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

Gastric Cancer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01360086
• Other study ID #: CDR0000699219
• Secondary ID: FFCD-0901EU-2111
• Status: Completed
• Phase: Phase 2
• First received: May 20, 2011
• Last updated: May 27, 2016
• Start date: June 2011
• Est. completion date: March 2013

Study information

• Verified date: May 2016
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Esophageal Neoplasms
• Gastric Cancer
• Stomach Neoplasms

Intervention

Biological:
• cetuximab
6 cycles of intravenous Cetuximab (500mg/m²),

Drug:
• cisplatin
Cisplatine (50mg/m²)
• fluorouracil
LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks
• leucovorin calcium

Procedure:
• adjuvant therapy

• neoadjuvant therapy

• quality-of-life assessment

• therapeutic conventional surgery
Surgery was planned 3-4 weeks after the end of neaodjuvant CT

Locations

Country	Name	City	State
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	CHU - Robert Debre	Reims

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

References & Publications (1)

Mariette C, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Robb WB, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal can — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate according to RECIST V1.1 criteria		3 months	No
Primary	Non-toxicity rate		3 months	Yes
Secondary	Tolerance		From Inclusion	Yes
Secondary	Post-operative mortality and morbidity		After Surgery	Yes
Secondary	Rate of recurrence at 1 and 2 years		1 year and 2 years	No
Secondary	Recurrence-free survival at 3 years		3 years	No
Secondary	Disease-free survival at 3 years		3 years	No
Secondary	Overall survival at 3 years		3 years	No
Secondary	Quality of life as assessed by QLC-C30 and STO-22 questionnaires		From inclusion	No