|Phase II||Treatment||Active||18 and over||NCI, Other||CDR0000515093|
RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, fluorouracil, and leucovorin, 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 bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) together with bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with recurrent, unresectable, or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal cancer.
Further Study Information
- Determine the efficacy of combination chemotherapy comprising modified docetaxel, cisplatin, fluorouracil, and leucovorin calcium with bevacizumab, as measured by 6-month progression-free survival (PFS), in patients with locally recurrent, unresectable, or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma.
- Determine the safety of this regimen in these patients.
- Determine other measures of efficacy of this regimen, including response rate, median PFS, and overall and 1-year survival, in these patients.
OUTLINE: This is an open-label, nonrandomized study.
Patients receive bevacizumab IV over 30 minutes, docetaxel IV over 1 hour, and leucovorin calcium IV over 30 minutes on days 1, 15, and 29; fluorouracil IV continuously on days 1-3, 15-17, and 29-31; and cisplatin IV over 30 minutes on days 3, 17, and 31. Courses repeat every 6 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study.
- Histologically or cytologically confirmed gastric or esophageal adenocarcinoma
- Gastroesophageal junction adenocarcinoma classified according to Siewert's class type I-III allowed
- Locally recurrent, metastatic, or unresectable disease
- If recurrent or metastatic disease is not histologically confirmed, then documentation by a second radiographic procedure (i.e., positron emission tomography scan or MRI in addition to CT scan) is required
- If the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation is required
- Measurable or nonmeasurable disease that can be radiographically evaluated
- Measurable disease is defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by high-resolution imaging
- Nonmeasurable disease is defined as disease that can be identified on radiology studies, but does not meet the criteria for measurable disease
- No brain or CNS metastases, including leptomeningeal disease
- ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
- WBC ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9.0 g/dL
- Bilirubin normal
- Creatinine ≤ 1.5 mg/dL
- Alkaline phosphatase (AP), AST, and ALT must meet 1 of the following criteria:
- AP normal AND AST and ALT ≤ 5 times upper limit of normal (ULN)
- AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN
- AP ≤ 5 times ULN AND AST and ALT normal
- Urinalysis < 2+ proteinuria
- Urine protein/urine creatinine ratio < 1.0
- PT (INR) ≤ 1.5 and PTT ≤ 3 seconds above ULN (if patient not on anticoagulation)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- No peripheral neuropathy > grade 1
- No other neoplastic disease within the past 3 years, except basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer
- No significant traumatic injury within the past 28 days
- No abdominal fistula, gastrointestinal bleeding, or intraabdominal abscess within the past 6 months
- No serious, nonhealing wound, ulcer, or bone fracture
- Blood pressure ≤ 150/100 mm Hg
- No significant cardiac disease, including any of the following:
- Unstable angina
- New York Heart Association class II-IV heart disease
- Congestive heart failure
- Myocardial infarction within the past 6 months
- No stroke or cerebrovascular accident within the past 6 months
- No clinically significant peripheral vascular disease
- No clinically significant hearing loss or ringing in the ears
- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
- No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
PRIOR CONCURRENT THERAPY:
- Recovered from prior therapy
- No prior chemotherapy for metastatic or unresectable disease
- No prior docetaxel, cisplatin, bevacizumab, or any other novel biologic antiangiogenic agent
- More than 6 months since prior fluorouracil
- More than 6 months since prior adjuvant therapy (including chemotherapy and/or chemoradiotherapy)
- More than 7 days since prior minor surgery, including fine-needle aspiration, core biopsy, laparoscopy, or mediport placement
- More than 28 days since prior major surgery or open biopsy
- No concurrent major surgery
- No other concurrent chemotherapy or anticancer therapy
- No concurrent immunotherapy or radiotherapy
- Concurrent full-dose anticoagulants allowed if the following criteria are met:
- In-range INR (usually 2-3) on a stable dose of warfarin or low molecular weight heparin
- No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
Trial Lead Organizations/Sponsors
Memorial Sloan-Kettering Cancer CenterNational Cancer Institute
|Minaxi Jhawer||Principal Investigator|
|Memorial Sloan-Kettering Cancer Center|
|Minaxi Jhawer, MD||Ph: 212-639-3787|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00403468
Information obtained from ClinicalTrials.gov on November 20, 2012
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