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

Conditions

Bladder Cancer

Keywords

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

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.

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.

2017-09-127 citations

10.1016/j.urolonc.2017.08.020

Molecular features underlying response to neoadjuvant gemcitabine, cisplatin, and sorafenib (S-GC) in muscle-invasive urothelial bladder carcinoma (MIBC): Insights for trials of new agents combined with chemotherapy in the field.

Andrea Necchi, Daniele Raggi, Adele Busico, Loris De Cecco, Patrizia Giannatempo et al. (20 authors)

Journal of Clinical Oncology2017-05-20

10.1200/jco.2017.35.15_suppl.e16018

MP34-13 NEOADJUVANT SORAFENIB, GEMCITABINE, AND CISPLATIN (SGC) FOR MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER (MIUBC): FINAL RESULTS AND TRANSLATIONAL FINDINGS OF AN OPEN-LABEL, SINGLE-ARM, PHASE 2 STUDY.

Andrea Necchi, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Nicola Nicolai et al. (16 authors)

The Journal of Urology2017-04-01

10.1016/j.juro.2017.02.1030

Neoadjuvant sorafenib, gemcitabine, and cisplatin (SGC) for muscle-invasive urothelial bladder cancer (MIUBC): Final results and translational findings of an open-label, single-arm, phase II study.

Andrea Necchi, Salvatore Lo Vullo, Daniele Raggi, Patrizia Giannatempo, Nicola Nicolai et al. (19 authors)

Journal of Clinical Oncology2017-02-201 citations

10.1200/jco.2017.35.6_suppl.345

Updated analysis of circulating tumor cells (CTCs) in patients with urothelial cancer (UC) undergoing systemic treatment: Implications across the clinical stages.

Andrea Necchi, Emanuela Fina, Patrizia Giannatempo, Maurizio Colecchia, Chiara Iacona et al. (14 authors)

Journal of Clinical Oncology2014-05-20

10.1200/jco.2014.32.15_suppl.4544

Phase II study of neoadjuvant sorafenib plus cisplatin and gemcitabine (S-CG) for patients with muscle-invasive transitional cell carcinoma of the bladder (MIBC): Results at the end of first stage (NCT01222676).

Andrea Necchi, Patrizia Giannatempo, Luigi Mariani, Emanuela Fina, Nicola Nicolai et al. (20 authors)

Journal of Clinical Oncology2014-02-011 citations

10.1200/jco.2014.32.4_suppl.305

Quantification and molecular profiling of circulating tumor cells (CTCs) in urothelial cancer (UC) before and during systemic treatment: Implications across the clinical stages.

Andrea Necchi, Emanuela Fina, Patrizia Giannatempo, Maurizio Colecchia, Chiara Iacona et al. (13 authors)

Journal of Clinical Oncology2014-02-011 citations

10.1200/jco.2014.32.4_suppl.319

Interventions

DRUGcisplatin

DRUGgemcitabine hydrochloride

DRUGsorafenib tosylate

OTHERimaging biomarker analysis

OTHERlaboratory biomarker analysis

PROCEDUREcomputed tomography

PROCEDUREneoadjuvant therapy

RADIATIONfludeoxyglucose F 18

Study design

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion 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

Design outcomes

Primary

Measure	Time frame
Pathological complete response	—

Secondary

Measure	Time frame
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	—

Countries

Italy

Outcome results

None listed