Phase II Trial of Enzalutamide and PDS01ADC in PET Positive Recurrent Prostate Cancer (pprPC) Without Testosterone Lowering Therapy
Background: Prostate cancer may return after treatment in 30,000 to 50,000 people each year. There is no clear best way to treat these people. Better treatments are needed.
Objective: To test a study drug (enzalutamide), both alone and combined with a second drug (PDS01ADC), in people with prostate cancer that returned after treatment.
Eligibility: People aged 18 years and older with prostate cancer that returned after treatment.
Design: Participants will be screened. They will have a physical exam, with blood tests. All their urine will be collected for 24 hours. They will have imaging scans of their chest, abdomen, pelvis, and bones. Their ability to perform everyday activities will be assessed. They may opt to give a stool sample. Participants will be treated in 4-week cycles. Enzalutamide is a pill taken by mouth once a day, every day. All participants will be given a supply of this drug to take at home. PDS01ADC is injected under the skin once a month, on the first day of each cycle. Half of the participants will receive both drugs. All participants will visit the clinic once a month. Each visit should last no more than 8 hours. Blood and urine tests will be repeated. All participants will receive the study treatment for 3 cycles. Some participants may need 3 more cycles of treatment with enzalutamide only. This re-treatment can be done only once. Participants will have a follow-up visit 1 month after they finish treatment. After that, they will have visits every 6 weeks for up to 5 years. Imaging scans and blood tests will be repeated. ...
⁃ Participant must provide documentation of histologic or cytological confirmation of prostate cancer or tumor sample for diagnosis confirmation. Note: in the absence of pathology or documentation, participant must have a rising PSA, PSMA+ disease, and his history consistent with prostate cancer as documented by the investigator.
⁃ History of primary treatment for prostate cancer (either surgery or radiation).
⁃ Prostate-specific antigen (PSA) doubling time within less than 12 months.
⁃ Testosterone \>100 ng/dL.
⁃ Age \>=18 years.
⁃ Evidence of prostate cancer on PSMA PET/CT scan.
⁃ Eastern Cooperative Oncology Group (ECOG) performance status \<2.
⁃ Men must agree to use an effective method of contraception (barrier or surgical sterilization) after study entry and for 3 months after completion of enzalutamide or PDS01ADC therapy whatever comes later.
⁃ Participants must have adequate organ and marrow function as defined below:
∙ Absolute neutrophil count (ANC) \>=1,500/microliter, without granulocyte colony-stimulating factor (G-CSF) support
‣ Platelets \>=100,000/microliter
‣ Aspartate aminotransferase (AST) /Alanine aminotransferase (ALT) \<=2.5 x institutional upper limit of normal (ULN)
‣ Hemoglobin (Hgb) \>= 10 g/dL (packed red blood cell (pRBC) transfusions are not allowed to achieve acceptable Hgb)
‣ Total bilirubin \<= 1.5 x ULN, OR \<= 3.0 ULN in participants with Gilbert s syndrome
‣ Serum albumin \>= 2.8 g/dL
‣ Creatinine \< 1.5 X institution ULN
• OR
• -Measured or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl) \> 45 mL/min/1.73 m\^2 for participant with creatinine levels \> 1.5 x institutional ULN
⁃ Hepatitis B virus (HBV)-infected participants can be enrolled if HBV DNA is undetectable at screening. Hepatitis C virus (HCV)-infected participants can be enrolled if the HCV RNA level is undetectable at screening. Human immunodeficiency virus (HIV)-positive participants can be enrolled if HIV DNA is undetectable.
⁃ Participants must be able to swallow tablets/capsules.
⁃ Participants must be able to understand and willing to sign a written informed consent document.