Clinical trial NCT00397904: 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
Official title: Phase II Trial of Cetuximab Plus Cisplatin and Irinotecan in Patients With Irinotecan and Cisplatin-Refractory Metastatic Esophageal and Gastric Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
recurrent esophageal cancer
recurrent gastric cancer
adenocarcinoma of the stomach
stage IV esophageal cancer
stage IV gastric cancer
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-11-10
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete and Partial Response Rate
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David H. Ilson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: