Pertuzumab, Trastuzumab, Hyaluronidase-zzxf and Enzalutamide for Treatment of Metastatic Castration-Resistant Prostate Cancer

PRIMARY OBJECTIVE: I. Evaluate the preliminary efficacy of the combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf plus enzalutamide with regard to objective response rate (Prostate Cancer Clinical Trials Working Group 3 \[PCWG 3.0\]) in enzalutamide-refractory metastatic castration-resistant prostate cancer. SECONDARY OBJECTIVES: I. Estimate the radiographic progression-free survival for this combination. II. Estimate the overall survival for this combination. EXPLORATORY OBJECTIVES: I. Assessment of this combination for adverse events according to clinical judgment and patient-reported outcomes (Patient Reported Outcomes-Common Terminology Criteria for Adverse Events \[PRO-CTCAE\] - Prostate Cancer). II. Assessment of patient quality of life using Functional Assessment of Cancer Therapy- Prostate (FACT-P) questionnaire. CORRELATIVE OBJECTIVES: I. Determine the correlation between outcomes as above and systemic NRG-1 levels at baseline and over time. II. Determine the correlation between outcomes as above and change in HER2/HER3/androgen receptor (AR) gene signatures. OUTLINE: Patients receive pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneously (SC) on day 1 of each cycle and enzalutamide orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO), biopsy, computed tomography (CT), and magnetic resonance imaging (MRI) scans and collection of blood samples throughout the study. After completion of study treatment, patients are followed up every 3 months until progressive disease then every 6 months thereafter.