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

NCT02852564 | Completed Phase 1 DMC

• 1 other identifier: 2015IITEthacrynicAcidBladderCa
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Conditions

Bladder Cancer

Keywords

Non-Muscle; Invasive; Bladder; Cancer; Muscle; Surgery; Transurethral; Resection; Tumor; Ethacrynic; Acid; Mitomycin; Urine; NMIBC

Outcome Measures

Primary Outcomes (8)

• Urine Concentration - Ethacrynic Acid and its conjugates

  Concentration of Ethacrynic acid and its conjugates in urine for baseline at 30 minutes before surgery. A: Ethacrynic acid concentration (ng/mL) B: Glutathione (ng/mL) C: Cysteine (ng/mL) D: Mercapturic acid (ng/mL) will be measured.

  Baseline at 30 minutes before surgery

• Urine Concentration - Ethacrynic Acid and its conjugates

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

  During surgery

• Urine Concentration - Ethacrynic Acid and its conjugates

  Concentration of Ethacrynic acid and its conjugates in urine at 2 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.

  2 hours after surgery

• Urine Concentration - Ethacrynic Acid and its conjugates

  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.

  4 hours after surgery

• Excretion Rates - Ethacrynic Acid and its conjugates

  Urinary excretion rates of ethacrynic acid and its conjugates for baseline at 30 minutes before surgery. A: Ethacrynic acid concentration (ng) B: Glutathione (ng) C: Cysteine (ng) D: Mercapturic acid (ng) will be measured.

  30 minutes before surgery

• Excretion Rates - Ethacrynic Acid and its conjugates

  Urinary excretion rates of ethacrynic acid and its conjugates during surgery. A: Ethacrynic acid concentration (ng) B: Glutathione (ng) C: Cysteine (ng) D: Mercapturic acid (ng) will be measured.

  during surgery

• Excretion Rates - Ethacrynic Acid and its conjugates

  Urinary excretion rates of ethacrynic acid and its conjugates 2 hours after surgery. A: Ethacrynic acid concentration (ng) B: Glutathione (ng) C: Cysteine (ng) D: Mercapturic acid (ng) will be measured.

  2 hours after surgery

• Excretion Rates - Ethacrynic Acid and its conjugates

  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.

  4 hours after surgery

Secondary Outcomes (2)

• Number of Participants with treatment-related adverse events as assessed by CTCAE 4.03

  During and after surgery, up to 3 months following surgery

• Number of Participants with Tumor Recurrence / Non-Recurrence using RECIST version 1.1

  90 days after surgery

Study Arms (1)

Enrolled Participants

EXPERIMENTAL

Administration of a single, 50 mg oral dose of ethacrynic acid prior to bladder tumor removal surgery (Transurethral Resection of Bladder Tumor \[TURBT\])

Drug: Ethacrynic Acid

Interventions

Ethacrynic Acid DRUG

One oral dose at 50 mg prior to bladder tumor removal surgery

Also known as: Edecrin

Enrolled Participants

Eligibility Criteria

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

You may qualify if:

• NOTE: Both patients who will and will not receive standard of care concomitant mitomycin C are eligible to enroll in this study.
• Ability to understand and the willingness to sign a written informed consent
• Diagnosis of presumed non-muscle invasive bladder cancer based on office based cystoscopy (primary or recurrent), and planned transurethral resection of bladder tumor (TURBT)
• Participants must have tumors with anticipated transurethral resection time ≤ 1 hour
• Previous history of intravesical therapy allowed
• Age ≥ 18 years
• Performance Status 0-1
• Adequate organ and marrow function as defined below:
• leukocytes ≥ 3,000/mcL
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 100,000/mcl
• total bilirubin within normal institutional limits
• Aspartate Aminotransferase (AST) ≤ 2.5 X institutional upper limit of normal
• Alanine Aminotransferase (ALT) ≤ 2.5 X institutional upper limit of normal
• creatinine ≤ 2.5 X institutional upper limit of normal

You may not qualify if:

• Current or anticipated use of other investigational agents.
• Patient has known nodal or distant metastatic disease. Patients with nodal or metastatic disease require systemic chemotherapy. Furthermore, they should be excluded from this clinical trial because of their poor overall prognosis.
• Patients with locally advanced bladder cancer based on cross-sectional imaging (suspicion of extravesical disease or hydronephrosis)
• Patients with tumors with anticipated transurethral resection time greater than 1 hour
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ethacrynic acid or other agents used in study.
• Systolic blood pressure \< 90 mmHg and/or diastolic blood pressure \< 50 mmHg
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.

Sponsors & Collaborators

• Eugene Lee, MD: lead
• University of Kansas Medical Center: collaborator

Study Sites (1)

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplasms; Heartburn; Non-Muscle Invasive Bladder Neoplasms

Interventions

Ethacrynic Acid

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Phenoxyacetates; Glycolates; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids

Study Officials

• Eugene K Lee, MD

  The University of Kansas - Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: August 2, 2016
• Study Start: August 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

US (1)