New clinical trial will test COXEN’s ability to choose best therapy for patients with advanced bladder cancer

Histopathology of urothelial carcinoma of the urinary bladder.

The Center for Cancer Research, part of the National Cancer Institute, is now enrolling participants for a clinical trial that will evaluate whether analyzing a tumor’s genetic profile can identify which approved anticancer drugs are most likely to benefit individual patients whose bladder cancer has stopped responding to standard treatments.

Few options are available to treat bladder cancer once it has spread, but many chemotherapy drugs have never been tested in patients with the disease. Researchers hope that by using a computational method called Co-eXpression ExtrapolatioN (COXEN), they will be able to select the optimal treatment for patients with advanced urothelial cancer, the most common form of bladder cancer.

COXEN uses genetic data to compare a patient’s tumor to cells with known drug response profiles. Physicians can use that information to tailor therapy for each patient. This approach to cancer treatment is an example of personalized medicine.

“Right now we’re [treating advanced bladder cancer] using drugs based on data from clinical trials. With this study, we can, in a very controlled setting, test novel therapies that haven’t been tested in this disease,” says Andrea Apolo, a physician-scientist investigator in the Center for Cancer Research’s Genitourinary Malignancies Branch and principal investigator of the study.

The clinical trial will take place at the National Institutes of Health Clinical Center, the world’s largest dedicated research hospital, in Bethesda, Maryland. Patients who qualify for the study are treated free of charge. The study is open to patients with metastatic urothelial cancer that has become resistant to standard therapies for this disease. Each patient’s treatment will be individually selected from among 75 different FDA-approved chemotherapies, using the COXEN algorithm to predict the tumor’s response to each drug.

All 75 drugs have been tested against the NCI-60, a collection of 60 cell lines derived from many types of human tumors. Study participants will have their tumors biopsied so that researchers can determine the tumor’s genetic profile. Then, using this data, the COXEN algorithm will compare each patient’s tumor to the NCI-60 cell lines and predict which chemotherapies are likely to be effective for the patient. For each of the 75 drugs, the program will predict the tumor’s likely responsiveness. “This is a unique way of assessing the sensitivity of a tumor to the antineoplastic drugs we have available now,” Apolo says.

Patients may receive a single drug or multiple drugs in combination. If their disease worsens during the study, patients can choose to have another biopsy and a second treatment based on COXEN’s predictions.

Ultimately, Apolo hopes that COXEN will enable a future where community oncologists can efficiently select the best therapies for their patients with advanced bladder cancer. Right now, she notes, the complete process involves many steps and a team of experts. The current study, which will include 20 patients and is expected to run for up to two years, aims to determine whether clinicians can use COXEN to choose the best next therapy for a patient’s urothelial cancer within three weeks. If it is successful, Apolo and her colleagues plan to launch a larger, randomized clinical trial to compare the effects of COXEN-selected treatments to treatments chosen by a physician without the aid of the algorithm.

Information about this Center for Cancer Research clinical trial may be found here.  Information about clinical trials supported by the National Cancer Institute may be found at

Summary Posted: Thu, 09/01/2016