Using vorinostat and a radioactive treatment for low PSMA metastatic prostate cancer

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

This study is testing if adding vorinostat to a radioactive treatment can help people with low PSMA metastatic prostate cancer feel better and improve their outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sex: Male
• Sponsor: Fred Hutchinson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT06145633 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of vorinostat in treating patients with PSMA-low metastatic castration-resistant prostate cancer (mCRPC). Participants will take vorinostat orally for 28 days, followed by a PET scan and the option to receive 177Lu-PSMA-617, a targeted radioactive therapy. The treatment will be administered every six weeks for up to six cycles, with regular monitoring through imaging and blood tests. Patients will be followed for up to two years after treatment to assess outcomes.

Who should consider this trial

Good fit: Ideal candidates include men with histologically confirmed adenocarcinoma of the prostate who have evidence of castration-resistant disease and low PSMA levels.

Not a fit: Patients with localized prostate cancer or those who have not undergone prior treatments such as taxane chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with low PSMA expression in metastatic prostate cancer.

How similar studies have performed: Other studies have shown promise with PSMA-targeted therapies, but this specific combination approach is novel.

Eligibility criteria

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.

Where this trial is running

Seattle, Washington

• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Michael Schweizer — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Michael Schweizer

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