Second-Line Docetaxel + ASA404 for Advanced Urothelial Carcinoma
Second-Line Docetaxel + ASA404 for Advanced Urothelial Carcinoma
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
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.