Cisplatin, Gemcitabine Hydrochloride, and Sorafenib Tosylate in Treating Patients With Transitional Cell Cancer of the Bladder

Bladder Cancer Clinical Trial

Official title:

A Phase II Study of Neoadjuvant Cisplatin and Gemcitabine Plus Sorafenib for Patients With Transitional-Cell Carcinoma of the Bladder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01222676
• Other study ID #: ITA-MIL-IRCCS-INT-52/10
• Secondary ID: CDR0000686602EUD
• Status: Recruiting
• Phase: Phase 2
• First received: October 15, 2010
• Last updated: August 9, 2013
• Start date: October 2010

Study information

• Verified date: October 2010
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Giving cisplatin and gemcitabine hydrochloride together with sorafenib tosylate may kill more tumor cells. Giving them before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving cisplatin and gemcitabine hydrochloride together with sorafenib tosylate works in treating patients with node-negative transitional cell cancer of the bladder.

Description:

OBJECTIVES:

Primary

• To evaluate the activity (pathological complete response) of neoadjuvant cisplatin and gemcitabine hydrochloride in combination with sorafenib tosylate in patients with muscle-invasive, node-negative transitional cell carcinoma of the bladder.

Secondary

• To evaluate the safety and tolerability of this regimen in these patients.

• To determine the potential biological correlates of disease response and drug activity in tumor tissue samples before and after treatment.

• To evaluate the correlation between fludeoxyglucose F 18 positron emission tomography (18FDG-PET) and standard computed tomography (CT) results and the ability of changes of 18FDG-PET (as measured by EORTC criteria for response) to predict subsequent favorable response to treatment (pathological complete response rate and progression-free survival).

OUTLINE: Patients receive cisplatin IV over 20-30 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Patients also receive sorafenib tosylate twice daily on days 1-21. starting on day 1and continuing up to Treatment repeats every 21 days for 2 courses. Patients are reassessed after course 2, those who experience disease progression or deemed unresectable are off study. Other patients continue the treatment for 2 more courses*.

NOTE: *Sorafenib tosylate are stopped 14 days prior to planned cystectomy.

No more than 30 days after completion of neoadjuvant therapy, patients undergo planned radical cystectomy with pelvic lymph-node dissection off study.

Tumor tissue and serum samples may be collected during study for additional biological studies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Confirmed transitional cell carcinoma (TCC) of the bladder at the time of diagnostic transurethral resection of the bladder tumor (TURB)*

• Muscle-invasive (T = 2) disease at TURB OR clinical stage T3 or T4 disease (e.g., T2 patients will not be eligible without a histological documentation of invasive disease)

• NOTE: *Confirmation of TCC histology based on pathologic review at Fondazione Istituto Nazionale dei Tumori Milan will be required in all cases.

• Clinically node-negative (cN0) disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• WBC = 2,000/µL

• ANC = 1,500/µL

• Platelet count = 100,000/µL

• Serum creatinine = 1.5 mg/dL

• AST/ALT < 2.5 times upper limit of normal (ULN) (< 5 times ULN if due to hepatic metastases)

• Total bilirubin < 1.5 times ULN

• Not pregnant

• Negative pregnancy test

• Fertile patients must use effective contraception

• Negative serology for the following infectious diseases:

• HIV type 1 or 2

• Hepatitis B surface antigen (active carriers)

• Hepatitis C

PRIOR CONCURRENT THERAPY:

• No prior systemic therapies except for intravesical therapy for superficial disease

• No prior sorafenib tosylate

• No prior systemic chemotherapy

• At least 4 weeks since prior investigational agents

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Urinary Bladder Neoplasms

Intervention

Drug:
• cisplatin

• gemcitabine hydrochloride

• sorafenib tosylate

Other:
• imaging biomarker analysis

• laboratory biomarker analysis

Procedure:
• computed tomography

• neoadjuvant therapy

Radiation:
• fludeoxyglucose F 18

Locations

Country	Name	City	State
Italy	Fondazione Istituto Nazionale dei Tumori	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response			No
Secondary	Safety and tolerability			Yes
Secondary	Potential biological correlates of disease response and drug activity in tumor tissue samples before and after therapy			No
Secondary	Correlation between 18FDG-PET and standard CT results			No