A Phase II Trial of Bicalutamide in Patients Receiving Intravesical BCG for Non-muscle Invasive Bladder Cancer

Study Overview
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Brief Summary
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This is a phase II randomized controlled clinical trial comparing standard induction BCG versus bicalutamide and standard induction BCG among patients with non-muscle invasive bladder cancer.

Detailed Description
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Bladder cancer is the second most common urological cancer after prostate cancer. Non-muscle invasive bladder cancer (NIMBC) is the most common form (  75%). The standard treatment involves the use of intravesical instillation of bacillus Calmette-Guérin (BCG). Nonetheless, 30-40% of the patients still relapse or progress. Clinical and laboratory research suggests that medications targeting the androgen receptor, such as bicalutamide, combined with the standard treatment with BCG may decrease the recurrence rate of NMIBC. The participants will be randomized to either the treatment with 1) daily intake of 150 mg bicalutamide for 3 months overlapping with the 6 cycles of intravesical instillations of BCG or 2) the standard of care of 6 cycles of intravesical instillation BCG . The participation to this this trial should last 36 months from the screening visit to the last follow-up visit.

Official Title
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A Phase II Randomized Trial of Bicalutamide in Patients Receiving Intravesical BCG for Non-muscle Invasive Bladder Cancer

Conditions
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Non-Muscle Invasive Bladder Cancer

Intervention / Treatment
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* Drug: Bicalutamide
* Biological: Control Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males, age 18 or greater. Patients with histologically confirmed non-muscle invasive urothelial carcinoma. Patients have been recommended for a course of intravesical BCG induction treatment by their urologist Patients who received gemcitabine, epirubicin or mitomycin C instillations immediately post-operatively will be eligible for enrollment. Patients with partners of child-bearing potential must agree to 2 acceptable forms of birth control and be continued for at least 3 months after study drug is discontinued. Exclusion Criteria: Patients who have received induction BCG therapy within the last 5 years will be ineligible for enrollment. Patients who have received an induction course of intravesical chemotherapy within the last 5 years will be ineligible for enrollment. Patients with a history of myocardial infarction or hospital admission for heart failure within the previous 12 months or who have unstable cardiovascular status will be ineligible for enrollment. Patients who have uncontrolled hypertension (for our purposes, defined as those having a systolic blood pressure > 160 documented on 2 occasions despite appropriate medical therapy) will similarly be ineligible. Patients with a history of venous thrombo-embolism (DVT/PE) within the past 3 years. 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. Patients with kidney disease with an estimated glomerular filtration rate (eGFR) < 30 will be ineligible. Patients with neutropenia (< 3,000/μL) will be ineligible. 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 will not be excluded. Patients who have undergone treatment for any malignancy other than bladder cancer within the past 2 years except for superficial non-melanoma skin cancers. Patients with prior history of prostate cancer treated by definitive local therapy > 5 years ago will only be eligible if they have had no clinical or biochemical evidence of recurrent prostate cancer. Patients taking an investigational drug within 3 weeks of enrollment into this study. Patients receiving or planning to receive coumadin therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bicalutamide<br>Induction intravesical Bacille Calmette-Guérin treatment with 150 mg daily oral bicalutamide for 90 days | Drug: Bicalutamide<br>* Induction intravesical BCG with bicalutamide 150 mg for 90 days<br>* Other names: Nonsteroidal antiandrogen;|
| Active Comparator: Control Arm<br>Induction intravesical Bacille Calmette-Guérin treatment | Biological: Control Arm<br>* Induction BCG<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of bladder tumour recurrence | To time to bladder tumor recurrence compared to the standard of care induction BCG | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of tumour progression | To compare the incidence of tumor progression between the intervention and control arms | 3 years | 
| Number of tumor recurrences | To compare the overall incidence of tumor recurrences between intervention and control arms | 3 years | 
| Number of tumours at first recurrence | Evaluation of the number of tumours at first recurrence between the two arms | 3 years | 
| Quality of life (QLQ-C30) | Evaluation of quality of life with QLQ-C30 questionnaire (EORTC Core Quality of Life questionnaire). The scale scores range from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptom | 3 years | 
| Evaluation of urinary symptoms | Evaluation of urinary symptoms with International Prostate Symptom Score (IPSS) . questionnaire. The total score can range from 0 to 35 (0 being asymptomatic and 35 being very symptomatic). | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bicalutamide, BCG instillation