Carboplatin and Gemcitabine Hydrochloride With or Without Vandetanib as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Urinary Tract Cancer

Inclusion criteria

DISEASE CHARACTERISTICS: * Histologically confirmed transitional cell carcinoma (pure or mixed histology) of the urothelium (upper or lower urinary tract) * Cancers with other pathologies are permitted provided the dominant morphology is transitional cell carcinoma * Radiologically measurable disease according to RECIST v 1.1 criteria * Locally advanced and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy * Patient not suitable for cisplatin therapy, meeting 1 or more of the following criteria: * More than 75 years of age * ECOG performance status \> 2 * Creatinine clearance \< 30 mL/min * Clinically significant ischemic heart disease (myocardial infarction or unstable angina more than 3 but less than 12 months prior to date of randomization, symptomatic angina, or NYHA class I within 3 months prior to date of randomization) * Prior intolerance of cisplatin * Any other factor that, in the opinion of the investigator, indicates that cisplatin is not suitable for the patient (e.g., unilateral hearing loss) PATIENT CHARACTERISTICS: * See Disease Characteristics * ECOG performance status 0-2 * Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) * Creatinine clearance ≥ 30 mL/min * Potassium ≥ 4.0 mmol/L OR below the CTCAE grade 1 upper limit * Magnesium normal OR below the CTCAE grade 1 upper limit * Serum calcium ≤ 2.9 mmol/L (If serum calcium is \< lower limit of normal \[LLN\], then adjusted serum calcium must be ≥ LLN) * ALT/AST ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN (\< 5 times ULN if judged by the investigator to be related to liver metastases) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier-method contraception during and for 3 months (women) or 2 months (men) after completion of study therapy * No evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the investigator's opinion, makes it undesirable for the patient to participate in the trial or that would jeopardize compliance with the protocol * No significant risk of cardiac complications, defined as any of the following: * Clinically significant cardiovascular event (e.g., myocardial infarction, superior vena cava syndrome \[SVC\], NYHA classification of heart disease ≥ class II within 3 months prior to entry, or presence of cardiac disease that, in the opinion of the investigator, significantly increases the risk of ventricular arrhythmia) * History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia * Atrial fibrillation, controlled on medication, is not exclusionary * No QTc prolongation with other medications that requires discontinuation of that medication * No congenital long QT syndrome or first-degree relative with unexplained sudden death under 40 years of age * No QTc that is immeasurable or ≥ 480 msec on screening ECG * If a patient has a QTc interval ≥ 480 msec on screening ECG, the ECG screen may be repeated twice (at least 24 hours apart) and the average QTc from the three screening ECGs must be \< 480 msec in order for the patient to be eligible for the study * Patients who are receiving a drug that has a risk of Torsades de Pointes are excluded if QTc is ≥ 460 msec * No presence of left bundle branch block * No hypertension not controlled by medical therapy (systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 100 mm Hg) * No currently active diarrhea that, in the investigator's opinion, may affect the ability of the patient to either absorb vandetanib or to tolerate additional diarrhea episodes * No previous or current malignancies of other histology within the past 5 years except for carcinoma in situ of the cervix, adequately treated basal cell or squamous cell carcinoma of the skin, or prostate cancer PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 2 weeks since prior and no concurrent known potent CYP3A4 inducers (e.g., barbiturates, rifampicin, rifabutin, phenytoin, carbamazepine, troglitazone, phenobarbital, or St. John wort) or medication that has known adverse interactions with vandetanib * Dexamethasone (or equivalent) allowed as a pre-medication for chemotherapy * At least 4 weeks since prior major surgery and complete surgical wound healing * At least 30 days since prior and no other concurrent investigational agents * No prior chemotherapy (unless delivered perioperatively and completed \> 12 months prior to first presentation of recurrent disease) * No other concurrent anticancer drug