A Canadian Trial of Bicalutamide in Patients Receiving Maintenance Avelumab for Metastatic Urothelial Cancer. (CANUCK-01)

A Canadian Phase II, Placebo-controlled Randomized Trial of Bicalutamide in Patients Receiving Maintenance Avelumab for Metastatic Urothelial Cancer.

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Urothelial Carcinoma
• Intervention / Treatment: Drug: Placebo; Drug: Bicalutamide 150 mg

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1G 5X1
    • CHU de Québec - Université Laval

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bicalutamide; standard of care (SOC) avelumab with 150mg daily oral bicalutamide	Drug: Bicalutamide 150 mg; nonsteroidal antiandrogen; Other Names: standard of care avelumab
Placebo Comparator: Placebo; standard of care (SOC) avelumab with daily oral placebo	Drug: Placebo; placebo; Other Names: standard of care avelumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of bladder tumor recurrence	The primary outcome will be to the time to investigator-assessed progression on avelumab therapy.	30 months

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Collaborators: Cancer Research Society
• Investigators: Study Chair: Paul Toren, MD, PhD, FRCSC, CHU de Québec - Université Laval

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2023
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): February 12, 2024

Study Registration Dates

• First Submitted: August 25, 2023
• First Submitted That Met QC Criteria: August 25, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: bicalutamide; avelumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Hormone Antagonists; Androgen Antagonists; Avelumab; Antibodies, Monoclonal; Bicalutamide
• Other Study ID Numbers: MP-20-2024-6963

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes