Trial Title:
Pertuzumab, Trastuzumab, Hyaluronidase-zzxf and Enzalutamide for Treatment of Metastatic Castration-Resistant Prostate Cancer
NCT ID:
NCT05730712
Condition:
Castration-Resistant Prostate Carcinoma
Stage IVB Prostate Cancer AJCC v8
Conditions: Official terms:
Prostatic Neoplasms
Trastuzumab
Pertuzumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (HP, enzalutamide)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood and tissue samples
Arm group label:
Treatment (HP, enzalutamide)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (HP, enzalutamide)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (HP, enzalutamide)
Other name:
EC
Intervention type:
Drug
Intervention name:
Enzalutamide
Description:
Given PO
Arm group label:
Treatment (HP, enzalutamide)
Other name:
ASP9785
Other name:
MDV3100
Other name:
Xtandi
Intervention type:
Drug
Intervention name:
Hyaluronidase-zzxf/Pertuzumab/Trastuzumab
Description:
Given SC
Arm group label:
Treatment (HP, enzalutamide)
Other name:
Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf
Other name:
Pertuzumab/Trastuzumab/Hyaluronidase-zzxf
Other name:
Phesgo
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (HP, enzalutamide)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Treatment (HP, enzalutamide)
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.
Detailed description:
PRIMARY OBJECTIVE:
I. Evaluate the combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf plus
enzalutamide in enzalutamide-refractory metastatic castration-resistant prostate cancer
(mCRPC) in improving objective response rate among patients with measurable disease
(Prostate Cancer Clinical Trials Working Group 3 [PCWG 3.0]).
SECONDARY OBJECTIVES:
I. Evaluate this combination for radiographic progression-free survival at 6 months.
II. Evaluate this combination for overall survival at 12 months.
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) and
enzalutamide orally (PO) on study. Patients undergo echocardiography (ECHO), biopsy,
computed tomography (CT), and magnetic resonance imaging (MRI) scans. Patients also
undergo collection of blood and tissue samples.
Criteria for eligibility:
Criteria:
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 =< 1.5 x upper limit of normal (ULN)
- REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x
ULN (=< 5 x ULN for patients with liver involvement).
- REGISTRATION: PT/INR/aPTT =<1.5 x ULN OR if patient is receiving anticoagulant
therapy and INR or aPTT is within target range of therapy.
- REGISTRATION: Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault
formula.
- REGISTRATION: Left ventricular ejection fraction (LVEF) >= 50% =< 15 days prior to
registration.
- REGISTRATION: Provide written informed consent.
- REGISTRATION: Ability to complete questionnaire(s) by themselves or with assistance.
- REGISTRATION: Willingness to provide mandatory blood specimens for correlative
research.
- REGISTRATION: Willingness to provide mandatory tissue specimens for correlative
research.
- REGISTRATION: Willing to return to enrolling institution for follow-up (during the
Active Monitoring Phase of the study).
Exclusion Criteria:
- 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)
- 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
immunocompromised state, are eligible for this trial.
- REGISTRATION: Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Or psychiatric illness/social situations that would limit compliance with study
requirements.
- REGISTRATION: Currently receiving any other investigational agent which would be
considered as a treatment for the primary neoplasm.
- REGISTRATION: Other active malignancy =< 3 years prior to registration. EXCEPTIONS:
Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a
history of prior malignancy, they must not be receiving other specific treatment
(e.g., other hormonal therapy, chemotherapy) for their cancer.
- REGISTRATION: History of myocardial infarction =< 6 months, or congestive heart
failure requiring use of ongoing maintenance therapy for life-threatening
ventricular arrhythmias.
- REGISTRATION: Known hypersensitivity to pertuzumab, or trastuzumab, or
hyaluronidase, or to any of its excipients.
- REGISTRATION: Requirement for drugs or substances which can interfere with the
actions of the study drugs (enzalutamide or
pertuzumab/trastuzumab/hyaluronidase-zzxf). Consult pharmacist for review.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Alan H. Bryce, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Winston W. Tan, M.D.
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Jacob Orme, M.D., Ph.D.
Email:
Principal Investigator
Start date:
March 8, 2024
Completion date:
October 2025
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05730712
https://www.mayo.edu/research/clinical-trials
