Fluorouracil, Cisplatin, Leucovorin Calcium, and Cetuximab in Treating Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction
Condition: Adenocarcinoma of the Gastroesophageal Junction; Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): cetuximab; cisplatin; fluorouracil; leucovorin calcium; adjuvant therapy; neoadjuvant therapy; quality-of-life assessment; therapeutic conventional surgery
Intervention type(s): Biological; Drug; Drug; Drug; Procedure; Procedure; Procedure; Procedure
Intervention description(s): 6 cycles of intravenous Cetuximab (500mg/m²),; Cisplatine (50mg/m²); 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
Intervention MeSH terms: Leucovorin; Fluorouracil; Cetuximab; Calcium; Levoleucovorin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the gastroesophageal junction; adenocarcinoma of the stomach; stage IB gastric cancer; stage IIA gastric cancer; stage IIB gastric cancer; stage IIIA gastric cancer; stage IIIB gastric cancer; stage IIIC gastric cancer