A Phase II Prospective Single-arm Study of Dutasteride in Patients With Low-grade Non-muscle Invasive Bladder Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 95
- Locations
- 1
- Primary Endpoint
- Incidence of NMIBC recurrences in patients treated with dutasteride
Study Overview
Brief Summary
Low-grade non-muscle-invasive bladder cancer often comes back after treatment, requiring repeated surgeries, especially in older patients. These recurrences can cause complications, reduce quality of life, and increase healthcare costs. Currently, there is no well-tolerated preventive treatment routinely used for this low-risk disease.
This study will evaluate whether dutasteride, an oral medication that blocks androgen activity, can reduce the risk of bladder cancer recurrence. Dutasteride is generally well tolerated and easy to take. The study will also assess its safety in women.
The goal of this study is to determine whether dutasteride can provide a simple and effective way to prevent recurrences of low-grade non-muscle-invasive bladder cancer.
Detailed Description
The study will therefore include two separate cohorts of men (n=70) and women (n=25).
After the screening phase, eligible male and female patients who provide informed consent will receive dutasteride at a dose of 0.5 mg once daily for the duration of the study. All participants will follow the same treatment regimen.
Treatment will be continued until tumor recurrence or for up to two years in the absence of recurrence. In the event of tumor recurrence, patients will be offered the option to continue dutasteride treatment for a total duration of up to two years. The decision to continue or discontinue treatment, as well as the reasons for this decision, will be documented.
Regarding analyses, the male cohort is designed to provide the first prospective data on efficacy by comparison with a historical control cohort, while also collecting adherence and safety data specific to men with low-grade NMIBC.
The parallel female cohort is primarily intended to assess feasibility of recruitment and safety. In the published literature and our own institutional data, women represent approximately 25% of patients with low-grade NMIBC. Recruitment of female patients is therefore more challenging, compounded in part by the limited safety data available and the absence of demonstrated urinary benefits. Consequently, this cohort aims to determine whether inclusion of women in a subsequent phase 3 study will be feasible and safe.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients aged 18 or greater;
- •Patients with histologically confirmed low grade non-muscle invasive urothelial carcinoma. Patients with any mix of low- and high-grade urothelial carcinoma remain eligible given the frequent histological heterogeneity and the presence of a low grade component;
- •Patients have not been recommended for a course of intravesical BCG or chemotherapy induction treatment by their urologist;
- •Male patients with partners of child-bearing potential must agree to 2 acceptable forms of birth control and be continued for at least 6 months after study drug is discontinued.
Exclusion Criteria
- •Patients who are scheduled to receive BCG therapy or have received BCG therapy within the last 5 years will be ineligible for enrollment.
- •Patients who are scheduled to receive intravesical chemotherapy or have received an induction course of intravesical chemotherapy within the last 5 years will be ineligible for enrollment. Patients who received a single, post-operative (<24h) intravesical chemotherapy (e.g. gemcitabine, epirubicin or mitomycin C) dose are eligible.
- •Patients with clinical hypogonadism, those on androgen replacement therapy, or those with prostate cancer or other diseases treated with various forms of hormonal therapy will be ineligible for study enrollment.
- •Patients receiving 5-alpha-reductase inhibitors within the last 2 years are ineligible for enrollment.
- •Patients with a history of allergy or severe adverse reaction to finasteride or dutasteride are ineligible for enrollment.
- •Patients with a history of liver disease whose hepatic enzymes, alkaline phosphatase or bilirubin are greater than twice the upper limit of normal will be ineligible. Nonetheless, patients with Gilbert's disease may be accepted in the study.
- •Patients with multiple hospital admissions for heart failure within the previous 12 months or who have unstable cardiovascular status will be ineligible for enrolment.
- •Female patients with child-bearing potential are ineligible for enrollment, which is defined as any female under 50 years of age. Exceptions to this age limit may be permitted on a case-by-case basis by the Principal Investigator, based on documented confirmation that there is no child-bearing potential (such as a female without a uterus).
- •Patients receiving chronic treatment with potent CYP3A4 inhibitors, including but not limited to ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, troleandomycine, or ciprofloxacin, are ineligible for participation in the study. Occasional use of CYP3A4 inhibitors such as ciprofloxacin for an infection is not prohibited.
Arms & Interventions
Dutasteride 0.5 mg oral treatment daily
Participants will receive dutasteride 0.5 mg orally once daily for up to 2 years, or until tumor recurrence. Treatment may be continued after recurrence up to 2 years total, if the patient chooses to continue.
Intervention: Dutasteride (0.5mg) (Drug)
Outcomes
Primary Outcomes
Incidence of NMIBC recurrences in patients treated with dutasteride
Time Frame: From enrolment until first recurrence or 4 years of extended follow-up, whichever occurs first
To facilitate historical comparisons, a pathologic definition of recurrence is selected. Thus, investigators will be mandated to perform confirmatory biopsies or surgical resection of recurrences. For the female population, recruitment will be compared to the male population based on the established 1:3 ratio of female to male patients.
Secondary Outcomes
- Time to surgery(From enrolment until surgery for suspected recurrence of bladder cancer or 4 years of extended follow-up, whichever occurs first)
- Incidence of tumour progression(From enrolment until first progression or 4 years of extended follow-up, whichever occurs first)
- Number of tumour recurrences:(From enrolment until first recurrence or 4 years of extended follow-up, whichever occurs first)
- Number of tumours at recurrence(From enrolment until first recurrence or 4 years of extended follow-up, whichever occurs first)
- Concordance of cystoscopic recurrence with pathologic recurrence(From enrolment until 4 years of extended follow-up, whichever occurs first)
- Quality of life assessed by the European Organisation for Research and Treatment of Cancer(EORTC) Quality of Life Questionnaire (QLQ) non-muscle invasive bladder cancer questionnaire(NMIBC) module 24(From enrolment to 24 months (end of treatment))
- Urinary symptoms assessed by Bladder Utility Symptom Score (BUSS)(From enrollment until 2 years (end of treatment))
- Urinary symptoms assessed by the Internation Prostate Symptom Score (IPSS) questionnaire(From enrollment until 2 years (end of treatment))
Investigators
Paul Toren
Principal Investigator
CHU de Quebec-Universite Laval