Single Arm, Multicenter.

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) together with cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these drugs after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects of giving fluorouracil, cisplatin, and leucovorin calcium together with cetuximab and to see how well they work in treating patients with adenocarcinoma of the stomach or gastroesophageal junction.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To evaluate the objective response rate according to RECIST V1.1 criteria in patients with adenocarcinoma of the stomach or gastroesophageal junction treated with neoadjuvant chemotherapy comprising fluorouracil, cisplatin, leucovorin calcium, and cetuximab followed by surgery and adjuvant chemotherapy.
  • To determine the non-toxicity rate in these patients.

Secondary

  • To determine the rate of macroscopically and microscopically complete surgical resection (R0).
  • To determine the overall tolerance in patients treated with this regimen.
  • To determine post-operative mortality and morbidity in these patients.
  • To determine the rate of recurrence at 1 and 2 years in these patients.
  • To determine recurrence-free survival at 3 years in these patients.
  • To determine disease-free survival at 3 years in these patients.
  • To determine overall survival at 3 years in these patients.
  • To determine quality of life using EORTC QLC-C30 and STO-22 questionnaires.
  • To determine the correlation between the response rate and the degree of skin toxicity.

OUTLINE: This is a multicenter study.

  • Neoadjuvant therapy and surgery: Patients receive leucovorin calcium IV over 2 hours, cisplatin IV, fluorouracil IV continuously over 46 hours, and cetuximab IV over 1-2 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks after completing neoadjuvant chemotherapy, patients undergo surgery.
  • Adjuvant therapy: Within 4-8 weeks after completing neoadjuvant chemotherapy, patients receive leucovorin calcium, cisplatin, fluorouracil, and cetuximab as in neoadjuvant therapy. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaires (QLC-C30 and STO-22) periodically. Blood and tissue samples are collected periodically for correlative and translational studies.

After completing study therapy, patients are followed up every 4 months for 2 years and then every 6 months for 1 year.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France, 59037
        • Centre Hospitalier Regional et Universitaire de Lille
      • Reims, France, 51092
        • CHU - Robert Debre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction

    • Stage IB, II, or III disease according to TNM classification OR type I, II, or III disease according to Siewert classification

      • TNM: T1N1-3, T2N0-3, T3N0-3, or T4N0-3 (no T1N0 or M1)
    • Disease considered operable with curative intent

  • No gastric scirrhous carcinoma (linitis plastica)

    • Forms with independent cells are not considered linitis
  • Measurable disease according to RECIST V1.1
  • No planned esophagectomy without thoracotomy in patients with adenocarcinoma of the gastroesophageal junction type I

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Polynuclear neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine clearance > 50 mL/min
  • Bilirubin < 1.5 times normal
  • Serum albumin > 30 g/L
  • Prothrombin time ≥ 80%
  • FEV1 > 1 L in case of thoracotomy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known cirrhosis

  • No other progressive condition that has not been stabilized including the following:

    • Hepatic failure
    • Renal failure
    • Respiratory failure
    • NYHA class III-IV congestive heart failure
    • Unstable angina
    • Myocardial infarction in the past 6 months
    • Significant arrhythmias in the past 12 months
  • No recent weight loss exceeding 15%
  • No interstitial pneumonia
  • No other malignant tumor within the past 5 years except for basal cell skin carcinoma or cancer in situ of the cervix
  • No psychological, familial, or geographical reasons that will preclude the patient being monitored regularly
  • No persons deprived of liberty or under guardianship (Disability Act)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy or radiotherapy for gastric cancer
  • No other concurrent anticancer treatment, immunotherapy, or hormone therapy
  • No prior abdominal or thoracic radiotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Perioperative CT with 5FU-Cisplatine-Cetuximab
6 cycles of intravenous Cetuximab (500mg/m²), Cisplatine (50mg/m²) and LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks. Surgery was planned 3-4 weeks after the end of neaodjuvant CT and postoperative CT, with the same regimen, planned for 6-8 weeks after surgery.
Drug: leucovorin calcium
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: quality-of-life assessment
Biological: cetuximab
6 cycles of intravenous Cetuximab (500mg/m²),
Drug: cisplatin
Cisplatine (50mg/m²)
Drug: fluorouracil
LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks
Procedure: therapeutic conventional surgery
Surgery was planned 3-4 weeks after the end of neaodjuvant CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective response rate according to RECIST V1.1 criteria
Time Frame: 3 months
3 months
Non-toxicity rate
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival at 3 years
Time Frame: 3 years
3 years
Overall survival at 3 years
Time Frame: 3 years
3 years
Tolerance
Time Frame: From Inclusion
From Inclusion
Post-operative mortality and morbidity
Time Frame: After Surgery
After Surgery
Rate of recurrence at 1 and 2 years
Time Frame: 1 year and 2 years
1 year and 2 years
Recurrence-free survival at 3 years
Time Frame: 3 years
3 years
Quality of life as assessed by QLC-C30 and STO-22 questionnaires
Time Frame: From inclusion
From inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federation Francophone de Cancerologie Digestive

Investigators

  • Principal Investigator: Christophe Mariette, MD, PhD, Centre Hospitalier Regional et Universitaire de Lille

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

May 20, 2011

First Submitted That Met QC Criteria

May 20, 2011

First Posted (Estimate)

May 25, 2011

Study Record Updates

Last Update Posted (Estimate)

May 30, 2016

Last Update Submitted That Met QC Criteria

May 27, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000699219
  • FFCD-0901
  • EU-21111
  • EUDRACT-2010-023115-33
  • MERCK-FFCD-0901

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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