A Study of Cetuximab(Erbitux) With Cisplatin and Capecitabine(Xeloda)as 1st Line Treatment in the Advanced Gastric Cancer (EXTRA)

The purpose of this study is to investigate whether cetuximab (Erbitux®) with cisplatin and capecitabine (Xeloda) as 1st line treatment in the advanced gastric cancer is effective.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: cetuximab, cisplatin, capecitabine

Detailed Description

Gastric cancer remains one of the major causes of cancer deaths around the world, especially in Asia. Previous study of ML17032 has proved that XP(capecitabine plus cisplatin)is effective in advanced gastric cancer, with the overall response rate of 41%, the median PFS of 5.6 month. Recently, the EGFR monoclonal antibody of cetuximab has shown to be successful in treating advanced colorectal cancer with or without chemotherapy. Since EGFR also express in gastric cancer, A single arm, open, multicenter phase II study of cetuximab in combination with cisplatin and capecitabine as first line treatment in patient with advanced gastric cancer.If applicable, the value of mutations in k-ras, b-raf, P53, and EGFR copy number to predict the clinical response to cetuximab in advanced gastric cancer patients will also be accessed.Tumor tissue from study patients will be checked for k-ras, b-raf, and P53 mutation by sequencing and for EGFR copy number by chromogenic in situ hybridization. DNA will be extracted from paraffin-embedded samples.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100036
    • Peking University,School of Oncology, Gastrointestinal Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Having signed informed consent
• Age 18 to 75 years old
• Histologically confirmed gastric adenocarcinoma
• Unresectable recurrent or metastatic disease
• Previous neo-adjuvant or adjuvant treatment for gastric cancer, if applicable, more than 12 months
• Measurable disease according to the RECIST criteria
• Karnofsky performance status ≥60
• Life expectancy of ≥2 month
• No prior radiotherapy except radiotherapy at non-target lesion of the study more than 4 weeks
• ALT and AST<2.5 times ULN (≤5 times ULN in patients with liver metastases)
• Serum albumin level ≥3.0g/dL
• Serum AKP < 2.5 times ULN
• Serum creatinine <1.5mg/dL
• Bilirubin level < 1.5mg/dL
• Serum creatinine <1.5 times ULN
• WBC>3,000/mm3, absolute neutrophil count ≥2000/mm3, platelet>100,000/mm3, Hb>9g/dl

Exclusion Criteria:

• Brain metastasis (known or suspected)
• Previous systemic therapy for metastatic gastric cancer
• Inability to take oral medication
• Previous EGFR pathway-targeting therapy
• Surgery (excluding diagnostic biopsy) within 4 weeks prior to study entry
• Heart failure, coronary artery disease, myocardial infarction within the last 6 months
• Known allergy to any study treatment
• Pregnancy or lactation period
• Any investigational agent within the past 28 days
• Other previous malignancy within 5 year, except non-melanoma skin cancer
• Previous adjuvant therapy with capecitabine+platinum
• Pre-existing neuropathy>grade 1
• Legal incapacity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: C225+Chemotherapy

Drug: cetuximab, cisplatin, capecitabine; Product 1: Cetuximab(Erbitux®) Dosing schedule: 400mg/m2 initial dose and then 250mg/m2 ,weekly dose Mode of administration: intravenously Product 2: capecitabine Dosing schedule: 1000mg/m2 bid, days 1-14, every 3 weeks Mode of administration: orally Product 3: cisplatin Dosing schedule: 80mg/m2, day 1 of every 3 weeks Mode of administration: intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tumor response rate	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to progression Disease control rate Overall survival K-ras, b-raf, p53 gene mutation and EGFR gene copy number vs. tumor response safety	5 year

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Lin Shen, MD, Peking University, School of oncology, Gastrointestinal Department

Publications and helpful links

General Publications

• Zhang X, Xu J, Liu H, Yang L, Liang J, Xu N, Bai Y, Wang J, Shen L. Predictive biomarkers for the efficacy of cetuximab combined with cisplatin and capecitabine in advanced gastric or esophagogastric junction adenocarcinoma: a prospective multicenter phase 2 trial. Med Oncol. 2014 Oct;31(10):226. doi: 10.1007/s12032-014-0226-y. Epub 2014 Sep 19.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): February 1, 2009

Study Registration Dates

• First Submitted: May 22, 2007
• First Submitted That Met QC Criteria: May 22, 2007
• First Posted (ESTIMATE): May 24, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): May 19, 2015
• Last Update Submitted That Met QC Criteria: May 17, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: cisplatin; capecitabine; Cetuximab; first line treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cisplatin; Capecitabine; Cetuximab
• Other Study ID Numbers: EMR 62202-769