Clinical Trial · NCT06145633

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

Overview

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.

Sponsor

Fred Hutchinson Cancer Center

Phase

Phase 2

Contacts

Michael Schweizer (PRINCIPAL_INVESTIGATOR)

Michael Schweizer (CONTACT)

schweize@uw.edu

206-606-6252

ClinicalTrials.gov

NCT06145633

Drug / Compound

PSMA-617

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: DOTA

gozetotide

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: HBED-CC

FDG

Isotope(s):

Target(s):

Glucose Transport

Ligand Class: Small Molecules

Eligibility

Inclusion

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)
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
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).
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.
Platelet count ≥ 100 x 10\^9/L (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)
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.
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.
Documented histologically confirmed adenocarcinoma of the prostate.
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
PSMA SUVmean \< 10 as determined by 68Ga-PSMA-11 PET.
Calculated creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula) (measured within 28 days prior to administration of study treatment)
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
Hemoglobin ≥ 10 g/dL (measured within 28 days prior to administration of study treatment)

Exclusion

Any previous treatment with an HDAC inhibitor (including valproic acid) or 177Lu-PSMA-617.
Deep vein thrombosis or pulmonary embolism diagnosed within the past six months.
Patients receiving any systemic therapy (aside from an luteinizing hormone-releasing hormone \[LHRH\] analogue) or radiotherapy within 2 weeks prior to study treatment.
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.
Persistent toxicities (CTCAE grade \>2) from prior cancer therapy, excluding alopecia and stable neuropathy.
Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
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.
Active use of coumarin-derived anticoagulant medication (i.e. warfarin).
Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and a CD4 count \< 200.
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.
Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.