Clinical trial NCT00710970: Tamoxifen for Progressive Transitional Cell Carcinoma Following Previous Chemotherapy Treatment
Official title: H-16848 - Phase II Pilot Study With Correlative Markers of Tamoxifen for Progressive Transitional Cell Carcinoma Following Previous Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Keywords: Urinary Bladder Neoplasms
Previous Chemotherapy
Tamoxifen
Anti-tumor activity
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Cytogen Corporation
First posted: 2008-07-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Freedom From Progression of Cancer at 4 Months
timeFrame: Estimated from date of starting therapy until 4 months but up to progression or death which ever comes first.
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: Rome
country: Italy
facility: San Camillo and Forlanini Hospitals
Study officials:
affiliation: Baylor College of Medicine
name: Seth P. Lerner, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim HT, Kim BC, Kim IY, Mamura M, Seong DH, Jang JJ, Kim SJ. Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis through cleavage of BAD in TSU-PR1 human cancer cells. J Biol Chem. 2002 Sep 6;277(36):32510-5. doi: 10.1074/jbc.M202852200. Epub 2002 Jun 25.
citation: Shen SS, Smith CL, Hsieh JT, Yu J, Kim IY, Jian W, Sonpavde G, Ayala GE, Younes M, Lerner SP. Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer. 2006 Jun 15;106(12):2610-6. doi: 10.1002/cncr.21945.