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

Phase 2

Completed

• Conditions: Adenocarcinoma of the Gastroesophageal Junction; Gastric Cancer
• Interventions: Biological: cetuximab; Drug: cisplatin; Drug: fluorouracil; Drug: leucovorin calcium; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Procedure: quality-of-life assessment; Procedure: therapeutic conventional surgery

• Registration Number: NCT01360086
• Lead Sponsor: Federation Francophone de Cancerologie Digestive

Brief Summary

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.

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 Timeline

• Study First Submitted: 2011-05-20
• Study First Submitted QC: 2011-05-20
• Study First Posted: 2011-05-25
• Study Start: 2011-06
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-27
• Last Update Posted: 2016-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Perioperative CT with 5FU-Cisplatine-Cetuximab	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.
Perioperative CT with 5FU-Cisplatine-Cetuximab	leucovorin calcium	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.
Perioperative CT with 5FU-Cisplatine-Cetuximab	adjuvant therapy	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.
Perioperative CT with 5FU-Cisplatine-Cetuximab	neoadjuvant therapy	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.
Perioperative CT with 5FU-Cisplatine-Cetuximab	quality-of-life assessment	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.
Perioperative CT with 5FU-Cisplatine-Cetuximab	therapeutic conventional surgery	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.
Perioperative CT with 5FU-Cisplatine-Cetuximab	fluorouracil	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.
Perioperative CT with 5FU-Cisplatine-Cetuximab	cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Objective response rate according to RECIST V1.1 criteria	3 months
Non-toxicity rate	3 months

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Centre Hospitalier Regional et Universitaire de Lille; 🇫🇷 Lille, France

CHU - Robert Debre; 🇫🇷 Reims, France