Tamoxifen for Progressive Transitional Cell Carcinoma Following Previous Chemotherapy Treatment
Condition: Urinary Bladder Neoplasms
MeSH terms: Carcinoma, Transitional Cell; Urinary Bladder Neoplasms
Intervention: Tamoxifen
Intervention description: Tamoxifen is administered at 20 mg/day as a single daily oral dose. Tamoxifen is continued until progressive disease or intolerable grade 3 or 4 side effects occur due to tamoxifen.
Intervention MeSH terms: Tamoxifen; Raloxifene Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urinary Bladder Neoplasms; Previous Chemotherapy; Tamoxifen; Anti-tumor activity

Summary:

      The major objective of this two-stage phase II study is to determine whether tamoxifen is
      deserving of further study in metastatic bladder cancer. Tamoxifen is expected to function as
      a cytostatic (and not cytotoxic) agent, and may produce more disease stability than
      regression. Sustained stable disease is considered to be clinically important and the more
      likely event. Hence, 4-month freedom from progression is chosen as the primary end-point
      instead of response rate. Freedom from progression is defined as the period from start of
      therapy to the time of objective radiologic progression. A total of 25 subjects will be
      enrolled, 15 during stage 1 and 10 during stage 2 of a two-stage minimax design phase II
      study.

      Pre-therapy evaluation (within 3 weeks of initiation of therapy):

        -  History and physical examination (H and P)

        -  Performance status (PS) assessment

        -  CBC (complete blood counts)

        -  CMP (complete metabolic profile)

        -  Pregnancy test (in women younger than 50)

        -  Computed tomography (CT) scan of the chest, abdomen and pelvis

        -  Bone scan if bone pain or raised alkaline phosphatase

        -  Biopsy (may use previous biopsy specimen)

        -  Samples of plasma from the routine CBC and CMP will be banked indefinitely for future
           biomarker studies at the Scott Department of Urology.

      Treatment plan: Therapy will be administered as an outpatient. Tamoxifen is administered at
      20 mg/day as a single daily oral dose. Clinical assessment of patients by a history and
      physical examination will be performed every 4 weeks (one cycle). Objective radiological
      assessment of response will be made every 8 weeks or earlier if clinically indicated. A CT
      (computerized tomography) scan of the abdomen, pelvis and chest will be performed at baseline
      and every 2 cycles. A response is confirmed by repeating the scans in 4 weeks. Bone scan is
      performed if the patient complains of new bone pain or has raised alkaline phosphatase. A
      radiologist who is blinded to the treatment regimen reads the scans. The RECIST criteria are
      used to define response. Tamoxifen is continued until progressive disease or intolerable side
      effects occur.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients previously diagnosed with bladder cancer who have already received 1-2
             systemic therapy regimens (chemotherapy or biological therapy or both) but including
             at least one chemotherapy regimen.

          -  Patients who have had the cancer spread to other parts of the body.

          -  Patients must have adequate liver function.

        Exclusion Criteria:

          -  Patients who have uncontrolled nervous system metastasis

          -  Patients who are pregnant

          -  Patients who have had systemic therapies within the past 4 weeks

          -  Patients who plan to have major surgery within 2 weeks

          -  Patients who have Grade III/IV heart problems

          -  Patients who have severe and/or uncontrolled medical disease.

          -  Patients who might be at high risk for deep vein thrombosis