Bortezomib in Patients With Metastatic Castration-Resistant Prostate Cancer With PTEN Deletion

NCT06029998 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCI168505
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the anti-tumor activity of bortezomib in participants with Metastatic Castration Resistant Prostate Cancer (mCRPC) with PTEN Deletion. The main question\[s\] it aims to answer is if the use of bortezomib will result in a decline in PSA for participants. Participants will receive a sub-cutaneous injection of bortezomib for up 8 cycles. Each cycle is about 21 days.

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• The proportion of patients achieving PSA decline of ≥ 30% from baseline will be considered a response.

  To evaluate the antitumor activity of bortezomib in patients with metastatic castration-resistant prostate cancer (mCRPC) with PTEN deletion as assessed by prostate-specific antigen (PSA) 30% response rate.

  Up to 6-8 cycles of treatment. Each cycle is 21 days.

Secondary Outcomes (13)

• The proportion of patients achieving PSA decline of ≥ 50% (PSA50) compared to the baseline value prior to starting study treatment.

  Up to 6-8 cycles of treatment. Each cycle is 21 days.

• Duration of PSA response as defined as the interval of time from PSA decline of ≥ 50% to PSA progression as defined by PCWG3 criteria.

  Until progression or end of study. Study anticipated to be about 4 years.

• PSA PFS as defined as the interval of time from study drug initiation to the time of PSA progression as defined by PCWG3 criteria.

  Until progression or end of study. Study anticipated to be about 4 years.

• ORR as defined as the proportion of patients with measurable disease achieving a confirmed partial response (PR) and complete response (CR) as assessed by PCWG3-modified RECIST

  Until progression or end of study. Study anticipated to be about 4 years.

• DoR as defined as the interval of time from the date of initial documented response (PR or better per PCWG3-modified RECIST 1.1) to the time of progression, the start of a new therapy, or death from any cause.

  Until progression or end of study. Study anticipated to be about 4 years.

Study Arms (1)

Bortezomib

EXPERIMENTAL

bortezomib starting at a dose of 1.3 mg per square meter of the body-surface area (BSA) subcutaneously on days 1, 4, 8, and 11 in a 21-day cycle.

Drug: Bortezomib

Interventions

Bortezomib DRUG

sub-cutaneous injection of bortezomib for 6-8 cycles of treatment.

Bortezomib

Eligibility Criteria

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

You may qualify if:

• Male subject aged ≥ 18 years
• Histologically or cytologically confirmed prostatic adenocarcinoma without small cell histology
• Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L)
• Prior treatment with at least one prior Androgen Receptor Pathway Inhibitor (ARPI), defined as second-generation anti-androgen therapies that include, but are not limited to, abiraterone acetate, enzalutamide, apalutamide, and darolutamide.
• No prior systemic chemotherapy treatment for mCRPC disease (e.g., docetaxel, or cabazitaxel).
• Available tumor tissue (archival tissue, or, if no archival tissue is available, must be able to undergo biopsy for fresh tumor tissue). If tumor tissue is unavailable, results of ATAD1 immunohistochemistry must be available.
• PTEN deletion on next generation sequencing
• Must have progressive mCRPC per the treating investigator
• ECOG Performance Status ≤ 2.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 10 g/dL
• Hepatic:

You may not qualify if:

• Neuropathy grade ≥ 2
• Receiving other investigational agents.
• Prior systemic anti-cancer therapy or any investigational therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter. Patients can continue ADT and bone strengthening agents while on treatment.
• Prior radiotherapy within 14 days prior to the first dose of study treatment.
• Note: Palliative radiation therapy may be completed up to 14 days prior to starting study therapy provided that no clinically significant treatment related toxicities are present at the time of study therapy initiation per treating investigator.
• Major surgery within 14 days prior to starting study drug or who have not fully recovered from major surgery per treating investigator.
• The diagnosis of another malignancy within ≤ 2 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration per treating investigator (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix).
• Known brain metastases or cranial epidural disease.
• Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Participants must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (e.g., deep venous thrombosis (DVT), pulmonary embolism (PE)) within 3 months before the first dose. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 3 months are allowed if stable, asymptomatic, and treated with a stable dose of anticoagulation for at least 1 week before first dose of study treatment.
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment. If a single ECG shows a QTcF with an absolute value \> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• Known congenital long QT.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

Bortezomib

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Umang Swami, MD, MS

  University of Utah

  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

Model Details: A modified intent-to-treat data set will be used for both safety and efficacy endpoint analysis. All participants who have received one dose of study medication will be included in all efficacy and safety data sets. Participants who fail to begin study therapy will be replaced.

Study Record Dates

• First Submitted: September 1, 2023
• First Posted: September 8, 2023
• Study Start: March 11, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 7, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)