- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06145633
Vorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer
Vorinostat to Augment Response to Lutetium-PSMA-617 in the Treatment of Patients With PSMA-Low Metastatic Castration-Resistant Prostate Cancer
Study Overview
Status
Conditions
Intervention / Treatment
- Procedure: Biopsy
- Procedure: Single Photon Emission Computed Tomography
- Other: Gallium Ga 68 Gozetotide
- Procedure: Bone Scan
- Other: Fludeoxyglucose F-18
- Procedure: Biospecimen Collection
- Procedure: Computed Tomography
- Drug: Lutetium Lu 177 Vipivotide Tetraxetan
- Procedure: Positron Emission Tomography
- Drug: Vorinostat
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 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 single photon emission computed tomography (SPECT)/CT and fludeoxyglucose F-18 (FDG) PET/CT during screening and 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Michael Schweizer
- Phone Number: 206-606-6252
- Email: schweize@uw.edu
Study Locations
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
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Principal Investigator:
- Michael Schweizer
-
Contact:
- Michael Schweizer
- Phone Number: 206-606-6252
- Email: schweize@uw.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
- 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.
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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 SPECT/CT and FDG PET/CT during screening and on trial.
Patients undergo blood sample collection on trial and may also optionally undergo biopsy during screening and on trial.
|
Undergo biopsy
Other Names:
Undergo SPECT/CT
Other Names:
Given IV
Other Names:
Undergo bone scan
Other Names:
Undergo FDG PET/CT
Other Names:
Undergo blood sample colleciton
Other Names:
Undergo CT, SPECT/CT, PET/CT
Other Names:
Given 177Lu-PSMA-617
Other Names:
Undergo 68Ga-PSMA-11 PET
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients who convert from prostate-specific membrane antigen (PSMA) low to PSMA high
Time Frame: Up to 40 weeks
|
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).
|
Up to 40 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective radiographic response rate
Time Frame: Up to 2 years
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Will be determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
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Up to 2 years
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Prostate specific antigen (PSA)50 response rate
Time Frame: Baseline up to 2 years
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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.
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Baseline up to 2 years
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Progression free survival (PFS)
Time Frame: From the start of treatment until disease progression, clinical progression, or death, whichever occurs first, assessed up to 2 years
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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.
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From the start of treatment until disease progression, clinical progression, or death, whichever occurs first, assessed up to 2 years
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PSA PFS
Time Frame: From the start of treatment until PSA progression, assessed up to 2 years
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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.
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From the start of treatment until PSA progression, assessed up to 2 years
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Overall survival
Time Frame: From the start of treatment until death from any cause, assessed up to 2 years
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Will be estimated using Kaplan-Meier method.
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From the start of treatment until death from any cause, assessed up to 2 years
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Number of discrete lesions
Time Frame: Up to 40 weeks
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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.
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Up to 40 weeks
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Absolute change in PSMA standardized uptake value (SUV) mean
Time Frame: Up to 40 weeks
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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.
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Up to 40 weeks
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Incidence of adverse events
Time Frame: Up to 2 years
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Will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Event version 5.0 guidelines.
|
Up to 2 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael Schweizer, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites
- Antineoplastic Agents
- Radiopharmaceuticals
- Anticoagulants
- Chelating Agents
- Sequestering Agents
- Histone Deacetylase Inhibitors
- Calcium Chelating Agents
- Fluorodeoxyglucose F18
- Vorinostat
- Edetic Acid
- Gallium 68 PSMA-11
- Deoxyglucose
- 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
- Pluvicto
Other Study ID Numbers
- RG1123920
- NCI-2023-08921 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- FHIRB0020244 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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