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

Federation Francophone de Cancerologie Digestive

Status and phase

Completed

Phase 2

Conditions

Gastric Cancer

Adenocarcinoma of the Gastroesophageal Junction

Treatments

Procedure: therapeutic conventional surgery

Procedure: quality-of-life assessment

Drug: leucovorin calcium

Drug: cisplatin

Biological: cetuximab

Procedure: neoadjuvant therapy

Procedure: adjuvant therapy

Drug: fluorouracil

Study type

Interventional

Funder types

Other

Identifiers

NCT01360086

FFCD-0901

EUDRACT-2010-023115-33

CDR0000699219

MERCK-FFCD-0901

EU-21111

Details and patient eligibility

About

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.

Full 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.

Enrollment

65 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

65 participants in 1 patient group

Perioperative CT with 5FU-Cisplatine-Cetuximab

Experimental group

Description:

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.

Treatment: