Hormonal Therapy Impact on PSMA Expression in Prostate Cancer

Overseen By Lauren Drake

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: OHSU Knight Cancer Institute

Must be taking: Hormonal therapy

Must not be taking: Supplements, Herbal medications

Disqualifiers: Uncontrolled infection, Intercurrent illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how hormonal therapy affects a protein called PSMA, linked to prostate cancer, and whether this alters cancer staging. It tests a treatment called Piflufolastat (also known as Pylarify, a diagnostic imaging agent) and involves two groups: those with prostate cancer that still responds to therapy (CSPC) and those whose cancer does not (CRPC). The goal is to determine the best timing for a special scan (PSMA PET) that helps doctors assess cancer response to treatment. Men with confirmed prostate cancer who are about to start hormonal therapy may be suitable for this study. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications. However, if you are on continuous ADT (androgen deprivation therapy), you will continue it if you have castration-resistant prostate cancer. It's best to discuss your specific medications with the trial team.

What is the safety track record for these treatments?

Research has shown that Piflufolastat, a drug used to help doctors see prostate cancer in scans, is generally safe and well-tolerated. The FDA has already approved it for this purpose, supporting its safety. Available safety information indicates that Piflufolastat rarely causes serious side effects. Some people might experience mild reactions like headaches or tiredness, but these are uncommon. This makes it a reasonably safe option for detecting and monitoring prostate cancer. Overall, Piflufolastat is a reliable choice for imaging prostate cancer, with a strong safety record. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the use of Piflufolastat in prostate cancer treatment because it offers a unique approach to imaging through the 18F-DCFPyL PET scan. Unlike standard treatments that primarily focus on reducing tumor size or slowing cancer progression, this method enhances the visualization of prostate-specific membrane antigen (PSMA) expression in cancer cells, which can provide more precise insights into the effectiveness of hormonal therapies. This advanced imaging technique could potentially lead to more tailored and effective treatment plans for patients with castration-resistant prostate cancer (CRPC) and castration-sensitive prostate cancer (CSPC).

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research shows that piflufolastat F 18 effectively images prostate cancer, boosting doctors' confidence in treatment planning in 96% of cases. This imaging agent highlights a protein called prostate-specific membrane antigen (PSMA), making cancerous areas easier to see. It is already approved in the U.S. for prostate cancer imaging. The trial will involve two separate cohorts: Cohort 1 with patients having castration-resistant prostate cancer (CRPC) and Cohort 2 with patients having castration-sensitive prostate cancer (CSPC). The trial aims to understand how hormonal therapy affects PSMA levels in prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Nadine Mallak, M.D.

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men aged 18 or older with confirmed prostate adenocarcinoma, who show PSMA uptake on initial scans and are about to start hormonal therapy. It includes those with castration sensitive (CSPC) or resistant (CRPC) prostate cancer, but excludes anyone who's had recent cancer treatment or started supplements/herbal meds aimed at treating cancer.

Inclusion Criteria

My prostate cancer responds to hormone therapy, and I haven't used hormone-targeting treatments in the last year.

My prostate cancer shows on a PSMA PET scan.

My prostate cancer diagnosis was confirmed through a tissue examination.

Exclusion Criteria

I do not have any serious infections that are not under control.

Intercurrent illness or condition that would limit compliance with study requirements

I haven't started any new cancer treatments or supplements between my two PSMA PET scans.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants receive a baseline PSMA PET scan prior to the start of hormonal therapy

1 day

1 visit (in-person)

Treatment

Participants receive hormonal therapy and undergo PSMA PET scans at 8 days and 28 days post-therapy initiation

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Biospecimen Collection
• Electronic Health Record Review
• Piflufolastat
• Positron Emission Tomography/Computed Tomography
• Positron Emission Tomography/Magnetic Resonance Imaging

Trial Overview The study is examining how hormone therapy affects PSMA levels in prostate cancer patients and if this changes tumor staging post-therapy. Participants will undergo PSMA PET/MRI or CT scans before and after starting hormonal treatments to track these changes.

How Is the Trial Designed?

Group I: Cohort 2: CSPC Experimental Treatment 5 Interventions

Patients with CSPC will receive 18F-DCFPyL PET prior to start of therapy (standard of care), then again 8 days and 28 days after initiation of hormonal therapy.

Group II: Cohort 1: CRPC Experimental Treatment 5 Interventions

Patients with CRPC will receive 18F-DCFPyL PET prior to start of therapy (standard of care), then again 8 days and 28 days after initiation of hormonal therapy.

