Clinical trial NCT01071928: Second-Line Docetaxel + ASA404 for Advanced Urothelial Carcinoma
Official title: A Phase II Trial of Docetaxel Plus ASA404 as Second-Line Therapy in Patients With Advanced Urothelial Carcinoma: Hoosier Oncology Group GU09-144
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Urothelial Carcinoma
Keywords: Advanced Urothelial Carcinoma
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2010-02-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: 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.
timeFrame: 12 months
Secondary outcomes:
measure: To evaluate progression-free survival in patients with advanced urothelial carcinoma
timeFrame: 12 months
measure: To evaluate survival at 1 year from start of treatment in patients with advanced urothelial carcinoma treated with docetaxel + ASA404 as second line therapy
timeFrame: 12 months
measure: To evaluate the safety of docetaxel and ASA404 combination, as measured by the NCI Common Toxicity Criteria version 3.0
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Hoosier Cancer Research Network
name: Matthew Galsky, M.D.
role: STUDY_CHAIR
References: