Second-Line Docetaxel + ASA404 for Advanced Urothelial Carcinoma

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: Docetaxel; Drug: ASA404

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

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Hoosier Cancer Research Network
• Collaborators: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: February 18, 2010
• First Submitted That Met QC Criteria: February 18, 2010
• First Posted (Estimate): February 19, 2010

Study Record Updates

• Last Update Posted (Estimate): August 19, 2015
• Last Update Submitted That Met QC Criteria: August 17, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Advanced Urothelial Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Vadimezan
• Other Study ID Numbers: GU09-144