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Use of Cetuximab for Unresectable or Metastatic Esophageal and Gastric Cancer

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00130689
First received: August 15, 2005
Last updated: May 12, 2015
Last verified: May 2015

August 15, 2005
May 12, 2015
July 2005
September 2010   (final data collection date for primary outcome measure)
Overall Response Rate [ Time Frame: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 weeks (range 1-23 weeks). ] [ Designated as safety issue: No ]
Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
To assess the response rate of cetuximab in patients with advanced esophageal or gastric cancer that has not responded to 1-2 prior chemotherapy regimens given in the metastatic setting.
Complete list of historical versions of study NCT00130689 on ClinicalTrials.gov Archive Site
Not Provided
  • To evaluate the duration of response, progression-free survival and overall survival of patients with advanced or metastatic esophageal or gastric cancer treated with cetuximab
  • to assess the safety of cetuximab
Not Provided
Not Provided
 
Use of Cetuximab for Unresectable or Metastatic Esophageal and Gastric Cancer
A Phase II Trial of Cetuximab in Unresectable or Metastatic Esophageal and Gastric Carcinoma
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.

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%.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Esophageal Cancer
  • Gastric Cancer
  • Neoplasm Metastasis
Drug: Cetuximab
Other Name: erbitux
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.
Intervention: Drug: Cetuximab
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):1367-73. doi: 10.1093/annonc/mdq604.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
43
September 2010
September 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00130689
05-113
Yes
Not Provided
Not Provided
Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
  • Bristol-Myers Squibb
  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
Principal Investigator: Jennifer A. Chan, MD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP