RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-09-18

Study Completion:2027-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06145633

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * Patients must have received at least one taxane chemotherapy regimen. * 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.	* 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.

Inclusion Criteria

Exclusion 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.
* Patients must have received at least one taxane chemotherapy regimen.
* 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.

* 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.

Contacts and Locations

Study Contact

Michael Schweizer

CONTACT

206-606-6252

schweize@uw.edu

Principal Investigator

Michael Schweizer

PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: University of Washington

Michael Schweizer, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-18

Study Completion Date2027-12-30

Study Record Updates

Study Start Date2024-09-18

Study Completion Date2027-12-30

Terms related to this study

Additional Relevant MeSH Terms

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