Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery
Conditions
Stage III Bladder Urothelial Carcinoma - Stage IV Bladder Urothelial Carcinoma
Conditions: official terms
Carcinoma - Carcinoma, Transitional Cell
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Eribulin Mesylate Type: Drug
Name: Gemcitabine Hydrochloride Type: Drug
Overall Status
Recruiting
Summary
This phase II trial studies how well gemcitabine hydrochloride and eribulin mesylate work in treating patients with bladder cancer that has spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Detailed Description
PRIMARY OBJECTIVES:

I. To estimate the objective response rate of gemcitabine (gemcitabine hydrochloride)-eribulin (eribulin mesylate) (GE) when given to cisplatin ineligible patients with advanced or unresectable urothelial carcinoma who have not received any prior chemotherapy for the advanced disease.

SECONDARY OBJECTIVES:

I. To estimate the median progression-free survival (PFS). II. To summarize the toxicity profile (using Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 criteria) of the GE regimen in these patients.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and eribulin mesylate IV over 2-5 minutes. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 36 months.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Patients must have locally advanced or metastatic urothelial carcinoma of the bladder that is not amenable to curative surgical treatment

- Patients must have histologically confirmed urothelial carcinoma of the bladder

- Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

- Patients must be ineligible for treatment with cisplatin, based on one of:

- Calculated creatinine clearance (CrCl) >= 30 and < 60 mL/min (Cockcroft-Gault)

- CTCAE grade (Gr) >= 2 hearing loss

- CTCAE Gr >= 2 neuropathy

- Patients must not have received prior systemic therapy for their advanced cancer; prior intravesical therapy completed 4 weeks prior to enrollment and adjuvant/neoadjuvant chemotherapy completed more than 6 months prior to diagnosis of advanced disease are permitted

- Zubrod performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 3 months

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin < 1.5 times the upper limit of normal (x ULN) for the institution

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal

- Creatinine clearance; calculated creatinine clearance (CrCl) >= 30 mL/min and < 60 mL/min (Cockroft-Gault) unless the patient qualified based on hearing loss or neuropathy

- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of gemcitabine and eribulin administration

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients with upper tract urothelial carcinoma are excluded; however, patients with clinical evidence of both upper and lower tract urothelial cancer may be enrolled provided they meet all other criteria

- Patients with non-urothelial histologies are excluded; squamous and small cell differentiations in less than 5% of the tumor are allowed

- Patients who have had chemotherapy for the treatment of the advanced or unresectable urothelial cancer of the bladder are not eligible; patients who were previously treated for local disease must not have received radiotherapy or chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have received neoadjuvant or adjuvant chemotherapy must have completed treatment at least 6 months prior to diagnosis of metastatic disease

- Patients who are receiving any other investigational agents

- Patients with known brain metastases should be excluded from this clinical trial

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine and eribulin

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with eribulin and gemcitabine

- Human immunodeficiency virus (HIV)-positive patients with inadequate cluster of differentiation (CD)4 counts or those who are on combination antiretroviral therapy with strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) effects are ineligible for this trial

- Patients with baseline corrected QT (QTc) prolongation greater than grade 1 are excluded from this study; patients with grade 1 QTc elevation are eligible but must be monitored with electrocardiogram (ECG) (EKG) exams, for the first 3 cycles of treatment; eribulin time to maximum concentration (Cmax) after infusion is about 10 minutes, and half life is 40 minutes; ECG (EKG) should be performed between 10 to 40 minutes after eribulin administration (on day 1 and day 8 of treatment); continued ECG (EKG) monitoring beyond cycle 3 can be done at the discretion of the treating physician

- Patients with congenital long QT syndrome are excluded from this study

- Other medications known to prolong QT interval should be discontinued and if not possible, patient is excluded from this study
Locations
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Status: Recruiting
Contact: Sarmad Sadeghi - 323-865-0553 - sarmad.sadeghi@usc.edu
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Status: Recruiting
Contact: Sarmad Sadeghi - 323-865-0451
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Status: Recruiting
Contact: Primo N. Lara - 916-734-3089
MedStar Georgetown University Hospital
Washington, District of Columbia, United States
Status: Recruiting
Contact: George K. Philips - 202-444-0381
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Status: Recruiting
Contact: Walter M. Stadler - 773-834-7424
UC Comprehensive Cancer Center at Silver Cross
New Lennox, Illinois, United States
Status: Recruiting
Contact: Walter M. Stadler - 773-834-7424
Case Western Reserve University
Cleveland, Ohio, United States
Status: Recruiting
Contact: Matthew M. Cooney - 800-641-2422
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Status: Recruiting
Contact: Robert Dreicer - 216-445-4623 - dreicer@ccf.org
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Status: Recruiting
Contact: Rahul A. Parikh - 412-647-8073
Start Date
December 2014
Sponsors
National Cancer Institute (NCI)
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page