Combining CRLX101, a Nanoparticle Camptothecin, With Enzalutamide in People With Progressive Metastatic Castration Resistant Prostate Cancer Following Prior Enzalutamide Treatment

Background: Some prostate cancer keeps growing even when testosterone in the body drops to very low levels. This is called castrate-resistant prostate cancer. One treatment is enzalutamide. This is a modern hormonal therapy. But it only works for a certain amount of time and then the cancer becomes resistant to it. Researchers want to see if adding the treatment CRLX101 (formerly IT-101) could make enzalutamide work again for people who have already had it. Objective: To test a new way of treating prostate cancer using CRLX101 plus enzalutamide in people with certain prostate cancer who already had enzalutamide treatment. Eligibility: Adults ages 18 years and older with metastatic, castration-resistant prostate cancer who have had enzalutamide treatment Design: Participants will be screened with a medical history and physical exam. They will have blood and urine tests. They will have a scan of the chest/abdomen/pelvis. They will have a bone scan. Participants will get treatment in cycles. A cycle lasts 28 days. They will take enzalutamide by mouth once a day. They will get CRLX101 through an intravenous (IV) every 1 or 2 weeks. Participants will repeat screening tests throughout the study. Participants will have a follow-up visit 3-4 weeks after they stop taking the study drug. They will repeat most screening tests and have an electrocardiogram.