Randomized Phase II Study of ECF-C, IC-C, or FOLFOX-C in Metastatic Esophageal and GE Junction Cancer
| City: |
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Elkton MD |
| State: |
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Maryland |
| Zip Code: |
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21921 |
| Conditions: |
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Esophageal Cancer |
| Purpose: |
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor
cells, either by killing the cells or by stopping them from dividing. 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. Giving more than one chemotherapy drug (combination chemotherapy)
together with cetuximab may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying three different combination chemotherapy
regimens to compare how well they work when given together with cetuximab in treating
patients with metastatic esophageal cancer or gastroesophageal junction cancer.
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| Study Summary: |
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OBJECTIVES:
Primary
- Compare the tumor response rate in patients with metastatic esophageal or
gastroesophageal junction cancer treated with epirubicin hydrochloride, cisplatin,
fluorouracil, and cetuximab (ECF-C); irinotecan hydrochloride, cisplatin, and cetuximab
(IC-C); or fluorouracil, oxaliplatin, leucovorin calcium, and cetuximab (FOLFOX-C).
Secondary
- Compare overall survival of patients treated with these regimens.
- Compare progression-free survival of patients treated with these regimens.
- Compare treatment failure in patients treated with these regimens.
- Determine the type and severity of toxicities associated with these regimens in the
multi-institutional phase II setting.
- Correlate quantitative immunohistochemistry results with objective response rate,
overall survival, and time to progression in these patients.
- Evaluate the cellular damage (i.e., apoptosis) as a result of oxaliplatin in these
patients.
- Determine if germline epidermal growth factor receptor (EGFR) variants correlate with
skin rash in patients treated with cetuximab.
- Correlate germline EGFR variants with tumor EGFR expression as measured by
immunohistochemistry.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
histology (squamous cell carcinoma vs adenocarcinoma) and ECOG performance status (0 or 1 vs
2). Patients are randomized to 1 of 3 treatment arms.
- Arm I (ECF + cetuximab): Patients receive cetuximab IV over 1-2 hours on days 1, 8, and
15; epirubicin hydrochloride IV followed by cisplatin IV over 1 hour on day 1; and
fluorouracil IV continuously on days 1-21. Treatment repeats every 21 days in the
absence of disease progression and unacceptable toxicity.
- Arm II (IC + cetuximab): Patients receive cetuximab IV over 1-2 hours on days 1, 8, and
15 and cisplatin IV over 30 minutes followed by irinotecan hydrochloride IV over 90
minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease
progression or unacceptable toxicity.
- ARM III (FOLFOX + cetuximab): Patients receive cetuximab IV over 1-2 hours on days 1
and 8; oxaliplatin IV over 2 hours followed by leucovorin calcium IV over 2 hours on
day 1; and fluorouracil IV continuously over 46-48 hours on days 1 and 2. Treatment
repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor sample collection at baseline to examine quantitative
immunofluorescence with subcellular localization for epidermal growth factor receptor
(EGFR), phospho EGFR, HER-2, phospho-HER-2, HER-3, HER-4, FEF, AKT, phospho AKT, PTEN,
gastrin-releasing peptide (GRP), and GRP receptor levels. Tumor samples are collected at
baseline from patients randomized to arm III to evaluate molecular mechanisms for
correlative studies. Cellular damage (i.e., apoptosis) by oxaliplatin is determined by DNA
fragmentation by TUNEL assay.
After completion of study treatment, patients are followed periodically for up to 2 years.
PROJECTED ACCRUAL: A total of 270 patients will be accrued for this study.
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| Criteria: |
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DISEASE CHARACTERISTICS:
- Histologically, cytologically, or radiologically confirmed esophageal cancer,
including any of the following types:
- Squamous cell carcinoma
- Adenocarcinoma* of the esophagus
- Adenocarcinoma* of the gastroesophageal (GE) junction according to Siewert
classification
- Type I or II disease
- No type III disease NOTE: Undifferentiated adenocarcinoma and
adenosquamous tumor will be considered as adenocarcinoma
- Metastatic disease or locally recurrent or residual (post-resection) disease
- Resected esophageal or GE junction disease that develops radiological or
clinical evidence of metastatic disease does not require histological or
cytological confirmation of metastatic disease unless 1 of the following is
true:
- More than 5 years since primary surgery and development of metastatic
disease
- Primary cancer was stage I
- Measurable disease, defined as at least 1 unidimensionally measurable lesion (longest
diameter) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- Must have ≥ 1 paraffin block (or ≥ 15 unstained slides) available for analysis of
tumor epidermal growth factor receptor (EGFR) status
- No known CNS metastases or carcinomatous meningitis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Platelet count ≥ 100,000/mm^3
- Granulocyte count ≥ 1,500/mm^3
- Creatinine ≤ 1.5 mg/dL
- AST ≤ 5.0 times upper limit of normal
- Bilirubin ≤ 1.5 mg/dL
- Albumin ≥ 2.5 g/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Must have a stable weight loss of (i.e., < 1 pound weight loss during the past week)
- No diarrhea ≥ grade 2 within the past 7 days
- No myocardial infarction within the past 6 months
- No New York Heart Association class III or IV congestive heart failure
- No interstitial pneumonia or symptomatic interstitial fibrosis of the lung
- No seizure disorder or active neurological disease requiring anti-epileptic
medication
- No peripheral neuropathy ≥ grade 2
- No evidence of Gilbert's syndrome
- No prior allergic reaction to chimerized or murine monoclonal antibody therapy or
documented presence of human anti-mouse antibodies (HAMA)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy or radiotherapy
- No prior therapy that specifically and directly targets the EGFR pathway
- At least 4 weeks since prior major surgery* and recovered
- At least 2 weeks since prior minor surgery* and recovered
- No concurrent palliative radiotherapy
- No other concurrent investigational agent
- No other concurrent chemotherapy
- No concurrent hormonal therapy except for the following:
- Steroids given temporarily for adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)
- Intermittent steroids (e.g., dexamethasone) as an antiemetic NOTE: *Insertion of
a vascular device is not considered major or minor surgery
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| NCT ID: |
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NCT00381706 |
| Primary Contact: |
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Study Chair
Peter C. Enzinger, MD
Dana-Farber Cancer Institute
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| Backup Contact: |
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N/A |
| Location Contact: |
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Elkton MD, Maryland 21921
United States
Stephen S. Grubbs, MD
Phone: 302-366-1200
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 21, 2013 |
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