Second-Line Docetaxel + ASA404 for Advanced Urothelial Carcinoma

Study Overview
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Brief Summary
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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
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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

Official Title
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A Phase II Trial of Docetaxel Plus ASA404 as Second-Line Therapy in Patients With Advanced Urothelial Carcinoma: Hoosier Oncology Group GU09-144

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: Docetaxel
* Drug: ASA404


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel and ASA404 in Combination<br> | Drug: Docetaxel<br>* Docetaxel IV 75 mg/m2 over approximately 60 minutes on Day 1<br>Drug: ASA404<br>* ASA404 (given after Docetaxel)IV 1800 mg/m2 over approximately 20 minutes on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Urothelial Carcinoma