Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery
Condition: Metastatic Ureter Carcinoma; Metastatic Urethral Carcinoma; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Ureter Cancer AJCC v7; Stage III Urethral Cancer AJCC v7; Stage IV Bladder Urothelial Carcinoma AJCC v7; Stage IV Ureter Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Urothelial Carcinoma; Urethral Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Urethral Neoplasms; Ureteral Neoplasms
Intervention: Eribulin Mesylate; Gemcitabine Hydrochloride
Intervention description: Given IV; Given IV
Intervention MeSH terms: Gemcitabine; Halichondrin B
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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