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

Inclusion Criteria

• •Patients must have histologically or cytologically confirmed prostate cancer confirmed by either the Laboratory of Pathology at the national Institutes of Health (NIH) Clinical Center or Walter Reed National Military Medical Center at Bethesda prior to starting this study. If no pathological specimen is available, patients may enroll with a pathologist's report showing a histological diagnosis of prostate cancer and clinical course consistent with the disease.
• •Patients must have progressive metastatic castration-resistant prostate cancer mCRPC. There must be radiographic evidence of disease progression or biochemically (rising prostate-specific antigen (PSA) levels on successive measurements) recurring disease despite adequate testosterone suppression.
• •Progression must be evidenced and documented by any of the following parameters:
• •* PSA progression defined by a minimum of two rising PSA levels with an interval of greater than or equal to 1 week between each determination
• •* Appearance of one or more new lesions consistent with prostate cancer on bone scan
• •* New or growing lesions on computed tomography (CT) scan
• •Patients must have metastatic disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(64).
• •Patients must have received treatment with prior enzalutamide for two or more cycles and must have had evidence of disease progression while on enzalutamide.
• •Patients who have received antiandrogens such as flutamide, bicalutamide, or nilutamide for \>6 months immediately before enrollment on this study must be off treatment for 4 weeks (6 weeks for bicalutamide) and demonstrate a continued rise in PSA. Patients on antiandrogens for \<6 months must be off medication for 2 weeks.
• •Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of enzalutamide and CRLX101 in patients \<18 years of age and prostate cancer is not common in children \<18 years of age, children are excluded from this study.
• •Patients must have adequate organ and marrow function as defined below:
• •* leukocytes greater than or equal to 3,000/mcL
• •* absolute neutrophil count greater than or equal to 1,500/mcL
• •* platelets greater than or equal to 100,000/mcL
• •* total bilirubin within normal institutional limits; for patients with Gilberts syndrome, total bilirubin less than or equal to 3.0 mg/dL
• •* hemoglobin greater than or equal to 9g/dL
• •* serum albumin greater than or equal to 2.8 g/dL
• •* Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)Serum glutamic-pyruvic transaminase (SGPT) less than or equal to 2.5 times institutional upper limit of normal (\<5 times institutional ULN for liver metastases)
• •* creatinine within 1.5 times normal institutional limits
• •OR
• •-creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
• •Patients must have castrate levels of testosterone (\<50 ng/dL \[1.74 nmol/L\]).
• •Patients must have undergone bilateral surgical castration or must continue on gonadotropin-releasing hormone (GnRH) agonists/antagonists for the duration of the study.
• •Patients on 5-alpha reductase inhibitors such as finasteride or dutasteride must stop medication at least 28 days prior to study entry.
• •The effects of enzalutamide and CRLX101 (formerly IT-101) on the developing human fetus are unknown. For this reason and because androgen receptor antagonists and topoisomerase I inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, all study subjects must agree to use a condom during the study treatment period and for 120 days following the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
• •Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
• •Ability of subject to understand and the willingness to sign a written informed consent document.
• •interactions.
• •INCLUSION OF MINORITIES AND WOMEN:
• •Men of all races and ethnic groups are eligible for this trial. Women are excluded as prostate cancer does not exist in this population.