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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01222676
First received: October 15, 2010
Last updated: August 9, 2013
Last verified: October 2010
  Purpose

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.


Condition Intervention Phase
Bladder Cancer
Drug: cisplatin
Drug: gemcitabine hydrochloride
Drug: sorafenib tosylate
Other: imaging biomarker analysis
Other: laboratory biomarker analysis
Procedure: computed tomography
Procedure: neoadjuvant therapy
Radiation: fludeoxyglucose F 18
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Neoadjuvant Cisplatin and Gemcitabine Plus Sorafenib for Patients With Transitional-Cell Carcinoma of the Bladder

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pathological complete response [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability [ Designated as safety issue: Yes ]
  • Potential biological correlates of disease response and drug activity in tumor tissue samples before and after therapy [ Designated as safety issue: No ]
  • Correlation between 18FDG-PET and standard CT results [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: October 2010
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01222676

Locations
Italy
Fondazione Istituto Nazionale dei Tumori Recruiting
Milan, Italy, 20133
Contact: Contact Person    39-2-2390-2359    roberto.salvioni@istitutotumori.mi.it   
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Principal Investigator: Roberto Salvioni, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT01222676     History of Changes
Other Study ID Numbers: ITA-MIL-IRCCS-INT-52/10, CDR0000686602, EUDRACT-2010-022653-41, EU-21077
Study First Received: October 15, 2010
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
transitional cell carcinoma of the bladder
stage II bladder cancer
stage III bladder cancer
stage IV bladder cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gemcitabine
Sorafenib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014