Vorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer

NCT ID: NCT06145633

Last Updated: 2026-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-18

Study Completion Date

2027-12-30

Brief Summary

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This phase II trial tests how well vorinostat works in treating patients with prostate-specific membrane antigen (PSMA)-low castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) (mCRPC). Prostate cancer that has not spread to other parts of the body (localized) is typically treated through surgery or radiotherapy, which for many men is curable. Despite definitive local therapy, cancer that has come back after a period of improvement (recurrent) disease develops in 27-53% of men. Often this is detected by measurement of prostate-specific antigen (PSA) without visible evidence of metastatic disease. Lutetium Lu 177 vipivotide tetraxetan (177Lu-prostate specific membrane antigen \[PSMA\]-617) is a new small molecule PSMA-targeted radioactive therapy that has been approved by the Food and Drug Administration for the treatment of adult patients with PSMA-positive mCRPC who have been treated with androgen receptor inhibitors and taxane-based chemotherapy. Vorinostat is used to treat various types of cancer that does not get better, gets worse, or comes back during or after treatment with other drugs. Vorinostat is a drug which inhibits the enzyme histone deacetylase and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat and 177Lu-PSMA-617 may kill more tumor cells in in patients with PSMA-low mCRPC.

Detailed Description

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OUTLINE:

Patients receive vorinostat orally (PO) once a day (QD) for 28 days and then receive gallium Ga 68 gozetotide intravenously (IV) and undergo a positron emission tomography (PET) scan on trial. Patients may go on to receive 177Lu-PSMA-617 IV per standard of care (SOC) on day 1 of each cycle. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) and bone scan on trial and during follow-up, as well as a fludeoxyglucose F-18 (FDG) PET/CT during screening and on trial and single photon emission computed tomography (SPECT)/CT on trial. Patients undergo blood sample collection on trial and may also optionally undergo biopsy during screening and on trial.

After completion of study treatment, patients are followed up every 8 weeks for 6 months and then every 12 weeks for up to 2 years.

Conditions

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Castration-Resistant Prostate Carcinoma Metastatic Prostate Adenocarcinoma Stage IVB Prostate Cancer AJCC v8

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (vorinostat, 177Lu-PSMA-617)

Patients receive vorinostat PO QD for 28 days and then receive gallium Ga 68 gozetotide IV and undergo a PET scan on trial. Patients may go on to receive 177Lu-PSMA-617 IV per SOC on day 1 of each cycle. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT and bone scan on trial and during follow-up, as well as a FDG PET/CT during screening and on trial and SPECT/CT on trial. Patients undergo blood sample collection on trial and may also optionally undergo biopsy during screening and on trial.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Computed Tomography

