Evaluation the Treatment of Tamoxifen of Low/Intermediate Risk Bladder Tumors

Phase 2

Completed

• Conditions: Bladder Cancer
• Interventions: Drug: Tamoxifen Citrate

• Registration Number: NCT02197897
• Lead Sponsor: Baylor College of Medicine

Brief Summary

Evaluate the treatment of tamoxifen of low/intermediate-risk bladder tumors

Detailed Description

Patients with primary or recurrent low/intermediate-risk papillary urothelial carcinoma of the bladder will undergo resection of all but one marker lesion, measuring at least 6mm but no greater than 10mm, and biopsy of normal-appearing mucosa. Patients with a solitary tumor will undergo only biopsy prior to treatment. A 2mm cold cup biopsy of the marker lesion will always be performed to rule out a potential high-grade lesion and for assessment of pretreatment immunohistochemistry expression levels of ERα, ERβ1, Ki-67 (proliferation marker) and TUNEL (apoptosis marker). If there are multiple tumors, all lesions, except the marker lesion will be resected and sent for analysis. These patients will not receive single immediate post-operative intravesical instillation of mitomycin-C. They will then undergo a 12-week course of treatment with tamoxifen administered as a single daily oral dose of 20mg. At the completion of therapy, patients will undergo resection of the marker lesion (or biopsy of the tumor bed, if a complete response is observed) and biopsy of normal-appearing bladder mucosa again. Toxicity evaluations will be performed at the beginning (day 3), midway (week 6), and at completion of treatment (week 12), prior to resection of the marker lesion. A final assessment for toxicity will also be performed 30 days after completion of therapy as well as a second definitive resection of the marker lesion. Urine samples will be obtained with the index tumor in place (marker lesion), and after completion of treatment, at the time of definitive transurethral resection of the index tumor, as part of the standard clinical care of these patients, and at the discretion of the surgeon for assessment of urinary cytology. The urine samples will not be utilized for the research study. All normal-appearing bladder biopsies (pre and post-treatment), the additional tumors (in case of multiple lesions), and the definitive resection of the marker lesion (in the absence of response to therapy) will provide sufficient material for immunohistochemistry assessment of the expression levels of ERα, ERβ-1, ERβ-2, ERβ-5, Ki-67, and TUNEL, and also for RT-qPCR for mRNA analyses of ERα, ERβ-1, ERβ-2, and ERβ-5. The pretreatment biopsy of the marker lesion will be performed with a smaller biopsy forceps and will provide limited material, sufficient only for immunohistochemistry assessment of the expression levels of ERα, ERβ-1, Ki-67, and TUNEL.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-07-21
• Study First Submitted QC: 2014-07-21
• Study First Posted: 2014-07-23
• Study Start: 2015-04-01
• Primary Completion: 2017-09-12
• Study Completion: 2019-06-28
• Results First Submitted: 2020-07-21
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-18
• Last Update Submitted: 2020-12-18
• Results First Posted: 2021-01-13
• Last Update Posted: 2021-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Males and females age 21 or older. Histologic evidence of urothelial carcinoma of the bladder. Low/Intermediate-risk papillary urothelial carcinoma of the bladder, at initial occurrence or recurrent with >6 months interval free of disease.

Patients with multifocal tumors must have resectable lesions. Patients may be treatment-naïve or have failed 1 previous regimen of intravesical therapy.

At least one endoscopically measurable tumor 6 - 10mm in diameter. Adequate hepatic and renal function. Patient or authorized proxy needs to have signed the informed consent form.

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Exclusion Criteria

Patients with sessile appearing tumors, which may be invasive or high-grade. Diagnosis of urothelial carcinoma involving the prostatic urethra or upper urinary tract.

Plans for pelvic radiation while participating in the study. Concurrent use of warfarin, heparin, or chronic use of NSAIDs, including aspirin (other than cardioprotective doses of 80mg daily) within 30 days prior to registration or during the trial.

Concurrent use of selective serotonin reuptake inhibitors or aromatase inhibitors.

Chronic or acute renal or hepatic disorder or any other condition, medical or psychological that, in the opinion of the investigator, could jeopardize the subject's safe participation.

Any other investigational drug within 30 days prior to registration and during the study.

Women Exclusion Pregnant or lactating women. Personal history of endometrial cancer or any abnormal uterine bleeding. Previous or concurrent treatment with SERM and/or hormonal replacement therapy within 3 months of the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tamoxifen	Tamoxifen Citrate	As a single-arm study (single group assignment), Tamoxifen citrate will be given to all patients at a 20mg/day dose for 12 weeks using a marker-lesion study design.

Primary Outcome Measures

Name	Time	Method
Evaluate the Efficacy for Treatment of Low/Intermediate- Risk Bladder Tumors, Assessing for the Clinical Response of the Marker Lesion	2.5 years	Evaluate the efficacy of tamoxifen for treatment of low/intermediate-risk bladder tumors, utilizing the RECIST criteria combined with the final biopsy of the marker lesion or the bed of the lesion in case of a complete response

Trial Locations

Locations (2)

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Harris Health System; 🇺🇸 Houston, Texas, United States