Nab-paclitaxel Plus Gemcitabine as First-line Therapy for Cisplatin-ineligible or Cisplatin-incurable Advanced Urothelial Carcinoma
Condition: Urothelial Carcinoma; Bladder Cancer; Transitional Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: nab-paclitaxel; Gemcitabine
Intervention description: Induction: 125 mg/m² by intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle for 3 to 6 cycles to be given with Gemcitabine.
Maintenance: single agent nab-paclitaxel (260 mg/m²) by IV infusion every 21 days) until disease progression, intolerable toxicity or patient decision to discontinue treatment.; Induction: 1000 mg/m²) by IV infusion on Days 1 and 8 of each 21-day cycle for 3 to 6 cycles.
Intervention MeSH terms: Paclitaxel; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: nab-paclitaxel; gemcitabine

Summary:

      The purpose of this trial is to determine the benefit of the combination of nab-paclitaxel
      plus gemcitabine given for 6 cycles, followed by maintenance nab-paclitaxel alone, in
      patients with cisplatin-ineligible or cisplatin-incurable advanced urothelial carcinoma (UC).
    

Eligibility criteria:

        KEY POINTS:

        Inclusion Criteria:

          1. Histologically confirmed diagnosis of urothelial carcinoma (UC) that is either
             metastatic (any N+ M1) or locally advanced and unresectable (T4bN0). A component of
             urothelial (transitional cell) carcinoma is required.

          2. Two groups of patients are eligible:

               1. Poor candidates for cisplatin-based chemotherapy based on the presence of ≥ 1 the
                  following:

                    -  Glomerular filtration rate of 30-60 ml/min (Cockcroft-Gault formula)

                    -  ECOG performance status score of 2

                    -  Hearing loss (trouble communicating with hearing aids or hearing loss at ≤ 3
                       KHz)

                    -  Grade ≥3 heart failure

                    -  Age ≥80 years

                    -  Other concurrent illness which may make the patient a poor candidate for
                       receiving cisplatin.

                  Note: Enrollment of patients with 2 or more of these criteria should occur only
                  after careful consideration by the treating physician regarding the patient's
                  ability to tolerate combination chemotherapy.

                  OR

               2. Poor prognosis and defined as cisplatin-incurable due to the presence of
                  metastasis to at least one visceral site (these patients are not required to have
                  any of the cisplatin-ineligibility criteria).

                    -  ECOG performance status score of 0, 1, or 2.

          3. Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors
             (RECIST) version 1.1.

          4. Patients with brain metastases are allowed if treatment was completed at least 4 weeks
             prior to study treatment, neurologic symptoms are minimal and stable during the
             preceding 4 weeks, and maintenance dexamethasone is not required.

          5. Adequate hematologic, liver and kidney function.

          6. Willingness and ability to comply with study requirements and give written informed
             consent.

        Exclusion Criteria:

          1. Previous systemic chemotherapy for UC with the exception of perioperative (neoadjuvant
             or adjuvant) treatment or treatment with concurrent chemoradiation for locally
             advanced disease. All of these treatments must have been completed more than 1 year
             previously.

          2. Presence of small-cell or sarcomatoid component in tumor histology.

          3. Women who are pregnant or breast-feeding.

          4. Major surgical procedures ≤28 days of beginning study drug, or minor surgical
             procedures ≤7 days. No waiting required following port-a-cath placement.

          5. Cardiac diseases currently or within the last 6 months:

          6. Inadequately controlled hypertension.

          7. Currently receiving treatment with therapeutic doses of warfarin sodium. (A maximum
             daily dose of 1 mg will be permitted for port line patency. Low molecular weight
             heparin is allowed.)

          8. Serious active infection at the time of treatment, or another serious underlying
             medical condition that would impair the ability of the patient to receive protocol
             treatment.

          9. Known diagnosis of human immunodeficiency virus, hepatitis B or hepatitis C (screening
             for these diseases is not required.).

         10. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years
             previously. Patients with Stage I cancer who have received definitive local treatment
             and are considered unlikely to recur are eligible. All patients with previously
             treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with
             history of non-melanoma skin cancer.