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Second-Line Docetaxel + ASA404 for Advanced Urothelial Carcinoma

Phase 2
Withdrawn
Conditions
Urothelial Carcinoma
Interventions
Drug: Docetaxel
Drug: ASA404
Registration Number
NCT01071928
Lead Sponsor
Hoosier Cancer Research Network
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

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Docetaxel and ASA404 in CombinationDocetaxel-
Docetaxel and ASA404 in CombinationASA404-
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
To evaluate progression-free survival in patients with advanced urothelial carcinoma12 months
To evaluate survival at 1 year from start of treatment in patients with advanced urothelial carcinoma treated with docetaxel + ASA404 as second line therapy12 months
To evaluate the safety of docetaxel and ASA404 combination, as measured by the NCI Common Toxicity Criteria version 3.012 months
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