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Ethacrynic Acid Elimination in Non-Muscle Invasive Bladder Cancer Patients Undergoing Transurethral Resection

Phase 1
Completed
Conditions
Bladder Cancer
Interventions
Registration Number
NCT02852564
Lead Sponsor
Eugene Lee, MD
Brief Summary

Phase 1 study to provide quantitative characterization of the renal elimination of ethacrynic acid and metabolites in patients with non-muscle invasive bladder cancer (NMIBC) at the time of transurethral resection of bladder tumor

Detailed Description

Bladder cancer continues to be a significant healthcare and financial liability in the United States. Patients with Non-Muscle Invasive Bladder Cancer (NMIBC) are in desperate need for both effective and easily tolerated treatment options. Current standard of care includes immediate post-operative Mitomycin C (MMC), which decreases the rate of recurrence but does not alter progression. Furthermore, in patients with high-grade NMIBC, standard of care dictates that patients undergo intravesical Bacillus Calmette-Guerin (BCG) therapy. This treatment has a high degree of morbidity with both local and systemic side effects along with significant discomfort from treatment (intra-urethral catheterization and bladder instillation). Our goal is to develop a bladder cancer treatment strategy designed to decrease recurrence/progression rates in addition to decreasing the morbidity of treatment.

Twelve evaluable NMIBC patients will participate in this Phase 1 trial.

Treatment - patients will receive a single, 50 mg oral dose of ethacrynic acid administered as two 25 mg strength EDECRIN® tablets immediately prior to transurethral resection of bladder tumor.

Concentrations and excretion rates of ethacrynic acid in the urine, as well as of cysteine, glutathione, and mercapturate metabolites, will be measured for each of 4 urine specimens collected on the day of surgery (before, during, and at 2 timepoints after surgery).

Adverse events, serious adverse events, laboratory values, and vital sign measurements will be collected.

Efficacy of ethacrynic acid treatment will be estimated by recording recurrence/non-recurrence of disease at 3 months post-treatment

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Enrolled ParticipantsEthacrynic AcidAdministration of a single, 50 mg oral dose of ethacrynic acid prior to bladder tumor removal surgery (Transurethral Resection of Bladder Tumor \[TURBT\])
Primary Outcome Measures
NameTimeMethod
Urine Concentration - Ethacrynic Acid and its conjugates4 hours after surgery

Concentration of Ethacrynic acid and its conjugates in urine at 4 hours after surgery. A: Ethacrynic acid concentration (ng/mL) B: Glutathione (ng/mL) C: Cysteine (ng/mL) D: Mercapturic acid (ng/mL) will be measured.

Excretion Rates - Ethacrynic Acid and its conjugates4 hours after surgery

Urinary excretion rates of ethacrynic acid and its conjugates 4 hours after surgery.

A: Ethacrynic acid concentration (ng) B: Glutathione (ng) C: Cysteine (ng) D: Mercapturic acid (ng) will be measured.

Secondary Outcome Measures
NameTimeMethod
Number of Participants with Tumor Recurrence / Non-Recurrence using RECIST version 1.190 days after surgery

Tumor Recurrence / Non-Recurrence will be measured using RECIST version 1.1 to assess efficacy of ethacrynic acid

Number of Participants with treatment-related adverse events as assessed by CTCAE 4.03During and after surgery, up to 3 months following surgery

Adverse events / toxicity related to Ethacrynic Acid as reported by participants will be recorded. Toxicity will be measured via analysis of patient adverse events (physiological parameter). Adverse events will be scored using NCI Common Toxicity Criteria for Adverse Events v 4.0.3 (June 14,2010).

Trial Locations

Locations (1)

The University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

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