Piflufolastat is already approved in United States, European Union for the following indications:

Approved in United States as Pylarify for:

• Positron emission tomography (PET) imaging in men with prostate-specific membrane antigen (PSMA)-positive lesions

Approved in European Union as Pylarify for:

• Positron emission tomography (PET) imaging in men with prostate-specific membrane antigen (PSMA)-positive lesions

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Progenics Pharmaceuticals, Inc.

Industry Sponsor

Trials

35

Recruited

4,400+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Progenics Pharmaceuticals, Inc., a Lantheus company

Collaborator

Trials

1

Recruited

80+

Published Research Related to This Trial

In castration-resistant prostate cancer (CRPC), prostate-specific membrane antigen (PSMA) expression can be lost in 15-20% of cases, particularly in liver lesions, indicating that the tumor microenvironment may influence PSMA levels.

The study identified HOXB13 as a key regulator of PSMA expression, which varies between androgen receptor-positive and negative CRPC, suggesting that understanding these mechanisms could help in selecting appropriate PSMA-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer. Bakht, MK., Yamada, Y., Ku, SY., et al.[2023]

Knocking down PSMA in LNCaP prostate cancer cells significantly decreased the activation of the Akt signaling pathway, indicating that PSMA may regulate this pathway and influence cancer cell behavior.

Both PSMA knockdown and treatment with the PI3K inhibitor LY294002 led to reduced cell proliferation, migration, and survival, suggesting that targeting the PI3K/Akt pathway could be a potential therapeutic strategy in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate specific membrane antigen knockdown impairs the tumorigenicity of LNCaP prostate cancer cells by inhibiting the phosphatidylinositol 3-kinase/Akt signaling pathway. Guo, Z., Lai, Y., Du, T., et al.[2018]

In men with hormone-sensitive prostate cancer, androgen blockade treatment led to a significant reduction in PSMA PET imaging signals (SUVmax) by day 9, with a 30% median decrease and a 100% PSA response rate, indicating effective early treatment response.

Conversely, in men with castrate-resistant prostate cancer, androgen blockade resulted in a 45% increase in PSMA PET imaging signals by day 9, suggesting a different response pattern that may complicate treatment planning and interpretation of imaging results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade. Emmett, L., Yin, C., Crumbaker, M., et al.[2021]

Piflufolastat F 18 (PYLARIFY®) is a newly approved diagnostic imaging agent that targets prostate-specific membrane antigen (PSMA) for use in PET scans, specifically for detecting prostate cancer lesions.

Approved in the USA on May 27, 2021, Piflufolastat F 18 is intended for men with prostate cancer who have suspected metastasis or recurrence, providing a valuable tool for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Piflufolastat F 18: Diagnostic First Approval. Keam, SJ.[2022]

18F-DCFPyL (piflufolastat F 18) is the first PSMA-targeted PET agent approved for imaging prostate cancer, demonstrating high affinity for PSMA and becoming the standard-of-care for primary staging and recurrent disease.

The approval of 18F-DCFPyL was based on two significant multi-center trials, OSPREY and CONDOR, which focused on high-risk primary staging and biochemical recurrence, respectively, highlighting its efficacy in identifying prostate cancer metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image acquisition and interpretation of 18F-DCFPyL (piflufolastat F 18) PET/CT: How we do it. Rowe, SP., Voter, AF., Werner, RA., et al.[2023]

The 18F-labeled PSMA-directed PET agent [18F]DCFPyL (PYLARIFY) has shown significant clinical utility in staging and restaging prostate cancer, supported by major trials like OSPREY and CONDOR.

Following its recent FDA approval, [18F]DCFPyL is expected to see increased adoption for imaging and management of prostate cancer, enhancing image-guided treatment strategies in both the U.S. and Europe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]DCFPyL PET/CT for Imaging of Prostate Cancer. Rowe, SP., Buck, A., Bundschuh, RA., et al.[2022]

The new PET agent 18F-DCFPyL, which targets prostate-specific membrane antigen (PSMA), has shown superior diagnostic accuracy compared to conventional imaging methods for staging and restaging prostate cancer, as demonstrated in the OSPREY and CONDOR clinical trials.

The use of PSMA-PET imaging is expected to significantly enhance prostate cancer management and may lead to new diagnostic and therapeutic opportunities, improving overall patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Piflufolastat F-18 (18F-DCFPyL) for PSMA PET imaging in prostate cancer . Voter, AF., Werner, RA., Pienta, KJ., et al.[2022]

In a study of 235 patients undergoing F-18 PSMA PET imaging for prostate cancer, 65.5% had PSMA-avid lesions detected, indicating its effectiveness in identifying cancer spread.

