Cetuximab, Cisplatin, and Irinotecan in Treating Patients With Metastatic Esophageal Cancer, Gastroesophageal Junction Cancer, or Gastric Cancer That Did Not Respond to Previous Irinotecan and Cisplatin

October 22, 2015 updated by: Memorial Sloan Kettering Cancer Center

Phase II Trial of Cetuximab Plus Cisplatin and Irinotecan in Patients With Irinotecan and Cisplatin-Refractory Metastatic Esophageal and Gastric Cancer

RATIONALE: 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. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Drugs used in chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with cisplatin and irinotecan may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin and irinotecan works in treating patients with metastatic esophageal cancer, gastroesophageal junction cancer, or gastric cancer that did not respond to previous irinotecan and cisplatin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the response rate in patients with irinotecan hydrochloride- and cisplatin-refractory metastatic esophageal, gastroesophageal junction, or gastric cancer treated with cetuximab, cisplatin, and irinotecan hydrochloride.

Secondary

  • Determine the median survival of patients treated with this regimen.
  • Determine the tolerability of this regimen in these patients.
  • Determine the adverse event profiles in patients treated with this regimen.
  • Assess epidermal growth factor receptor expression in tumor tissue from patients treated with this regimen.

OUTLINE: This is an open-label, nonrandomized study.

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and cisplatin IV over 30 minutes and irinotecan hydrochloride IV over 30-90 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor biopsy at baseline to evaluate epidermal growth factor receptor by immunohistochemistry.

After completion of study treatment, patients are followed every 3 months for up to 1 year.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diagnosis of 1 of the following:

    • Adenocarcinoma or squamous cell carcinoma of the esophagus
    • Adenocarcinoma of the gastroesophageal junction
    • Adenocarcinoma of the stomach
  • Metastatic disease
  • Measurable disease by diagnostic CT scan or MRI

  • Failed prior treatment with cisplatin and irinotecan hydrochloride, defined by the following:

    • Radiographic progression within 12 weeks* from the last dose of prior cisplatin and irinotecan hydrochloride, administered either as adjuvant or neoadjuvant therapy, OR as therapy for metastatic disease NOTE: *Prior irinotecan hydrochloride and cisplatin must have been administered within the past 12 weeks; other chemotherapy regimens may have been administered between the time of disease progression or prior irinotecan hydrochloride/cisplatin and study entry

  • Pathologic tissue available for immunohistochemistry (IHC) staining for the epidermal growth factor receptor (EGFR)

    • Positive or negative EGFR by IHC allowed

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • Life expectancy > 3 months
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin normal
  • AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
  • Creatinine ≤ 2.0 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior severe infusion reaction to a monoclonal antibody
  • No history of allergic reactions to compounds of similar chemical or biologic composition to irinotecan hydrochloride, cisplatin, or other study agents
  • No prior intolerance to irinotecan hydrochloride or cisplatin despite prior dose attenuations

  • No uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection requiring parenteral antibiotics
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Uncontrolled hypertension
    • Clinically significant cardiac arrhythmia
    • Myocardial infarction within the past 6 months
    • HIV infection
    • Psychiatric illness or social situations that would preclude study compliance
  • No history of Gilbert's disease
  • No medical condition or reason that would preclude study treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 3 weeks since prior chemotherapy or radiotherapy and recovered
  • No more than 2 prior treatment regimens for metastatic disease
  • No prior therapy specifically and directly targeting the epidermal growth factor receptor pathway

  • No prior anticancer murine or chimeric monoclonal antibody therapy

    • Prior humanized monoclonal antibody therapy allowed
  • No concurrent antiseizure medications known to affect the metabolism of irinotecan hydrochloride, including phenytoin or phenobarbital
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cetuximab, Cisplatin, and Irinotecan
Cetuximab will be combined with weekly irinotecan and cisplatin. Patients will receive cetuximab 400 mg/m2 on day 1, week 1. Following this loading dose, patients will receive weekly cetuximab 250 mg/m2 (day 8, 15, 22, etc.) until disease progression or unacceptable toxicity. Patients will continue to receive irinotecan and cisplatin weekly on day 1 and day 8, on an every 21 day cycle. The standard maximum doses are irinotecan 65 mg/m2 and cisplatin 30 mg/m2.
Drug: irinotecan hydrochloride
Other: laboratory biomarker analysis
Procedure: biopsy
Drug: cisplatin
Other: immunohistochemistry staining method
Biological: cetuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete and Partial Response Rate
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

November 9, 2006

First Submitted That Met QC Criteria

November 9, 2006

First Posted (Estimate)

November 10, 2006

Study Record Updates

Last Update Posted (Estimate)

November 25, 2015

Last Update Submitted That Met QC Criteria

October 22, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-095
  • P30CA008748 (U.S. NIH Grant/Contract)
  • MSKCC-06095

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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