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

NCT05730712 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: MC210504NCI-2022-1077321-013057
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests how well pertuzumab, trastuzumab, hyaluronidase-zzxf and enzalutamide works in treating patients with castration-resistant prostate cancer that has spread from where it first started to other places in the body (metastatic). Pertuzumab and trastuzumab are monoclonal antibodies and forms of targeted therapy that attach to a receptor protein called human epidermal growth factor receptor-2 (HER2). HER2 is found on some cancer cells. When pertuzumab or trastuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Hyaluronidase is an endoglycosidase. It helps to keep pertuzumab and trastuzumab in the body longer, so that these medications will have a greater effect. Hyaluronidase also allows pertuzumab and trastuzumab to be given by injection under the skin and shortens their administration time compared to pertuzumab or trastuzumab alone. Chemotherapy drugs, such as enzalutamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pertuzumab, trastuzumab, hyaluronidase-zzxf and enzalutamide may kill more cancer cells.

Conditions

Castration-Resistant Prostate Carcinoma; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  ORR is defined as the proportion of patients who experience either a partial response or complete response as defined by Prostate Cancer Working Group 3 (PCWG3).

  Up to 2 years

Secondary Outcomes (4)

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Incidence of adverse events

  Up to 1 year

• Quality of life (QoL)

  Up to 1 year

Study Arms (1)

Treatment (HP, enzalutamide)

EXPERIMENTAL

Patients receive pertuzumab, trastuzumab, and hyaluronidase-zzxf SC on day 1 of each cycle and enzalutamide PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, biopsy, CT, and MRI scans and collection of blood samples throughout the study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Drug: Enzalutamide; Drug: Hyaluronidase-zzxf/Pertuzumab/Trastuzumab; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (HP, enzalutamide)

Biospecimen Collection PROCEDURE

Undergo collection of blood and tissue samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (HP, enzalutamide)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (HP, enzalutamide)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (HP, enzalutamide)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (HP, enzalutamide)

Questionnaire Administration OTHER

Ancillary studies

Treatment (HP, enzalutamide)

Hyaluronidase-zzxf/Pertuzumab/Trastuzumab DRUG

Given SC

Also known as: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, Pertuzumab/Trastuzumab/Hyaluronidase-zzxf, Phesgo

Treatment (HP, enzalutamide)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (HP, enzalutamide)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• PRE-REGISTRATION: History of myocardial infarction =\< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias.
• PRE-REGISTRATION: Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment.
• EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment.
• PRE-REGISTRATION: Uncontrolled intercurrent non-cardiac illness including, but not limited to:
• Ongoing or active infection
• Psychiatric illness/social situations
• Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
• Any other conditions that would limit compliance with study requirements
• PRE-REGISTRATION: Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.
• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the prostate cancer.
• PRE-REGISTRATION: Thromboembolic event =\< 60 days prior to pre-registration.
• PRE-REGISTRATION: Serious cardiac illness or medical conditions including, but not confined to, the following:
• History of NCI CTCAE v5.0 Grade \>= 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)

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Biopsy; Specimen Handling; enzalutamide; Trastuzumab; pertuzumab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jacob Orme, M.D., Ph.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: February 16, 2023
• Study Start: March 8, 2024
• Primary Completion: April 10, 2025
• Study Completion: April 10, 2025
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

US (3)