Neratinib in Patients With Metastatic Castration-Resistant Prostate Cancer

NCT04781374 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 20-659
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is examining whether Neratinib has any activity in participants with prostate cancer that has spread and is no longer responding to hormonal treatment. \- The names of the study drug involved in this study is neratinib.

Conditions

Metastatic Prostate Adenocarcinoma; Castration-resistant Prostate Cancer; Prostate Cancer; Prostate Cancer Metastatic

Keywords

Metastatic Prostate Adenocarcinoma; Castration-resistant Prostate Cancer; Prostate Cancer; Prostate Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Response Rate to Neratinib

  defined by PSA response and/or radiographic response after three 28-day cycles of treatment.

  84 days

Secondary Outcomes (6)

• Best PSA response

  24 Months

• Best Radiographic Response

  Baseline, Every 3 Cycles through study completion, up to 24 months.

• Duration of Response

  Baseline, Every 3 Cycles through study completion, up to 24 months.

• Progression Free Survival

  24 Months

• Overall Survival

  6 Months

Study Arms (1)

Neratinib

EXPERIMENTAL

The research study procedures include: screening for eligibility and study treatment including evaluations and follow up visits. \- Neratinib-once daily with 28 consecutive days defined as a treatment cycle

Drug: Neratinib

Interventions

Neratinib DRUG

Oral, once daily with 28 consecutive days defined as a treatment cycle, dosage per protocol ,

Also known as: Nerlynx

Neratinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed metastatic prostate adenocarcinoma (secondary components of variant histology are acceptable).
• Castration-resistance, with progression on medical/surgical castration and confirmed baseline testosterone \<50ng/dL
• Ongoing castration, either with prior orchiectomy or ongoing gonadotropin releasing hormone (GnRH) agonist/antagonist therapy as per investigator discretion
• Anti-resorptive therapy (e.g. denosumab, bisphosphonates) is allowable at any point
• Prior progression on (or intolerance of) at least one androgen-receptor signaling inhibitor(i.e. abiraterone, enzalutamide, apalutamide, darolutamide). Progression is per investigator and can include prostate specific antigen (PSA), symptomatic, and/or radiographic progression. There is no limit to prior therapies, nor any requirement on taxane treatments.
• Positive biomarker (phospho human epidermal growth factor receptor 2, pHER2) assessment on baseline tissue. Archival tissue is acceptable but must have been acquired during or after prior abiraterone and/or enzalutamide therapy and must meet tissue specifications outlined in the biomarker assessment section of the protocol. If suitable archival tissue is not available, then the patient must be willing to undergo a research biopsy to obtain tissue for biomarker assessment.
• Evaluable for response, defined as at least one of the following:
• Baseline PSA \>=2.0 ng/mL
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Ability to understand and willingness to sign informed consent.
• Willingness to undergo research biopsy on study, as well as at baseline if needed to obtain tissue for biomarker assessment.
• Age \>=18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Adequate organ and marrow function as defined below:
• leukocytes ≥2,000/mcL

You may not qualify if:

• Use of a strong CYP3A4/CYP2C8 inducer/inhibitor within 3 half-lives prior to first dose of study treatment
• Participants who are receiving any other investigational agents
• History of allergic reaction to HER2 inhibitors
• Child-Pugh class C hepatic impairment
• Current use of a proton pump inhibitor (no specific wash-out period)
• Corrected QTc interval \>450 msec with institutional standard correction formula. One EKG is sufficient. In the case of potentially reversible causes of QT prolongation (e.g. medications, electrolyte abnormalities), EKG may be repeated once during screening and that result may be used to determine eligibility.
• 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.
• Uncontrolled baseline diarrhea or uncontrolled predisposition to intermittent diarrhea, e.g. uncontrolled inflammatory bowel diseases.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Puma Biotechnology, Inc.: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Center

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

neratinib

Condition Hierarchy (Ancestors)

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

Study Officials

• David Einstein, MD

  Beth Israel Deaconess Medical Center

  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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 26, 2021
• First Posted: March 4, 2021
• Study Start: May 21, 2021
• Primary Completion: September 24, 2021
• Study Completion: September 24, 2021
• Last Updated: July 11, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Locations

US (3)