Durvalumab and Vicineum in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With Bacillus Calmette-Guerin (BCG)

Summary

Background:

Non-muscle-invasive bladder cancer is in the early stages. But it usually comes back after treatment. The drugs Vicineum and Durvalumab may help the immune system find and destroy cancer cells.

Objective:

To test if the drugs Durvalumab and Vicineum together are safe and effective to treat people with bladder cancer that has not spread to the muscle in the bladder.

Eligibility:

People ages 18 and older who have bladder cancer that has not spread to the muscle in the bladder and was treated unsuccessfully with Bacillus Calmette-Guerin

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Tumor sample from previous surgery. If one is not available, they will have a biopsy: A small piece of tumor is removed.

Cystoscopy to examine the inside of the bladder. This may include a biopsy or removing tumors.

Computed tomography (CT) or magnetic resonance imaging (MRI): They lie in a machine that takes pictures of the body.

Electrocardiogram to test heart function

Participants will receive Durvalumab and Vicineum in 2 phases:

First phase: Durvalumab every 4 weeks and Vicineum once a week for 3 months

Second phase: Durvalumab every 4 weeks and Vicineum once every other week

Participants will have tumor samples taken every 3 months. They will have blood and urine tests throughout the study.

Participants will continue treatment for up to 2 years.

Participants will have a visit about 30 days after their last treatment. This includes blood and urine tests. It may include a cytoscopy or additional biopsies.

Conditions

• Urinary Bladder Neoplasms

Interventions

DRUG

Durvalumab

Durvalumab 1500 mg is administered intravenously (IV) once every 4 weeks for 12 months with an option to continue therapy for an additional 12 months (total of 24 months) provided that, participant is tolerating therapy and remains free of recurrent high grade NMIBC (see Treatment Period below). The dose of durvalumab is 1500 mg. If optional maintenance therapy continued in the second year, durvalumab 1500 mg will be administered intravenously once every 3 months to provide an immune boost.

DRUG

Vicineum

Vicineum is administered in a 12-week Induction Phase followed by a Maintenance Phase for at least one year with an option for a total of up to 2 years of treatment. During the Induction Phase, Vicineum is administered once weekly for 12 weeks. During the Maintenance Phase, Vicineum is administered every other week. The dose of Vicineum is 30 mg in 50 mL of saline.

DRUG

Acetaminophen

Acetaminophen or equivalent medications per institutional standard may be administered at the discretion of the investigator.

DRUG

Antihistamine

Antihistamine (e.g., diphenhydramine) or equivalent medications per institutional standard may be administered at the discretion of the investigator.

PROCEDURE

Bladder Biopsy

Bladder biopsy at screening and every 3 months before each cystoscopy per schema.

PROCEDURE

TURBT

Transurethral resection of a bladder tumor (TURBT) at screening and every 3 months before each cystoscopy per schema.

PROCEDURE

Cystoscopy

Urine cytology at screening and every 3 months before each cystoscopy per schema.

DIAGNOSTIC_TEST

Urine cytology

Urine cytology at baseline and every 3 months before each cystoscopy per schema.

DIAGNOSTIC_TEST

Electrocardiogram

Electrocardiogram (ECG) at screening, pre-durvalumb infusion and as clinically indicated during the trial.

DIAGNOSTIC_TEST

CT

Computed tomography (CT) at screening and every 12 months while on study.

DIAGNOSTIC_TEST

MRI

Magnetic resonance imaging (MRI) at screening and every 12 months while on study.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Raju Chelluri, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-06-07

Primary Completion

2022-08-01

Completion

2022-10-17

FDA Drug

Yes

Countries

• United States

Study Locations