Tamoxifen for Progressive Transitional Cell Carcinoma Following Previous Chemotherapy Treatment

NCT00710970 | Completed Phase 2 Results DMC

• 1 other identifier: H-16848
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 2

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.

Conditions

Urinary Bladder Neoplasms

Keywords

Urinary Bladder Neoplasms; Previous Chemotherapy; Tamoxifen; Anti-tumor activity

Outcome Measures

Primary Outcomes (1)

• 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.

  Estimated from date of starting therapy until 4 months but up to progression or death which ever comes first.

Study Arms (1)

Single Arm Receiving 25mg Tamoxifen

EXPERIMENTAL

Drug: Tamoxifen

Interventions

Tamoxifen DRUG

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.

Also known as: raloxifene

Single Arm Receiving 25mg Tamoxifen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Seth Lerner: lead
• AstraZeneca: collaborator
• Cytogen Corporation: collaborator

Study Sites (2)

Baylor College Of Medicine

Houston, Texas, 77030, United States

Location

San Camillo and Forlanini Hospitals

Rome, Italy

Location

Related Publications (2)

• 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.

  PMID: 12084714 BACKGROUND

• 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.

  PMID: 16700038 BACKGROUND

Related Links

• Baylor College of Medicine's Clinical Trials
• Scott Department of Urology, Baylor College of Medicine
• Bladder Cancer Advocacy Network

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Tamoxifen; Raloxifene Hydrochloride

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Seth P. Lerner, M.D., F. A. C. S.
• Organization: Baylor College of Medicine

slerner@bcm.edu

713-798-6841

Study Officials

• Seth P. Lerner, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 7, 2008
• First Posted: July 8, 2008
• Study Start: January 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2012
• Last Updated: January 24, 2022
• Results First Posted: August 22, 2013

Record last verified: 2022-01

Locations

US (1); IT (1)