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Castration-Resistant Prostate CarcinomaPhase 2NCT06145633

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

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Bone Scan in people with Castration-Resistant Prostate Carcinoma and Metastatic Prostate Adenocarcinoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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). Read more about this study

Who is it for?
Any age, men only
What is being tested?
Biopsy Procedure, Biospecimen Collection and Bone Scan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
18 Sep 2024to 30 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Michael Schweizer contact

206-606-6252

schweize@uw.edu

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Michael Schweizer, 206-606-6252, schweize@uw.edu

    Michael Schweizer

    Recruiting

Other trials in United States

About this study

Official title: Vorinostat to Augment Response to 177Lutetium-PSMA-617 in the Treatment of Patients With PSMA-Low Metastatic Castration-Resistant Prostate Cancer

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.

Read the detailed description

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.

Being tested
Biopsy Procedure, Biospecimen Collection, Bone Scan, Computed Tomography, Fludeoxyglucose F-18
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT, PET/CT, SPECT/CT

  • Fludeoxyglucose F-18Other

    Also called 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18

    Undergo FDG PET/CT

  • Gallium Ga 68 GozetotideOther

    Also called (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

    Given IV

  • Lutetium Lu 177 Vipivotide TetraxetanDrug

    Also called 177Lu-labeled PSMA-617, 177Lu-PSMA-617, AAA 617, AAA-617

    Given 177Lu-PSMA-617

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo 68Ga-PSMA-11 PET

  • Single Photon Emission Computed TomographyProcedure or surgery

    Also called Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, Single-Photon Emission Computed, single-photon emission computed tomography

    Undergo SPECT/CT

  • VorinostatDrug

    Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid

    Given IV

Study groups in NCT06145633
Study groupRoleWhat they receive
Treatment (vorinostat, 177Lu-PSMA-617)ExperimentalPatients 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Other: Gallium Ga 68 Gozetotide; Drug: Lutetium Lu 177 Vipivotide Tetraxetan; Procedure: Positron Emission Tomography; Procedure: Single Photon Emission Computed Tomography; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients who convert from prostate-specific membrane antigen (PSMA) low to PSMA high

    Will be calculated as the percentage with 95% confidence interval (CI) of the total number of patients who had PSMA-high expression on re-assessment gallium Ga 68 gozetotide (68Ga)-PSMA-11 positron emission tomography (PET).

    Measured: Up to 40 weeks

Secondary outcomes (8)

  1. Objective radiographic response rate

    Will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

    Measured: Up to 2 years

  2. Prostate specific antigen (PSA)50 response rate

    The percent decline in PSA compared to baseline (the PSA level prior to initiation of lutetium Lu 177 vipivotide tetraxetan will be calculated for each patient for every on-study PSA value obtained. PSA50 response will be defined as a decline in PSA ≥ 50% compared to baseline. Will be reported as a percentage with 95% CI.

    Measured: Baseline up to 2 years

  3. Progression free survival (PFS)

    Disease progression measured by modified RECIST criteria or Prostate Cancer Working Group 3 criteria for bone lesions and clinical progression as determined by the treating physician. Will be estimated using Kaplan-Meier method.

    Measured: From the start of treatment until disease progression, clinical progression, or death, whichever occurs first, assessed up to 2 years

  4. PSA PFS

    For patients showing an initial decline in PSA from baseline, PSA progression will be defined as an increase in PSA ≥ 25% and ≥ 2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later. For those with no decline in PSA from baseline, PSA progression will be defined as an increase in PSA that is ≥ 25% and ≥ 2ng/mL after 12 weeks. Will be estimated using Kaplan-Meier method.

    Measured: From the start of treatment until PSA progression, assessed up to 2 years

  5. Overall survival

    Will be estimated using Kaplan-Meier method.

    Measured: From the start of treatment until death from any cause, assessed up to 2 years

  6. Number of discrete lesions

    Will determine the number of discrete lesions on imaging converted from low to high PSMA expression across the study population at the time of re-assessment 68Ga-PSMA-11 PET.

    Measured: Up to 40 weeks

  7. Absolute change in PSMA standardized uptake value (SUV) mean

    PSMA SUVmean will be determined by an experienced nuclear medicine physician by measuring the PSMA SUV at each site of PSMA positive disease and dividing by the total PSMA positive tumor volume.

    Measured: Up to 40 weeks

  8. Incidence of adverse events

    Will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Event version 5.0 guidelines.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Nov 2023
  2. Study start18 Sep 2024
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion30 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06145633
Sponsor's protocol ID
RG1123920
Other IDs
NCI-2023-08921, FHIRB0020244, R37CA286450
Status last verified
Aug 2026
First submitted
17 Nov 2023
Last updated
6 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Bone Scan in people with Castration-Resistant Prostate Carcinoma and Metastatic Prostate Adenocarcinoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Michael Schweizer (206-606-6252, schweize@uw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients who convert from prostate-specific membrane antigen (PSMA) low to PSMA high (time frame: Up to 40 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06145633.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.

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