Phase II study of neoadjuvant cisplatin and gemcitabine plus sorafenib for patients with transitional cell carcinoma of the bladder. - Sorafenib-CG in TCC of the bladder

• Conditions: Muscle-invasive transitional cell carcinoma of the bladder at clinical stage T>/=2N0.; MedDRA version: 9.1Level: LLTClassification code 10005084

• Registration Number: EUCTR2010-022653-41-IT
• Lead Sponsor: ISTITUTO NAZIONALE PER LA CURA TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-04
• Last Update Posted: 7 October 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Age =18 years. 2. ECOG Performance Status of at least 1. 3. Confirmation of TCC histology by trans-urethral resection of the bladder (TURB). 4. Confirmation of muscle-invasive (T=2) disease at TURB or clinical stage T3 and T4 (e.g. T2 patients will not be eligible without an histological documentation of invasive disease). Confirmation of TCC histology based on pathologic review at Fondazione INT Milan will be required in all cases. 5. Clinically node-negative (cN0) disease. 6. No prior systemic therapies (patients who received intravesical therapy for superficial disease will be eligible). 7. No prior therapy with sorafenib and no use of any investigational agents within 4 weeks of study entry. 8. Subjects must provide written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Documentation of nodal or distant metastatic disease. 2. Urothelial carcinoma of the upper urinary tract. 3. Prior malignancy. NOTE: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. 4. Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to: - Active peptic ulcer disease - Known intraluminal metastatic lesion/s with suspected bleeding - Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn’s disease), or other gastrointestinal conditions with increased risk of perforation - History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. 5. Clinically significant gastrointestinal abnormalities that may increase the risk of bleeding or may affect absorption of investigational product including, but not limited to: - Malabsorption syndrome - Major resection of the stomach or small bowel. 6. Presence of uncontrolled infection (grade >2 NCI-CTC version 4.0). 7. Prolongation of corrected QT interval (QTc) > 450 msecs. 8. History of any one or more of the following cardiovascular conditions within the past 6 months. - Cardiac angioplasty or stenting. - Myocardial infarction. - Unstable angina. - Coronary artery by-pass graft surgery. - Symptomatic peripheral vascular disease. - Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA). 9. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg]. NOTE: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. The mean SBP/DBP values from each blood pressure assessment must be <140/90mmHg in order for a subject to be eligible for the study. 10. History of cerebrovascular accident, pulmonary embolism or deep venous thrombosis (DVT) within the past 6 months. 11. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major). 12. Evidence of active bleeding or bleeding diathesis. 13. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results. 14. Any condition that is unstable or could jeopardize the safety of the patients and their compliance in the study. 15. Patients unable to swallow oral medications. 16. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drug chemically related to study drug. 17. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics). 18. Patients undergoing renal dialysis. 19. Pregnancy or lactation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the trial is to evaluate the activity (pathological Complete Response - pCR) of the combination of cisplatin and gemcitabine with sorafenib as neoadjuvant therapy for patients with muscle-invasive (T2-4) node-negative TCC of the bladder.;Secondary Objective: To evaluate the safety and tolerability of the combination of CG + sorafenib in a population of chemotherapy-na?ve TCC.;Primary end point(s): Pathological complete response (pCR) rate.