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

NCT ID: NCT01222676

Last Updated: 2013-08-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31

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.

Conditions

Bladder Cancer

Keywords

transitional cell carcinoma of the bladder; stage II bladder cancer; stage III bladder cancer; stage IV bladder cancer

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cisplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

sorafenib tosylate

Intervention Type: DRUG

imaging biomarker analysis

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

computed tomography

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

fludeoxyglucose F 18

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Principal Investigators

Roberto Salvioni, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Locations

Fondazione Istituto Nazionale dei Tumori

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

Contact Person

Role: primary

References

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.

Reference Type: DERIVED

PMID: 28911922 (View on PubMed)

Other Identifiers

CDR0000686602

Identifier Type: REGISTRY

Identifier Source: secondary_id

EUDRACT-2010-022653-41

Identifier Type: -

Identifier Source: secondary_id

EU-21077

Identifier Type: -

Identifier Source: secondary_id

ITA-MIL-IRCCS-INT-52/10

Identifier Type: -

Identifier Source: org_study_id