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

• ClinicalTrials.gov Identifier: NCT01222676
• Recruitment Status: Unknown
• First Posted: October 18, 2010
• Last Update Posted: August 12, 2013
• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Information provided by: National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: October 15, 2010
• First Posted Date: October 18, 2010
• Last Update Posted Date: August 12, 2013
• Study Start Date: October 2010
• Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 15, 2010): Pathological complete response
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 15, 2010)

• Safety and tolerability
• Potential biological correlates of disease response and drug activity in tumor tissue samples before and after therapy
• Correlation between 18FDG-PET and standard CT results

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cisplatin, Gemcitabine Hydrochloride, and Sorafenib Tosylate in Treating Patients With Transitional Cell Cancer of the Bladder
• Official Title: A Phase II Study of Neoadjuvant Cisplatin and Gemcitabine Plus Sorafenib for Patients With Transitional-Cell Carcinoma of the Bladder

Brief 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.

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Bladder Cancer

Intervention

• 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

• Study Arms: Not Provided
• Publications *: Necchi A, Lo Vullo S, Raggi D, Perrone F, Giannatempo P, Calareso G, Togliardi E, Nicolai N, Piva L, Biasoni D, Catanzaro M, Torelli T, Stagni S, Colecchia M, Busico A, Pennati M, Zaffaroni N, Mariani L, Salvioni R. Neoadjuvant sorafenib, gemcitabine, and cisplatin administration preceding cystectomy in patients with muscle-invasive urothelial bladder carcinoma: An open-label, single-arm, single-center, phase 2 study. Urol Oncol. 2018 Jan;36(1):8.e1-8.e8. doi: 10.1016/j.urolonc.2017.08.020. Epub 2017 Sep 12.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 15, 2010): 45
• Original Estimated Enrollment: Same as current
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT01222676
• Other Study ID Numbers: ITA-MIL-IRCCS-INT-52/10; CDR0000686602 ( Registry Identifier: PDQ (Physician Data Query) ); EUDRACT-2010-022653-41; EU-21077
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Collaborators: Not Provided

Investigators

• Principal Investigator: Roberto Salvioni, MD; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

• PRS Account: National Cancer Institute (NCI)
• Verification Date: October 2010