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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA008748 | U.S. NIH Grant/Contract | View source | |
| MSKCC-06095 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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
Secondary
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cetuximab, Cisplatin, and Irinotecan | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cetuximab | Biological |
| ||
| cisplatin |
| Measure | Description | Time Frame |
|---|---|---|
| Complete and Partial Response Rate | 2 years |
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DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed diagnosis of 1 of the following:
Metastatic disease
Measurable disease by diagnostic CT scan or MRI
Failed prior treatment with cisplatin and irinotecan hydrochloride, defined by the following:
Pathologic tissue available for immunohistochemistry (IHC) staining for the epidermal growth factor receptor (EGFR)
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:
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
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
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| Name | Affiliation | Role |
|---|---|---|
| David H. Ilson, MD, PhD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10065 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| irinotecan hydrochloride | Drug |
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| immunohistochemistry staining method | Other |
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| laboratory biomarker analysis | Other |
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| biopsy | Procedure |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Complete and Partial Response Rate | Posted | Number | participants | 2 years |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 7 | 16 | 16 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood bilirubin increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Cardiac troponin I increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Sudden death NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Death-Disease Progression NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Alkaline phosphatase increase | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Cardiac troponin I increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| INR increased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| White blood cell decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Neutrophil count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Weight loss | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. David Ilson | Memorial Sloan Kettering Cancer Center | 646-888-4183 | ilsond@mskcc.org |
| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| D013274 | Stomach Neoplasms |
| C562730 | Adenocarcinoma Of Esophagus |
| D000077277 | Esophageal Squamous Cell Carcinoma |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D018307 | Neoplasms, Squamous Cell |
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| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| D002945 | Cisplatin |
| D000077146 | Irinotecan |
| D007150 | Immunohistochemistry |
| D001706 | Biopsy |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006651 | Histocytochemistry |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D006652 | Histological Techniques |
| D008919 | Investigative Techniques |
| D007158 | Immunologic Techniques |
| D003581 | Cytodiagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
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| Title | Measurements |
|---|---|
|
| Progression of Disease |
|