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

Inclusion Criteria

• PRE-REGISTRATION: Age >= 18 years.
• PRE-REGISTRATION: Clinically or histologically confirmed diagnosis of second-generation antiandrogen-refractory metastatic castration-resistant prostate cancer.
• PRE-REGISTRATION: Measurable disease as defined by the Prostate Cancer Working Group (PCWG3) criteria.
• PRE-REGISTRATION: Prior treatment required:
• Second generation anti-androgen (2GAA) therapy (e.g., enzalutamide, abiraterone) at any time prior registration.
• PRE-REGISTRATION: Provide written informed consent.
• PRE-REGISTRATION: Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• PRE-REGISTRATION: Ability to complete questionnaire(s) by themselves or with assistance.
• PRE-REGISTRATION: Willingness to provide mandatory blood specimens for correlative research.
• PRE-REGISTRATION: Willingness to provide mandatory tissue specimens for correlative research.
• REGISTRATION: Plasma NRG-1 level >= 4 ng/ml
• REGISTRATION: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
• REGISTRATION: Hemoglobin >= 9.0 g/dL
• REGISTRATION: Absolute neutrophil count (ANC) >= 1500/mm^3
• REGISTRATION: Platelet count >= 100,000/mm^3
• REGISTRATION: Total bilirubin = = 45 ml/min using the Cockcroft-Gault formula.
• REGISTRATION: Left ventricular ejection fraction (LVEF) >= 50% = = 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class >= II
• High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate >= 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second-degree AVblock Type 2 [Mobitz II] or third-degree AV-block)
• Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication
• Angina pectoris requiring anti-angina medication
• Clinically significant valvular heart disease
• Evidence of transmural infarction on electrocardiogram (ECG)
• Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100mmHg)
• PRE-REGISTRATION: Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication.
• PRE-REGISTRATION: Angina pectoris requiring anti-angina medication.
• PRE-REGISTRATION: Clinically significant valvular heart disease.
• PRE-REGISTRATION: Evidence of transmural infarction on electrocardiogram (ECG).
• PRE-REGISTRATION: Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100mmHg).
• PRE-REGISTRATION: History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction [LVSD], left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
• REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception
• REGISTRATION: Failure to recover from any of the following therapies prior to registration:
• Major surgery
• Chemotherapy
• Infection requiring systemic treatment
• REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• REGISTRATION: Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.

NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocomp