Vandetanib, Oxaliplatin, and Docetaxel in Advanced Cancer of the Esophagus or Gastroesophageal Junction

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction
• Patients with locally advanced, unresectable disease are eligible provided they failed prior radiation-based therapy
• At least one measurable lesion
• No active CNS metastases as indicated by clinical symptoms, cerebral edema, or progressive growth
• Patients with a clinical history of CNS metastases or cord compression are eligible provided they have been definitively treated and are clinically stable for ≥ 4 weeks (if treated with whole brain irradiation) or for ≥ 2 weeks (if treated with gamma knife therapy)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy > 12 weeks
• Hemoglobin > 9.5 g/dL
• ANC > 1,500/μL
• Platelets > 100,000/μL
• Total bilirubin normal
• Creatinine < 1.5 times upper limit of normal (ULN)
• Creatinine clearance ≥ 30 mL/min
• AST, ALT, and alkaline phosphatase (AP) must meet one of the following criteria:
• AST or ALT ≤ 5 times ULN AND AP normal
• AST or ALT ≤ 1.5 times ULN AND AP ≤ 2.5 times ULN
• AST or ALT normal AND AP ≤ 5 times ULN
• Potassium between 4 mmol/L and the upper limit of CTCAE grade 1 (supplementation allowed)
• Calcium (ionized or adjusted for albumin) and magnesium normal (supplementation allowed)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
• No significant cardiovascular events within the past 3 months, including the following:
• Myocardial infarction
• Superior vena cava syndrome
• NYHA class II-IV congestive heart failure
• No cardiac disease that, in the opinion of the investigator, may increase the risk of ventricular arrhythmia
• No prior arrhythmia (e.g., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (CTCAE grade 3)
• Atrial fibrillation allowed provided it is controlled with medication
• No asymptomatic sustained ventricular tachycardia
• No hypertension not controlled by medical therapy (i.e., systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm Hg)
• No QTc prolongation with other medication that required discontinuation of that medication
• No congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
• QTc is < 480 with Bazett's correction on screening ECG at baseline
• No presence of left bundle branch block
• No active diarrhea > CTC grade 1
• No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No prior allergic reactions to compounds of similar chemical or biologic composition to study drugs
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, would preclude study participation
• No other malignancy within the past 5 years, except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations ≥ 3 months apart, with the most recent evaluation performed within the past 4 weeks
• No peripheral neuropathy > grade 1
• No blood donation during and for 3 months after completion of study treatment
• No severe or uncontrolled systemic disease or other medical condition, including mental illness or substance abuse, that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• No prior systemic therapy for metastatic disease
• Prior chemotherapy given as part of a definitive treatment plan (e.g., neoadjuvant or adjuvant chemotherapy or concurrent chemoradiotherapy) allowed
• More than 6 months since prior oxaliplatin and docetaxel as neoadjuvant or adjuvant therapy
• More than 4 weeks since prior major surgery, chemotherapy, radiotherapy, investigational agents, or other cancer therapy
• No prior anti-VEGF or EGFR therapy, including bevacizumab
• More than 2 weeks since prior and no concurrent potent CYP3A4 inducers (e.g.,rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, and Hypericum perforatum [St. John's wort])
• More than 2 weeks since prior and no concurrent medications known to cause QTc prolongation or to induce torsades de pointes
• No other concurrent chemotherapy, systemic antineoplastic therapy, or investigational therapy
• No concurrent radiotherapy, unless for local control of bone pain
• No concurrent cold cap or iced mouth rinses for prevention of alopecia or stomatitis
• No concurrent routine prophylactic use of granulocyte colony-stimulating factor (G-CSF) or pegfilgrastim
• No concurrent vitamin B6 supplementation, except as part of a standard multivitamin