Urothelial Carcinoma
Conditions
Keywords
Advanced Urothelial Carcinoma
Brief 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.
Detailed description
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
Interventions
DRUGDocetaxel
Docetaxel IV 75 mg/m2 over approximately 60 minutes on Day 1
DRUGASA404
ASA404 (given after Docetaxel)IV 1800 mg/m2 over approximately 20 minutes on Day 1
Sponsors
Novartis Pharmaceuticals
Hoosier Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the best overall response rate (as measured by RECIST version 1.1) of docetaxel + ASA404 as second line therapy in patients with advanced urothelial carcinoma. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate progression-free survival in patients with advanced urothelial carcinoma | 12 months |
| To evaluate survival at 1 year from start of treatment in patients with advanced urothelial carcinoma treated with docetaxel + ASA404 as second line therapy | 12 months |
| To evaluate the safety of docetaxel and ASA404 combination, as measured by the NCI Common Toxicity Criteria version 3.0 | 12 months |
Outcome results
None listed