Intervention Type PROCEDURE

Undergo CT, PET/CT, SPECT/CT

Fludeoxyglucose F-18

Intervention Type OTHER

Undergo FDG PET/CT

Gallium Ga 68 Gozetotide

Intervention Type OTHER

Given IV

Lutetium Lu 177 Vipivotide Tetraxetan

Intervention Type DRUG

Given 177Lu-PSMA-617

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo 68Ga-PSMA-11 PET

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT/CT

Vorinostat

Intervention Type DRUG

Given IV

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type PROCEDURE

Computed Tomography

Undergo CT, PET/CT, SPECT/CT

Intervention Type PROCEDURE

Fludeoxyglucose F-18

Undergo FDG PET/CT

Intervention Type OTHER

Gallium Ga 68 Gozetotide

Given IV

Intervention Type OTHER

Lutetium Lu 177 Vipivotide Tetraxetan

Given 177Lu-PSMA-617

Intervention Type DRUG

Positron Emission Tomography

Undergo 68Ga-PSMA-11 PET

Intervention Type PROCEDURE

Single Photon Emission Computed Tomography

Undergo SPECT/CT

Intervention Type PROCEDURE

Vorinostat

Given IV

Intervention Type DRUG

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection Bone Scintigraphy CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography 18FDG FDG Fludeoxyglucose (18F) fludeoxyglucose F 18 Fludeoxyglucose F18 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose Fluorodeoxyglucose F18 (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC (68Ga)Glu-urea-Lys(Ahx)-HBED-CC 68Ga-DKFZ-PSMA-11 68Ga-HBED-CC-PSMA 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC 68Ga-PSMA 68Ga-PSMA-11 68Ga-PSMA-HBED-CC [68Ga] Prostate-specific Membrane Antigen 11 [68Ga]GaPSMA-11 AAA 517 AAA-517 AAA517 Ga PSMA Ga-68 labeled DKFZ-PSMA-11 Ga-68 labeled PSMA-11 GA-68 PSMA-11 Gallium Ga 68 PSMA-11 Gallium Ga 68-labeled PSMA-11 GALLIUM GA-68 GOZETOTIDE Gallium-68 PSMA Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC GaPSMA PSMA-HBED-CC GA-68 177Lu-labeled PSMA-617 177Lu-PSMA-617 AAA 617 AAA-617 AAA617 Lu177-PSMA-617 Lutetium Lu 177-PSMA-617 LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN Lutetium-177-PSMA-617 Pluvicto Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Medical Imaging, Single Photon Emission Computed Tomography Single Photon Emission Tomography Single-Photon Emission Computed single-photon emission computed tomography SPECT SPECT imaging SPECT SCAN SPET ST tomography, emission computed, single photon Tomography, Emission-Computed, Single-Photon L-001079038 MSK-390 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Eligibility Criteria

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Inclusion Criteria

* Documented histologically confirmed adenocarcinoma of the prostate.
* Patient must have evidence of castration resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 \[PCWG3\] criteria) and a castrate serum testosterone level (i.e., ≤ 50 mg/dL).
* PSMA SUVmean \< 10 as determined by 68Ga-PSMA-11 PET.
* Patients must have received a next-generation androgen receptor-signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide, darolutamide). There must be at least a 2-week washout period after stopping these agents. Patients should be weaned off steroids at least 1 week prior to starting treatment.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT and/or bone scan and is suitable for repeated assessment.
* Hemoglobin ≥ 10 g/dL (measured within 28 days prior to administration of study treatment)
* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (measured within 28 days prior to administration of study treatment)
* Platelet count ≥ 100 x 10\^9/L (measured within 28 days prior to administration of study treatment)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
* Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN (measured within 28 days prior to administration of study treatment) . For patients with known Gilbert's Syndrome they must be ≤ 3 x ULN (measured within 28 days prior to administration of study treatment)
* Calculated creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula) (measured within 28 days prior to administration of study treatment)
* Patients and their partners, who are sexually active and of childbearing potential must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 3 months after last dose of study drug to prevent pregnancy in a partner.
* Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.

Exclusion Criteria

* Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition that could interfere with patient safety or provision of informed consent to participate in this study.
* Evidence of metastatic neuroendocrine/small cell prostate cancer (NEPC). Note: baseline biopsy is not required but is strongly encouraged if a patient is found to have an FDG-positive/PSMA-negative lesion on baseline imaging.
* Patients receiving any systemic therapy (aside from an luteinizing hormone-releasing hormone \[LHRH\] analogue) or radiotherapy within 2 weeks prior to study treatment.
* Any previous treatment with an HDAC inhibitor (including valproic acid) or 177Lu-PSMA-617.
* Persistent toxicities (CTCAE grade \>2) from prior cancer therapy, excluding alopecia and stable neuropathy.
* Patients considered a poor medical risk due to a serious, uncontrolled medical disorder or active, uncontrolled infection. Examples include, but are not limited to uncontrolled seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
* Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count \< 200.
* Patients with known active hepatitis (i.e. Hepatitis B or C). Prior Hep C infection is allowed as long as polymerase chain reaction (PCR) is negative.
* Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
* Deep vein thrombosis or pulmonary embolism diagnosed within the past six months.
* Active use of coumarin-derived anticoagulant medication (i.e. warfarin).
* Serious cardiac disorder, including but not limited to uncontrolled ventricular arrhythmia, recent (within 12 months) myocardial infarction, resting electrocardiogram (ECG) indicating Fridericia's corrected QT interval prolongation \> 500ms, or congenital long QT syndrome.
Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis

INDUSTRY

Sponsor Role collaborator

Institute for Prostate Cancer Research (IPCR)

UNKNOWN

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Schweizer

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michael Schweizer

Role: CONTACT

206-606-6252

Facility Contacts

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Michael Schweizer

Role: primary

206-606-6252

Other Identifiers

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NCI-2023-08921

Identifier Type: REGISTRY

Identifier Source: secondary_id

FHIRB0020244

Identifier Type: OTHER

Identifier Source: secondary_id

R37CA286450

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RG1123920

Identifier Type: -

Identifier Source: org_study_id

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