The imaging led to changes in treatment plans for 54.5% of patients in the initial staging group and 33.9% in the biochemical recurrence group, demonstrating its significant impact on clinical decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of piflufolastat F-18 PSMA PET imaging on clinical decision-making in prostate cancer across disease states: A retrospective review. Arafa, AT., Jain, A., Skrobanek, P., et al.[2023]

In a study of 52 patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing docetaxel (DTX) therapy, high PSMA-derived tumor volume (TV-PSMA) was found to significantly predict treatment failure, with patients having a TV-PSMA greater than 107 cm³ being 8.2 times more likely to experience DTX failure.

The research indicates that PSMA-based tumor burden measurements can serve as reliable predictive tools for overall survival (OS) and time to progression (TTP) in mCRPC patients, highlighting the importance of assessing tumor burden before initiating DTX therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can PSMA-based tumor burden predict response to docetaxel treatment in metastatic castration-resistant prostate cancer? Has Simsek, D., Kuyumcu, S., Karadogan, S., et al.[2021]

In a study of 26 metastatic castration-resistant prostate cancer patients treated with enzalutamide or abiraterone, changes in Prostate-Specific Membrane Antigen (PSMA) expression on PET/CT scans were strongly associated with treatment response, indicating that PSMA PET/CT can be a reliable tool for monitoring efficacy.

All patients who responded to treatment also showed a decrease in PSMA expression, while non-responders had stable or increased PSMA levels, suggesting that PSMA expression changes can effectively predict patient outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients. Plouznikoff, N., Artigas, C., Sideris, S., et al.[2021]

Enzalutamide treatment significantly increases PSMA expression in prostate cancer cell lines and tumors, which could make patients with low PSMA levels eligible for PSMA-directed radioligand therapy (RLT).

In a study involving human prostate cancer cell lines and a mouse model, enzalutamide treatment led to a notable increase in PSMA levels, as confirmed by PET/CT imaging, suggesting a potential strategy to enhance the effectiveness of RLT in metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. Staniszewska, M., Fragoso Costa, P., Eiber, M., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37934376/

Cost-Effectiveness Modeling of Prostate-Specific ... Results: Over a lifetime horizon, piflufolastat F 18 had the greatest effectiveness in terms of LYs (6.80) and QALYs (5.33); for the comparators ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.41

The role of conventional imaging and piflufolastat F18 in ... Across both cohorts, clinicians rated improvement in treatment planning confidence following 96% of piflufolastat F18 scans. Conclusions: ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10811023/

Cost-Effectiveness Modeling of Prostate-Specific Membrane ... This study suggests that piflufolastat F 18 is a cost-effective diagnostic option for men with prostate cancer in the US, with higher associated LY, QALY, and ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT375362

Piflufolastat f 18-PET/CT in patients with prostate cancer Daro-PET: A phase 2 trial of darolutamide as a prostate-specific membrane antigen (PSMA) expression enhancer in patients with localized prostate cancer.

5. urologytimes.com urologytimes.com/view/fda-accepts-nda-for-new-formulation-of-piflufolastat-f-18-in-prostate-cancer

FDA accepts NDA for new formulation of piflufolastat F 18 ... Piflufolastat F 18 injection was approved in the US in May 2021 2 based on data from the phase 3 OSPREY (NCT02981368) and CONDOR (NCT03739684) ...

6. pylarify.com pylarify.com/efficacy-safety/safety

Explore PYLARIFY® Safety Data & Side Effects PYLARIFY is a PSMA-targeted PET imaging agent for prostate cancer. Learn more about PYLARIFY safety data and adverse reactions.

7. pylarify.com pylarify.com/safety-old

Explore PYLARIFY® Safety Data & Side Effects PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/214793s000lbl.pdf

PYLARIFY® (piflufolastat F 18) injection, for intravenous use PYLARIFY uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05712473?term=AREA%5BBasicSearch%5D(PYLARIFY)&rank=1

Study Details | NCT05712473 | An Observational Registry ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

10. mayoclinic.org mayoclinic.org/drugs-supplements/piflufolastat-f-18-intravenous-route/description/drg-20516701

Piflufolastat f 18 (intravenous route) - Side effects & uses Piflufolastat F 18 injection is used with a PET scan (positron emission tomography) of prostate-specific membrane antigen (PSMA) positive lesions in men with ...