A Canadian Trial of Bicalutamide in Patients Receiving Maintenance Avelumab for Metastatic Urothelial Cancer.

NCT ID: NCT06018116

Last Updated: 2024-02-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-07
• Study Completion Date: 2024-02-12

Brief Summary

This is a Phase II, multi-center, placebo-controlled randomized controlled trial of standard of care (SOC) avelumab versus SOC avelumab with bicalutamide for patients with metastatic or locally advanced urothelial carcinoma.

Detailed Description

Urothelial carcinoma (UC) is the second most common urological cancer after prostate cancer. Non-muscle invasive bladder cancer (NMIBC) is the most common form (~75%). Muscle-invasive bladder cancer (MIBC) is found at presentation in ~25% of patients, with 10-20% of NMIBC eventually becoming MIBC. Risk groups for NMIBC are based on number of tumours, stage and size. Almost half of patients with MIBC eventually progress to metastatic disease.

Treatments for metastatic urothelial carcinoma (mUC) have evolved rapidly over the last several years. Pembrolizumab demonstrated benefit as second line therapy for locally advanced and metastatic UC. Subsequently, the landmark Phase III randomized JAVELIN trial showed that the addition of avelumab as maintenance therapy following a response to chemotherapy for mUC significantly prolonged overall survival relative to best supportive care (hazard ratio (HR) = 0.69; 95% confidence interval (CI), 0.56-0.86; P = 0.001). Overall survival and progression-free survival were 21.4 months (18.9 to 26.1) and 5.5 (4.2 to 7.2) months, respectively. This trial established avelumab as the SOC treatment and initial immunotherapy for mUC following chemotherapy.

The investigators have selected a double-blind placebo-controlled randomized study design to be able to assess the pragmatic endpoint of investigator-assessed clinical progression. Randomization will assign patients 2:1 to bicalutamide 150mg daily plus SOC avelumab or placebo plus SOC avelumab. Patients will be followed every 3 months after avelumab treatment has started and until progression.

Conditions

Metastatic Urothelial Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Bicalutamide

standard of care (SOC) avelumab with 150mg daily oral bicalutamide

Group Type: EXPERIMENTAL

Bicalutamide 150 mg

Intervention Type: DRUG

nonsteroidal antiandrogen

Placebo

standard of care (SOC) avelumab with daily oral placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo

Interventions

Bicalutamide 150 mg

nonsteroidal antiandrogen

Intervention Type: DRUG

Placebo

placebo

Intervention Type: DRUG

Other Intervention Names

standard of care avelumab; standard of care avelumab

Eligibility Criteria

Inclusion Criteria

1. Age 18 or greater and able to provide informed consent for the trial;

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening;

3. Patients with histologically confirmed urothelial carcinoma;

4. Patients is a candidate for a course of maintenance avelumab treatment for metastatic or locally advanced urothelial carcinoma;

5. Male patients with partners of child-bearing potential must agree to 2 acceptable forms of birth control and be continued for at least 130 days after study drug is discontinued.

Exclusion Criteria

1. 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.

2. Patients with neutrophils (< 1,000/μL) will be ineligible.

3. Patients on androgen replacement therapy, or those with prostate cancer or other diseases currently treated with systemic hormonal therapy will be ineligible for study enrollment. Patients receiving 5-alpha reductase inhibitors will not be excluded.

4. Patients who have a concurrent malignancy other than UC within the past years for which treatment is planned within the next 6 months.

5. Patients taking an investigational drug within 2 weeks of enrollment into this study.

6. Patients receiving or planning to receive coumadin therapy.

7. Female patients with childbearing potential are excluded due to known teratogenic effects of bicalutamide.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research Society

OTHER

Sponsor Role: collaborator

CHU de Quebec-Universite Laval

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Toren, MD, PhD, FRCSC

Role: STUDY_CHAIR

CHU de Québec - Université Laval

Locations

CHU de Québec - Université Laval

Québec, , Canada

Countries

Canada

Other Identifiers

MP-20-2024-6963

Identifier Type: -

Identifier Source: org_study_id