A new Hoosier Cancer Research Network study may help researchers determine whether the choice of chemotherapy regimens used in combination with the immunotherapy drug nivolumab could make a difference in outcomes for patients with metastatic bladder cancer.

Standard treatment for metastatic bladder cancer, also known as urothelial carcinoma, usually involves cisplatin-based chemotherapy. However, a large proportion of patients are not eligible for this treatment due to impaired renal function and other physical or age-related limitations. Standard options for these cisplatin-ineligible patients often include carboplatin-based therapies.

Recent studies have shown that single-agent immunotherapy drugs that target the programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) pathway as first-line treatment can benefit these patients. However, only about 20 to 25 percent of patients respond to single-agent PD-1/PD-L1 inhibitors. Researchers are now testing whether adding chemotherapy regimens to PD-1/PD-L1 therapy might lead to improved response rates.

In this new phase II study, known as HCRN GU16-287, researchers will test two chemotherapy regimens in combination with the anti-PD-1 agent nivolumab.

The question of whether one chemotherapy regimen is more advantageous than another in combination with nivolumab has not been adequately explored, according to the study’s sponsor-investigator, Matthew D. Galsky, MD, of the Icahn School of Medicine at Mount Sinai/Tisch Cancer Institute (pictured above). “Combination regimens have generally advanced to the clinic without consideration of the potential importance of the choice of cytotoxic agent,” Dr. Galsky said.

Study participants will be randomly assigned to one of two treatment groups. The first group will receive up to six cycles of nivolumab in combination with gemcitabine and carboplatin, while the second group will receive up to six cycles of nivolumab in combination with gemcitabine and oxaliplatin. Both groups will then receive up to 12 cycles of maintenance nivolumab.

The main goal of the study is to estimate the proportion of patients in each treatment group whose tumors respond to treatment.

Each drug in this study has been approved by the U.S. Food and Drug Administration to treat certain types of cancer. However, the use of nivolumab in combination with gemcitabine and carboplatin, and the use of nivolumab in combination with gemcitabine and oxaliplatin are investigational. Investigational means that these combinations have not been approved by the FDA to treat this type of cancer.

The study is now open to accrual at the Icahn School of Medicine at Mount Sinai/Tisch Cancer Institute. Additional sites are expected to open soon.

Bladder cancer is the sixth most commonly diagnosed cancer in the United States, with more than 79,000 new cases and 16,800 deaths estimated in 2017. The current standard approach for patients with metastatic disease is chemotherapy, and only recently has there been an FDA-approved therapy for patients with metastatic disease who progress on first-line therapy.

Funding for HCRN GU16-287 is provided by Bristol-Myers Squibb Company.

The study will enroll up to 48 subjects with metastatic urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Additional eligibility requirements must be met to enroll.

For more information about this study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03451331).

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 180 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 7,500 subjects have participated in Hoosier Cancer Research Network clinical trials.