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

• ClinicalTrials.gov Identifier: NCT06018116
• Recruitment Status: Withdrawn
• First Posted: August 30, 2023
• Last Update Posted: February 15, 2024
• Sponsor: CHU de Quebec-Universite Laval
• Collaborator: Cancer Research Society
• Information provided by (Responsible Party): CHU de Quebec-Universite Laval

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Urothelial Carcinoma	Drug: Bicalutamide 150 mg; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Canadian Phase II, Placebo-controlled Randomized Trial of Bicalutamide in Patients Receiving Maintenance Avelumab for Metastatic Urothelial Cancer.
• Actual Study Start Date: November 7, 2023
• Actual Primary Completion Date: January 31, 2024
• Actual Study Completion Date: February 12, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Rate of bladder tumor recurrence [ Time Frame: 30 months ]
   The primary outcome will be to the time to investigator-assessed progression on avelumab therapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Canada

CHU de Québec - Université Laval

Québec, Canada, G1G 5X1

Sponsors and Collaborators

CHU de Quebec-Universite Laval

Cancer Research Society

Investigators

• Study Chair: Paul Toren, MD, PhD, FRCSC; CHU de Québec - Université Laval

More Information

• Responsible Party: CHU de Quebec-Universite Laval
• ClinicalTrials.gov Identifier: NCT06018116
• Other Study ID Numbers: MP-20-2024-6963
• First Posted: August 30, 2023
• Last Update Posted: February 15, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by CHU de Quebec-Universite Laval:

bicalutamide; avelumab

Additional relevant MeSH terms:

Carcinoma, Transitional Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Avelumab; Bicalutamide; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Androgen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists