Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery
Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery
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.
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 on days 1 and 8. 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.
Inclusion Criteria:

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

 -  Patients must have histologically confirmed predominantly urothelial carcinoma of the
 bladder, ureter, or urethra

 -  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 a small cell component in their histology are excluded

 -  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, a second cancer
 diagnosis within the past 5 years, or a cancer undergoing any treatment, 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