Urinary Bladder Neoplasms
Conditions
Keywords
Urinary Bladder Neoplasms, Previous Chemotherapy, Tamoxifen, Anti-tumor activity
Brief 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.
Interventions
DRUGTamoxifen
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.
Sponsors
AstraZeneca
Cytogen Corporation
Seth Lerner
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Freedom From Progression of Cancer at 4 Months | Estimated from date of starting therapy until 4 months but up to progression or death which ever comes first. | Clinical Assessments were performed every 4 weeks and imaging every 8 weeks or earlier if indicated. Patients were followed every month for clinical symptoms and signs of progression. Patients underwent Radiographic CT scans every 8 weeks to look for progression. |
Countries
Italy, United States
Participant flow
Recruitment details
Patients presenting to the Scott Department of Urology for management of recurrent bladder cancer and fulfill the following criteria will be recruited.
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Receiving 20mg Tamoxifen Tamoxifen : 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. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Never took drug | 3 |
Baseline characteristics
| Characteristic | Single Arm Receiving 20mg Tamoxifen |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 69 years STANDARD_DEVIATION 10.844 |
| Region of Enrollment Italy | 7 participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 19 |
| serious Total, serious adverse events | 2 / 19 |
Outcome results
Primary
Number of Participants With Freedom From Progression of Cancer at 4 Months
Clinical Assessments were performed every 4 weeks and imaging every 8 weeks or earlier if indicated. Patients were followed every month for clinical symptoms and signs of progression. Patients underwent Radiographic CT scans every 8 weeks to look for progression.
Time frame: Estimated from date of starting therapy until 4 months but up to progression or death which ever comes first.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Receiving 25mg Tamoxifen | Number of Participants With Freedom From Progression of Cancer at 4 Months | 20 Participants |