Patients with a noninvasive, low-grade form of bladder cancer often need multiple surgeries to treat recurrences, which are common. A new chemoablative gel currently under study at Penn State Health may eliminate the need for those procedures.
Penn State Health is one of 25 centers in the United States participating in a phase 2, single-arm clinical trial of UGN-102 — a gel form of the chemotherapy drug mitomycin C, which is widely used to prevent tumors from recurring — as a primary treatment for individuals with low-grade non-muscle-invasive bladder cancer (NMIBC) with intermediate risk of recurrence. UGN-102 enters the bladder as a liquid via catheter, but once inside, it gelatinizes and coats the bladder wall to ablate tumors. After six hours, the drug liquefies and patients void it through the urine.
“Instead of only preventing tumors from returning, UGN-102 allows us to treat them,” says Penn State Health Professor and Chief of Urology Jay Raman, MD, FACS, who is managing the study at Penn State Health. “It releases a higher tissue concentration of mitomycin C, which ablates the primary tumor and also treats unseen areas in the bladder that may harbor microscopic disease. Mitomycin C has been on the market for years, and we use it in standard practice to prevent bladder tumors from recurring following surgery. UGN-102 builds on current standards of care. We’re using an existing drug but delivering it in a new, noninvasive way.”
The Risks and Burdens of Standard Care
A nonsurgical treatment would be welcome news for patients with NMIBC, which is a common form of bladder cancer — the sixth most common cancer in the United States, with more than 80,000 new cases expected in 2019, according to the National Cancer Institute. Bladder cancer is, primarily, a disease of older populations. People ages 55 or older comprise 92% of cases, and the average age at diagnosis is 73. Many individuals with NMIBC with intermediate likelihood of recurrence have comorbidities that can make standard care — typically, cystoscopy with an electrocautery device to resect the tumor, often followed by intravesical therapy — risky.
“Often, patients are taking anticoagulants, so there’s a risk of bleeding,” Dr. Raman says. “Many patients need a catheter to remain in the bladder after surgery, which increases the risk of infection. Additionally, multiple procedures lead scar tissue to form in the bladder that may reduce its ability to contract and can cause chronic pain.”
A Potentially Game-Changing Option
The nationwide study of UGN-102’s efficacy and safety began in October 2018 and is scheduled to conclude in September 2020. Researchers plan to recruit approximately 60 patients. Penn State Health has enrolled three participants and would like to register three to four more.
Participants receive UGN-102 weekly for six weeks. When stored at cool temperatures, UGN-102 is liquid, but exposure to body temperatures turns it gelatinous. That transition is a key differentiator compared with liquid drugs used to treat bladder tumors.
“Liquid chemotherapeutic agents that are standard of care may not contact all portions of the bladder because they may settle at the bottom,” Dr. Raman says. “The drug may not reach the nondependent portion of the bladder. With UGN-102, the gel covers the entire bladder wall and sticks to it.”
Cystoscopies at three, six, nine and 12 months after treatment allow urologists to assess participants’ responses. Individuals who have not responded to treatment can transition to standard surgical care. Researchers and patients have reason to be optimistic about UGN-102’s potential: The product’s developer announced earlier this year that in a phase 3 clinical trial of a mitomycin gel formulation to treat low-grade upper-tract urothelial cancer, 57% of patients were cancer-free four to six weeks after treatment. All of the participants who were cancer-free and continued to be evaluated showed no signs of the disease six months after treatment.
For Dr. Raman, the UGN-102 trial is evidence of Penn State Health’s willingness to embrace innovation in pursuit of effective, less invasive treatments for patients.
“Undertaking trials like this one shows we’re willing to think beyond the standard of care we currently offer and explore how to improve treatment for NMIBC,” Dr. Raman says. “Being one of 25 participating centers in the country highlights our excellence in bladder cancer among our peers.”
For information about the Division of Urology at Penn State Health Milton S. Hershey Medical Center, visit hmc.pennstatehealth.org/urology.