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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00397904
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 47
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer; Gastric Cancer	Biological: cetuximab; Drug: cisplatin; Drug: irinotecan hydrochloride; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: biopsy	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Cetuximab Plus Cisplatin and Irinotecan in Patients With Irinotecan and Cisplatin-Refractory Metastatic Esophageal and Gastric Cancer
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

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.

Biological: cetuximab; Drug: cisplatin; Drug: irinotecan hydrochloride; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Procedure: biopsy

Outcome Measures

Primary Outcome Measures

1. Complete and Partial Response Rate [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00397904
• Other Study ID Numbers: 06-095; P30CA008748; MSKCC-06095
• First Posted: Nov 10, 2006
• Last Update Posted: Nov 25, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: 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
• Additional relevant MeSH terms: Stomach Neoplasms; Esophageal Neoplasms; Irinotecan; Cetuximab

Study Results

Participant Flow

Arm/Group Title	Cetuximab, Cisplatin, and Irinotecan
Arm/Group Description	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.
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Cetuximab, Cisplatin, and Irinotecan
Arm/Group Description	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.
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 75%
>=65 years	4 25%
Sex: Female, Male (Count of Participants)
Female	4 25%
Male	12 75%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Complete and Partial Response Rate
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cetuximab, Cisplatin, and Irinotecan
Arm/Group Description	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.
Measure Participants	16
Complete Response	0 0%
Partial Response	1 6.3%
Stable Disease	4 25%
Progression of Disease	11 68.8%

Adverse Events

Arm/Group Title	Cetuximab, Cisplatin, and Irinotecan
Arm/Group Description	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.
All Cause Mortality
	Cetuximab, Cisplatin, and Irinotecan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Cetuximab, Cisplatin, and Irinotecan
	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/16 (6.3%)	1
Anemia	2/16 (12.5%)	2
Gastrointestinal disorders
Diarrhea	1/16 (6.3%)	1
Mucositis oral	1/16 (6.3%)	1
Nausea	1/16 (6.3%)	1
Vomiting	1/16 (6.3%)	1
General disorders
Sudden death NOS	1/16 (6.3%)	1
Death-Disease Progression NOS	1/16 (6.3%)	1
Investigations
Blood bilirubin increased	1/16 (6.3%)	1
Cardiac troponin I increased	1/16 (6.3%)	1
Platelet count decreased	1/16 (6.3%)	1
Metabolism and nutrition disorders
Hypocalcemia	1/16 (6.3%)	1
Dehydration	1/16 (6.3%)	1
Hyperglycemia	1/16 (6.3%)	1
Hypokalemia	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Myositis	1/16 (6.3%)	1
Vascular disorders
Thrombosis	2/16 (12.5%)	2
Other (Not Including Serious) Adverse Events
	Cetuximab, Cisplatin, and Irinotecan
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Anemia	7/16 (43.8%)	34
Gastrointestinal disorders
Constipation	1/16 (6.3%)	1
Diarrhea	1/16 (6.3%)	1
Dysphagia	1/16 (6.3%)	1
Vomiting	1/16 (6.3%)	1
General disorders
Fatigue	6/16 (37.5%)	6
Investigations
Alkaline phosphatase increase	3/16 (18.8%)	10
Cardiac troponin I increased	1/16 (6.3%)	1
INR increased	2/16 (12.5%)	10
White blood cell decreased	3/16 (18.8%)	5
Lymphocyte count decreased	7/16 (43.8%)	13
Neutrophil count decreased	2/16 (12.5%)	3
Weight loss	1/16 (6.3%)	1
Metabolism and nutrition disorders
Hypoalbuminemia	6/16 (37.5%)	22
Hyperglycemia	4/16 (25%)	12
Hypomagnesemia	6/16 (37.5%)	32
Hypophosphatemia	1/16 (6.3%)	6
Hyperkalemia	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/16 (6.3%)	2
Skin and subcutaneous tissue disorders
Alopecia	1/16 (6.3%)	1
Rash: acne/acneiform	4/16 (25%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.