A Hoosier Cancer Research Network study for adult patients with muscle-invasive bladder cancer (MIBC) will help doctors determine whether some patients could forego bladder removal and receive standard chemotherapy drugs and the immunotherapy drug, nivolumab. It will also test whether adding nivolumab to chemotherapy drugs, gemcitabine and cisplatin, works better than chemotherapy alone for treating bladder cancer that has invaded the muscle layer of the bladder. Correlative tests, including genomic sequencing, will play a critical role in identifying biomarkers that might help determine which patients could be spared the removal of their bladders.

People with MIBC are typically treated with chemotherapy and a radical cystectomy, or surgical removal of the bladder. Chemotherapy preceding surgery has been shown to increase the likelihood of curing bladder cancer compared to surgery alone.

The phase II study, “Neoadjuvant gemcitabine, cisplatin, plus nivolumab in patients with muscle-invasive bladder cancer with selective bladder sparing,” also known as HCRN GU16-257, is now enrolling eligible subjects, ages 18 and above, at Tisch Cancer Institute at Mount Sinai in New York, NY; City of Hope in Duarte, Calif.; Huntsman Cancer Institute in Salt Lake City, Utah; Oregon Health and Science University in Portland, Ore.; Penn Medicine Abramson Cancer Center in Philadelphia, Pa.; University of Wisconsin Carbone Cancer Center in Madison, Wis.; and USC Norris Comprehensive Cancer Center in Los Angeles, Calif. Up to 76 subjects will participate in the study.

All study participants will receive 4 cycles of gemcitabine and cisplatin, plus nivolumab provided treatment is tolerated. After completing 4 cycles of this treatment, subjects will undergo testing to determine how their cancer has responded. Testing will include an MRI or CT scans of the abdomen and pelvis and a CT of the chest; a cystoscopy, a scope to look in the bladder; and biopsies of the lining of the bladder.

Researchers will analyze the effects of adding nivolumab to the standard chemotherapy regimen gemcitabine and cisplatin, and they hope to learn if nivolumab enhances how chemotherapy treats cancer. Nivolumab is approved by the U.S. Food and Drug Administration to treat a variety of cancers, including previously treated locally advanced or metastatic bladder cancer. However, nivolumab has not been approved for patients with early stage bladder cancer. The use of nivolumab in combination with gemcitabine and cisplatin for this patient population is considered investigational.

Some cancer cells have mutations or defects in genes that are involved in repairing DNA damage. While those cancer cells proliferate, many genes become altered. Several studies have shown that if a patient’s bladder cancer has a mutation in one of these genes, then that cancer is receptive to cisplatin, the chemotherapy drug used in this study. Research has also shown that patients with a high tumor mutation burden are more likely to respond to immunotherapy, especially with drugs that are PD-1 inhibitors, said Matthew Galsky, MD, a medical oncologist at Tisch Cancer Institute at Mount Sinai and sponsor-investigator of the study. He said knowing patients could respond well to cisplatin and immunotherapy may make them ideal candidates for combination therapy.

Dr. Galsky said the goal is for patients with mutated genes to proceed with chemotherapy and immunotherapy, which could eradicate the bladder cancer, without requiring removal of the bladder. “If there is no evidence of cancer and the patient’s genomic sequencing revealed that they had a mutation in a DNA damage response gene in that initial specimen, then they will have the opportunity not to have their bladder removed,” he said.

“To be able to do this type of trial, we require biomarkers that predict not a clinical complete response, but a pathological complete response,” Dr. Galsky continued. “This means when the bladder is out of the patient and the pathologist has it in the pathology lab and they dissect it, they can’t find any cancer. We need biomarkers to determine that, and that’s what these DNA damage response genes are. They’re biomarkers which in prior studies have predicted likelihood of having a pathological complete response.”

For more information about this research study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03558087).

Support for this study is provided by Bristol-Myers Squibb Company (BMS).

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.