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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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00397904
First received: November 9, 2006
Last updated: March 8, 2013
Last verified: March 2013

November 9, 2006
March 8, 2013
October 2006
September 2010   (final data collection date for primary outcome measure)
Complete and partial response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete and partial response rate
Complete list of historical versions of study NCT00397904 on ClinicalTrials.gov Archive Site
  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Progression-free survival
  • Overall survival
  • Toxicity
Not Provided
Not Provided
 
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
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Esophageal Cancer
  • Gastric Cancer
  • Biological: cetuximab
  • Drug: cisplatin
  • Drug: irinotecan hydrochloride
  • Other: immunohistochemistry staining method
  • Other: laboratory biomarker analysis
  • Procedure: biopsy
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.
Interventions:
  • Biological: cetuximab
  • Drug: cisplatin
  • Drug: irinotecan hydrochloride
  • Other: immunohistochemistry staining method
  • Other: laboratory biomarker analysis
  • Procedure: biopsy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
September 2010
September 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00397904
06-095, P30CA008748, MSKCC-06095
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Principal Investigator: David H. Ilson, MD, PhD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
March 2013

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