Cisplatin, Gemcitabine Hydrochloride, and Sorafenib Tosylate in Treating Patients With Transitional Cell Cancer of the Bladder
Bladder Cancer
Conditions: official terms
Carcinoma, Transitional Cell - Urinary Bladder Neoplasms
Conditions: Keywords
transitional cell carcinoma of the bladder, stage II bladder cancer, stage III bladder cancer, stage IV bladder cancer
Study Type
Study Phase
Phase 2
Study Design
Masking: Open Label, Primary Purpose: Treatment
Name: cisplatin Type: Drug
Name: gemcitabine hydrochloride Type: Drug
Name: sorafenib tosylate Type: Drug
Name: imaging biomarker analysis Type: Other
Name: laboratory biomarker analysis Type: Other
Name: computed tomography Type: Procedure
Name: neoadjuvant therapy Type: Procedure
Name: fludeoxyglucose F 18 Type: Radiation
Overall Status
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.
Detailed Description


- 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.


- 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both

- 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


- 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


- 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
Fondazione Istituto Nazionale dei Tumori
Milan, Italy
Status: Recruiting
Contact: Contact Person - 39-2-2390-2359 -
Start Date
October 2010
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
National Cancer Institute (NCI)
Record processing date processed this data on July 28, 2015 page