Trial of Amrubicin as Second-Line Therapy in Patients With Advanced/Metastatic Refractory Urothelial Carcinoma
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms; Carcinoma, Transitional Cell
Intervention: Amrubicin
Intervention description: Patients will receive 35 mg/m2/day of amrubicin intravenously for 3 consecutive days as the initial dose starting on Day 1 of a 21-day cycle for up to 6 cycles
Intervention MeSH terms: Amrubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bladder Cancer; Urothelial Cancer; Chemotherapy; Second-line; Metastatic

Summary:

      The primary objective of this study is to determine in subjects with metastatic measurable
      bladder cancer (or urothelial cancers originating elsewhere in the genitourinary tract) who
      have progressed on 1 prior chemotherapeutic regimen the objective response rate to treatment
      with amrubicin. The secondary objectives will be to evaluate progression-free survival,
      survival at 1 year, and the safety of amrubicin as second-line therapy in patients with
      metastatic urothelial carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent

          2. Age > 18 years

          3. Karnofsky performance status of ≥ 80%

          4. Histological or cytological proof of transitional cell carcinoma of the urothelial
             tract. The primary site may include: urethra, bladder, ureters, and renal pelvis.

          5. Progressive advanced/metastatic disease despite prior chemotherapy:

               -  Patients may have received one prior chemotherapy regimen.

               -  Prior chemotherapy may have been administered in the perioperative setting
                  (neoadjuvant or adjuvant) or 1st line metastatic setting.

          6. Measurable disease according to RECIST 1.1

          7. Females of childbearing potential and males must be willing to use an effective method
             of contraception (hormonal or barrier method of birth control; abstinence) from the
             time consent is signed until 8 weeks after treatment discontinuation.

          8. Females of childbearing potential must have a negative pregnancy test within 7 days
             prior to being registered for protocol therapy.

          9. Adequate organ function including the following:

               -  Adequate bone marrow reserve: absolute neutrophil count (segmented and bands)
                  (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 mg/L,

               -  Hepatic: bilirubin ≤ 1.5 x the upper limit of normal (ULN), ALT and AST ≤ 3.0 x
                  ULN (or ≤ 5.0 x ULN in the presence of hepatic metastases)

               -  Renal: serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60
                  mL/min,

               -  Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% or ≥ the lower limit of
                  the institutional normal by echocardiogram (ECHO) or multiple gated acquisition
                  scan (MUGA);

        Exclusion Criteria:

          1. Has had major surgery within 30 days of starting study treatment.

          2. Has active CNS metastases. Subjects with neurological symptoms must undergo a head CT
             scan or brain MRI to exclude brain metastasis.

          3. Has a history of a prior malignancy with the exception of the following: adequately
             treated basal cell or squamous cell skin cancer, in situ cervical cancer, clinically
             localized prostate cancer treated with definitive local therapy and without evidence
             of recurrent disease and without the need for androgen deprivation therapy, or other
             cancer for which the subject has been disease-free for at least 5 years.

          4. Has had treatment with another anticancer agent or investigational agent within 30
             days prior to being registered for protocol therapy.

          5. Has had prior radiation therapy to > 25% of the bone marrow.

               -  NOTE: No radiation therapy within 30 days prior to being registered for protocol
                  therapy.

          6. Has a clinically significant infection as judged by the treating investigator.

          7. Pregnant or nursing females.

          8. Patients with known history of seropositive human immunodeficiency virus (HIV) or
             patients who are receiving immunosuppressive medications that would, in the opinion of
             the investigator, increase the risk of serious neutropenic complications.

          9. History of congestive heart failure

         10. History of recent myocardial infarction

         11. History of interstitial lung disease, pulmonary fibrosis or symptomatic pulmonary
             disease