Use of Cetuximab for Unresectable or Metastatic Esophageal and Gastric Cancer

NCT ID: NCT00130689

Last Updated: 2015-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2010-09-30

Brief Summary

Purpose: There remains a great need for novel therapeutic agents and treatment strategies for advanced esophagogastric cancer. Preclinical and clinical studies have demonstrated increased EGFR expression in a significant proportion of both esophageal and gastric carcinomas. Inactivation of EGFR through use of a monoclonal antibody in preclinical models has resulted in inhibition of tumor growth. Agents designed to block the EGFR pathway have demonstrated disease control among previously treated patients with metastatic esophageal and gastric cancer. The proposed mechanism of action for cetuximab is its ability to effectively disrupt EGFR-mediated signal transduction pathways that ultimately leads to halting cell cycle progression, induces apoptosis, and also inhibits processes important for tumor growth, such as cell invasion and angiogenesis.

Detailed Description

OBJECTIVES:

Primary - To assess the response rate of single-agent cetuximab in patients with advanced esophageal or gastric cancer who have failed 1-2 prior chemotherapy regimens given in the metastatic setting.

Secondary

• To evaluate the duration of response, progression-free survival and overall survival.
• To assess the safety of cetuximab.

Exploratory

• To assess whether levels of EGFR expression and/or EGFR mutation status correlates with response and toxicity of cetuximab.

STATISTICAL DESIGN:

This study used a two-stage design to evaluate efficacy of cetuximab based on overall response (OR) defined as complete response (CR) or partial response (PR). The null and alternative OR rate were 5% and 15%. If one or more patients enrolled in the stage one cohort (n=20 patients) achieved PR or better than accrual would proceed to stage two (n=16 patients). There was 36% probability of stopping the trial at stage one if the true OR rate was 5%. The probability that the regimen would be considered promising if the true OR rate was 5% was 10% and 80% if the true OR rate was 15%.

Conditions

Esophageal Cancer; Gastric Cancer; Neoplasm Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab

Patients received cetuximab at an initial dose of 400 mg/m2 administered IV over 120 min, followed by weekly infusions at 250 mg/m2 administered IV over 60 min. Once cycle was 4 weeks of therapy. Patients received treatment until disease progression or unacceptable toxicity.

Group Type: OTHER

Cetuximab

Intervention Type: DRUG

Interventions

Cetuximab

Intervention Type: DRUG

Other Intervention Names

erbitux

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed, unresectable or metastatic stage IV esophageal or gastric adenocarcinoma. Tumors with squamous cell differentiation, including those with a mixture of squamous and adenomatous differentiation, are excluded.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT) scan or greater than or equal to 2 cm by other radiographic technique. Disease in an irradiated field as only site of measurable disease is acceptable if there has been a clear progression of the lesion.
• Patients must have at least one paraffin block or twenty unstained slides available for analysis of epidermal growth factor receptor (EGFR) status.
• Treatment with 1-2 prior chemotherapy regimens given in the metastatic setting for unresectable or metastatic esophageal or gastric carcinoma.
• ECOG performance status 0-2.
• Life expectancy greater or equal to 12 weeks.
• Age 18 years or older.
• Ability to sign an informed consent document.
• Neutrophils greater than or equal to 1,000/mm3.
• Platelets greater than or equal to 75,000/mm3.
• Serum bilirubin less than or equal to 2.0 mg/dl.
• Serum creatinine less than or equal to 1.5 mg/dl.
• Aspartate aminotransferase (AST or SGOT) less than or equal to 2.5 x upper institutional normal limit.

Exclusion Criteria

• Pregnant or lactating women. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of initiation of therapy. Men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while in this study.
• Subjects should have no other active malignancy other than non-melanoma skin cancer or in-situ cervical carcinoma. A resected cancer (other than in-situ carcinoma) must have demonstrated no evidence of recurrence for at least 3 years.
• Subjects should not have a significant history of cardiac disease, i.e., uncontrolled hypertension; unstable angina; congestive heart failure; myocardial infarction less than 6 months prior to registration; or serious uncontrolled cardiac arrhythmia.
• Subjects must not have received prior cetuximab or other therapy that specifically and directly targets the EGFR pathway. Prior therapy with bevacizumab is permissible.
• Subjects must not have experienced prior severe infusion reaction to a monoclonal antibody.
• Subjects must not have received any chemotherapy regimen or radiation therapy within 28 days prior to study entry.
• Patients must have completed any major surgery 4 weeks or any minor surgery 2 weeks prior to the first infusion of cetuximab. Patients must have fully recovered from the procedure.
• No concurrent use of chemotherapy, radiation, or other investigational agents is allowed while participating in this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Jennifer Chan, MD, MPH

Overall PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer A. Chan, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

North Shore Medical Center Cancer Center

Peabody, Massachusetts, United States

Countries

United States

References

Chan JA, Blaszkowsky LS, Enzinger PC, Ryan DP, Abrams TA, Zhu AX, Temel JS, Schrag D, Bhargava P, Meyerhardt JA, Wolpin BM, Fidias P, Zheng H, Florio S, Regan E, Fuchs CS. A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol. 2011 Jun;22(6):1367-1373. doi: 10.1093/annonc/mdq604. Epub 2011 Jan 7.

Reference Type: RESULT

PMID: 21217058 (View on PubMed)

Other Identifiers

05-113

Identifier Type: -

Identifier Source: org_study_id