second-line docetaxel + asa404 for advanced urothelial carcinoma

Conditions: Urothelial Carcinoma

Summary: the purpose of this study is to explore the safety and activity of docetaxel + asa404 as second-line chemotherapy in patients with advanced urothelial carcinoma.

outline: this is a multi-center study. 21 day cycle treatment regimen: * docetaxel iv 75 mg/m2 over approximately 60 minutes on day 1 * asa404 (given after docetaxel) iv 1800 mg/m2 over approximately 20 minutes on day 1 treatment will continue until disease progression or intolerable treatment related adverse effects. karnofsky performance status of ≥ 70% within 7 days prior to registration for protocol therapy. life expectancy: not specified hematopoietic: * hemoglobin (hgb) \> 9 g/dl * platelets \> 100 k/mm3 * absolute neutrophil count (anc) \> 1.5 k/mm3 * inr or prothrombin time (pt) \< 1.5 x uln hepatic: * bilirubin \< 1.5 x uln * aspartate aminotransferase (ast, alt) \< 2.5 x uln renal: * calculated creatinine clearance of \> 45 cc/min using the cockcroft-gault formula cardiovascular: * no congestive heart failure (ny heart association class iii or iv) * no myocardial infarction within 12 months of study registration for protocol therapy or with implanted cardiac pacemaker * no unstable or poorly controlled angina pectoris, including prinzmetal variant angina pectoris

Eligibility criteria:
inclusion criteria: * histological or cytological proof of transitional cell carcinoma (tcc) of the bladder, urethra, ureter, or renal pelvis (urothelial carcinoma). histology may be mixed, but still requires a component of tcc. * measurable disease according to recist (version 1.1) and obtained by imaging within 30 days prior to registration for protocol therapy. note: sites of measurable disease can not be within a previously irradiated site. * written informed consent and hipaa authorization for release of personal health information. * age \> 18 years at the time of consent. * must have received only one prior chemotherapy regimen, which must have included one of the following chemotherapeutic agents: cisplatin, carboplatin, or gemcitabine. note: prior chemotherapy may have been administered in the perioperative (neoadjuvant/adjuvant) or advanced/metastatic setting. patients may have received prior treatment with paclitaxel. * females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 12 weeks after treatment discontinuation. * females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy. * females must not be breastfeeding. exclusion criteria: * no prior treatment with docetaxel. * no symptomatic brain metastases. patients with neurological symptoms must undergo a head ct scan or brain mri to exclude brain metastasis. note: patients with treated brain metastasis must be off steroids and have completed radiation at least 14 days prior to registration for protocol therapy. * no prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, gleason \< grade 7 prostate cancers, or other cancers for which the patient has been disease-free for at least 5 years * no treatment with any investigational agent or chemotherapeutic agent within 30 days prior to registration for protocol therapy. * no radiotherapy within 14 days prior to registration for protocol therapy. patients must have recovered from all radiotherapy-related toxicities. * no major surgery within 30 days prior to registration for protocol therapy (major surgery is defined by the use of general anesthesia). * no minor surgery 14 days prior to registration for protocol therapy. note: insertion of a vascular access device is allowed. * no history of any medical condition resulting in ≥ ctc grade 2 dyspnea. * patients without long qt syndrome * no history of labile hypertension or poor compliance with anti-hypertensive regimen note: no patients with systolic bp \>140 mm hg and/or diastolic bp \> 90 mm hg while on medication for hypertension. * no presence of atrial tachyarrhythmia (e.g., atrial fibrillation, atrial flutter, multifocal atrial tachycardia, supraventricular tachycardia) if not effectively rate-controlled. * no history of a sustained ventricular tachycardia * no history of ventricular fibrillation or torsades de pointes * no right bundle branch block and left anterior or posterior hemiblock (bifascicular block) * no bradycardia defined as heart rate \<50 beats per minute * no concomitant use of drugs with risk of causing torsades de pointes. * no concomitant use of drugs that are inducers and inhibitors of ugt1a9 and ugt2b7.

Keywords: advanced urothelial carcinoma