Trial Title:
Vorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer
NCT ID:
NCT06145633
Condition:
Castration-Resistant Prostate Carcinoma
Metastatic Prostate Adenocarcinoma
Stage IVB Prostate Cancer AJCC v8
Conditions: Official terms:
Prostatic Neoplasms
Deoxyglucose
Vorinostat
Edetic Acid
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Fluorodeoxyglucose F18
Gallium 68 PSMA-11
Pluvicto
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample colleciton
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
Bone Scintigraphy
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT, SPECT/CT, PET/CT
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Other
Intervention name:
Fludeoxyglucose F-18
Description:
Undergo FDG PET/CT
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
18FDG
Other name:
FDG
Other name:
Fludeoxyglucose (18F)
Other name:
fludeoxyglucose F 18
Other name:
Fludeoxyglucose F18
Other name:
Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
Other name:
Fluorodeoxyglucose F18
Intervention type:
Other
Intervention name:
Gallium Ga 68 Gozetotide
Description:
Given IV
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
(68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC
Other name:
(68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC
Other name:
(68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC
Other name:
(68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC
Other name:
(68Ga)Glu-urea-Lys(Ahx)-HBED-CC
Other name:
68Ga-DKFZ-PSMA-11
Other name:
68Ga-HBED-CC-PSMA
Other name:
68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC
Other name:
68Ga-PSMA
Other name:
68Ga-PSMA-11
Other name:
68Ga-PSMA-HBED-CC
Other name:
[68Ga] Prostate-specific Membrane Antigen 11
Other name:
[68Ga]GaPSMA-11
Other name:
AAA 517
Other name:
AAA-517
Other name:
AAA517
Other name:
Ga PSMA
Other name:
Ga-68 labeled DKFZ-PSMA-11
Other name:
Ga-68 labeled PSMA-11
Other name:
GA-68 PSMA-11
Other name:
Gallium Ga 68 PSMA-11
Other name:
Gallium Ga 68-labeled PSMA-11
Other name:
GALLIUM GA-68 GOZETOTIDE
Other name:
Gallium-68 PSMA
Other name:
Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC
Other name:
GaPSMA
Other name:
PSMA-HBED-CC GA-68
Intervention type:
Drug
Intervention name:
Lutetium Lu 177 Vipivotide Tetraxetan
Description:
Given 177Lu-PSMA-617
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
177Lu-labeled PSMA-617
Other name:
177Lu-PSMA-617
Other name:
AAA 617
Other name:
AAA-617
Other name:
AAA617
Other name:
Lu177-PSMA-617
Other name:
Lutetium Lu 177-PSMA-617
Other name:
LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN
Other name:
Lutetium-177-PSMA-617
Other name:
Pluvicto
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo 68Ga-PSMA-11 PET
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Procedure
Intervention name:
Single Photon Emission Computed Tomography
Description:
Undergo SPECT/CT
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
Medical Imaging, Single Photon Emission Computed Tomography
Other name:
Single Photon Emission Tomography
Other name:
Single-Photon Emission Computed
Other name:
single-photon emission computed tomography
Other name:
SPECT
Other name:
SPECT imaging
Other name:
SPECT SCAN
Other name:
SPET
Other name:
ST
Other name:
tomography, emission computed, single photon
Other name:
Tomography, Emission-Computed, Single-Photon
Intervention type:
Drug
Intervention name:
Vorinostat
Description:
Given IV
Arm group label:
Treatment (vorinostat, 177Lu-PSMA-617)
Other name:
L-001079038
Other name:
MSK-390
Other name:
SAHA
Other name:
Suberanilohydroxamic Acid
Other name:
Suberoylanilide Hydroxamic Acid
Other name:
Zolinza
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). 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.
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.
Criteria for 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.
- 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.
Gender:
Male
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fred Hutch/University of Washington Cancer Consortium
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michael Schweizer
Phone:
206-606-6252
Email:
schweize@uw.edu
Investigator:
Last name:
Michael Schweizer
Email:
Principal Investigator
Start date:
September 18, 2024
Completion date:
December 30, 2027
Lead sponsor:
Agency:
University of Washington
Agency class:
Other
Collaborator:
Agency:
Novartis
Agency class:
Industry
Collaborator:
Agency:
Institute for Prostate Cancer Research (IPCR)
Agency class:
Other
Source:
University of Washington
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06145633
