Evaluation the Treatment of Tamoxifen of Low/Intermediate Risk Bladder Tumors (BCTamoxifen)

Phase II Trial of Estrogen Receptor Targeted Treatment of Non-Muscle Invasive Bladder Cancer With Tamoxifen.

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

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Tamoxifen Citrate

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Harris Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tamoxifen; 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.	Drug: Tamoxifen Citrate; Single-center, two-stage phase-II clinical trial (Simon design); Other Names: Nolvadex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Efficacy for Treatment of Low/Intermediate- Risk Bladder Tumors, Assessing for the Clinical Response of the Marker Lesion	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	2.5 years

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Guilherme Godoy, M.D., Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2015
• Primary Completion (ACTUAL): September 12, 2017
• Study Completion (ACTUAL): June 28, 2019

Study Registration Dates

• First Submitted: July 21, 2014
• First Submitted That Met QC Criteria: July 21, 2014
• First Posted (ESTIMATE): July 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): January 13, 2021
• Last Update Submitted That Met QC Criteria: December 18, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Bladder Cancer; Tamoxifen citrate
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: H-25233; K23CA160664 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO