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
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.
- 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.
- 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