Sorafenib in Urothelium Cancer of Bladder

Prospektiv, Randomisierte, Doppelblinde, Multizentrische Phase-II- Studie Zum Vergleich Der Wirksamkeit Einer Chemotherapie Mit Gemcitabin Plus Cisplatin Und Sorafenib (BAY 43-9006) Versus Gemcitabin Plus Cisplatin Und Plazebo in Der Therapie Des Lokal Fortgeschrittenen Bzw. Metastasierten Urothelkarzinoms AB 31/05 - RUTT 204 - SUSE

The purpose of this study is to evaluate the use of Sorafenib additionally to gemcitabine and cisplatin in bladder cancer.

Study Overview

• Status: Terminated
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Sorafenib; Drug: Placebo

Detailed Description

A controlled, double-blind, randomized study to evaluate the influence of Sorafenib in bladder cancer patients additionally to chemotherapy with gemcitabine and cisplatin compared to placebo.

• Study Type: Interventional
• Enrollment (Actual): 98
• 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:

Men and Women > 18 years

• Condition ECOG(Eastern Cooperative Oncology Group) 0-1
• Life expectancy at least 12 weeks
• Women in conceptional age: negative pregnancy test and adequate contraception (oral contraceptive, spiral); at men adequate contraception of the man (condom use) to 3 months after discontinuation of therapy with sorafenib
• Histologically or cytologically proven urothelial carcinoma of the bladder or upper urinary tract
• Locally advanced or metastatic urothelial carcinoma of the bladder or upper urinary tract (T3b,T4/ N+/M+)
• At least one unidimensional measurable lesion on CT(Computed Tomography) or MRI(Magnetic resonance imaging) according to RECIST(Response Evaluation Criteria in Solid Tumors) criteria
• Adequate hematologic, renal, hepatic and coagulation-physiological functions
• Leukocytes > 1.500 cells /ml (per milliliter)
• Hemoglobin >9g/dl(gram per deciliter)
• Platelet > 100000 /ml
• Serum creatinine < 2 x upper limit of normal or creatinine clearance ≥ 45 ml/min (milliliter per minute)
• Total Bilirubin < 1,5 x upper limit of normal
• GOT/GPT (glutamate-oxalacetate-transaminase/glutamate-pyruvate-transaminase) < 2,5 x upper limit of normal, at liver metastases < 5x upper limit of normal
• alkaline phosphates < 5 x upper limit of normal
• Amylase/ Lipase < 1,5 x upper limit of normal
• INR(International Normalized Ratio) und PTT(Partial Thromboplastin Time) < 1,5 x upper limit of normal
• Informing the patient about the study and the present written consent to participate after clarification in accordance with the stipulations of AMG(german drug law), and the principles of the Ethics Committee ("informed consent").

Exclusion Criteria:

• Absence of the above inclusion criteria
• Dialysis after nephrectomy
• Patients with brain tumors and / or brain metastases
• Previous or existing serious cardiovascular (grade III - IV according to NYHA(New York Heart Association)) disease, active angina pectoris or ischemia, myocardial infarction within 6 months prior to enrollment, or patients with serious cardiac arrhythmias requiring antiarrhythmic therapy (beta blockers and digoxin are permitted)
• Patients with uncontrolled high blood pressure, systolic blood pressure> 150 mm Hg or diastolic pressure> 90 mmHg despite optimal medical treatment
• Patients with thrombotic or embolic events such as stroke or pulmonary embolism
• Patients with recently or known bleeding diathesis
• Known significant neurological or psychiatric diseases including dementia and epileptic seizures
• Serious inflammatory eye disease, hearing impairment
• Pulmonary (pO2(Blood oxygen) <60 mm Hg(Millimeters of mercury)), hematopoietic (eg(exempli gratia) severe bone marrow aplasia), hepatic or renal disease
• Patients with poorly controlled diabetes mellitus
• Serious bacterial or fungal infections(>Grade 2 NCI-CTC(National Cancer Institute-Common Terminology Criteria) Version 3)
• chronic hepatitis B or C, HIV(human immunodeficiency virus) infection
• Autoimmune disease
• Allergic reactions to be used in respect of a drug
• prior organ transplantation
• prior autologous bone marrow transplant or stem cell transferred within the last 4 months before study
• Manifesto, second malignancy or other malignancy within the past 5 years (except basal cell carcinoma, carcinoma in situ of the cervix, incidental prostate carcinoma)
• Pregnancy or breast-feeding
• Lack of cooperation and the ability to cooperate, predictable problems with the aftercare, psychiatric disorders, substance abuse, lack of capacity of the patient
• Participation in other treatment studies in the last 4 weeks
• Previous treatment with chemotherapy or immunotherapy
• Simultaneous treatment with other anti-tumor therapies after study start
• Intravesical chemotherapy within the last 4 weeks
• Irradiation within the last 4 weeks
• Previous radiation therapy, when all were irradiated to the assessment of tumor response used lesions
• Complex operations, open biopsy or significant injuries within the last 4 weeks before study
• Serious wound healing disorder, ulcers or bone fractures in the last 4 weeks before study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Day 3-21 2x2 800 mg(milligram) daily; Other Names: Plazebo
Active Comparator: Sorafenib	Drug: Sorafenib; Day 3-21 2x2 800 mg(milligram) daily; Other Names: Prüfsubstanz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	5 years
Time to progression	5 years
Response rates, time of response	5 years
Evaluation and comparison in both treatment arms	5 years

Collaborators and Investigators

• Sponsor: Association of Urologic Oncology (AUO)
• Collaborators: University Hospital, Essen
• Investigators: Study Chair: Susanne Krege, Prof. Dr., Universität Duisburg-Essen

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimate): October 6, 2010

Study Record Updates

• Last Update Posted (Estimate): September 8, 2011
• Last Update Submitted That Met QC Criteria: September 7, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Bladder cancer; Chemotherapy; Urothelium cancer
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: AB 31/05 RUTT 204; 2005-006098-29 (EudraCT Number)