A Double Blind Randomised Study of Lapatinib and Placebo in Metastatic TCC of the Urothelium

DISEASE CHARACTERISTICS:

* Histologically confirmed transitional cell carcinoma of the bladder

  * Stage IV disease
  * Metastatic or locally advanced disease
* HER1- and/or HER2-positive disease, defined by the following criteria:

  * 2+ or 3+ intensity on IHC
* Able to commence the study treatment within 10 weeks of completing chemotherapy
* Must have achieved objective response or stable disease following 4-8 courses of first-line chemotherapy

  * No progression with first-line chemotherapy for metastatic disease
  * Any widely accepted chemotherapy regimen for bladder cancer allowed
  * Patients who did not receive cisplatin are eligible

PATIENT CHARACTERISTICS:

* ECOG performance status 0-3
* ANC ≥ 1.0 x 10\^9/L
* Hemoglobin ≥ 8.0 g/dL
* Platelet count ≥ 75 x 10\^9/L
* ALT/AST \< 2 times upper limit of normal (ULN)
* Bilirubin \< 1.5 times ULN
* Serum creatinine ≤ 3.0 ULN AND/OR creatinine clearance ≥ 30 mL/min
* LVEF ≥ 50% (as assessed by quantitative echocardiogram or MUGA)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No current active hepatic or biliary disease, except for any of the following:

  * Gilbert's syndrome
  * Asymptomatic gallstones
  * Liver metastases
  * Stable chronic liver disease per investigator assessment
* No known hypersensitivity to the study medication
* No history of prior or concurrent other neoplasms, except for:

  * Any non life-threatening tumours that have been curatively treated.
  * Prostate cancer isolated to the prostate gland
* No significant cardiac disease, including any of the following:

  * Angina pectoris
  * Severe cardiac arrhythmia requiring medication
  * Severe conduction abnormalities
  * Clinically significant valvular disease
  * Cardiomegaly
  * Prior myocardial infarction
  * Ventricular hypertrophy
  * Congestive heart failure
  * Poorly uncontrolled hypertension (resting diastolic blood pressure \> 115 mm Hg)
  * Other cardiomyopathy
* No serious intercurrent medical or psychiatric illness
* No serious active infection

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No more than 1 line of prior chemotherapy for metastatic or locally advanced disease (neoadjuvant/adjuvant chemotherapy allowed)
* No more than 10 weeks since first-line chemotherapy
* No prior lapatinib ditosylate
* No prior radiotherapy to the indicator lesion(s) (newly arising lesions in previously irradiated areas allowed)
* At least 14 days since prior and no concurrent CYP3A4 inducers, including but not limited to, any of the following:

  * Antibiotics (all rifamycin class agents \[e.g., rifampicin, rifabutin, rifapentine\])
  * Anticonvulsants (phenytoin, carbamazepine, barbiturates \[e.g., phenobarbital\])
  * Oral glucocorticoids (cortisone \[\> 50 mg\], hydrocortisone \[\> 40 mg\], prednisone \[\> 10 mg\], methylprednisolone \[\> 8 mg\], dexamethasone \[\> 2 mg²\])
  * St. John's wort or modafinil
* At least 7 days since prior and no concurrent CYP3A4 inhibitors, including but not limited to, any of the following:

  * Antibiotics (clarithromycin, erythromycin, troleandomycin)
  * Antifungals (itraconazole, ketoconazole, fluconazole \[\>150 mg daily\], voriconazole)
  * Antiretrovirals/protease inhibitors (delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir)
  * Calcium channel blockers (verapamil, diltiazem)
  * Antidepressants (nefazodone, fluvoxamine)
  * Gastrointestinal agents (cimetidine, aprepitant)
  * Grapefruit, grapefruit juice
* At least 6 months since prior and no concurrent amiodarone
* No concurrent radical or curative therapy (radiotherapy or surgery) at the end of first-line treatment (palliative radiotherapy allowed)
* No other concurrent experimental or investigational drugs
* No other concurrent anticancer treatment, including cytotoxic or specific immune therapy