PSMA PET Scan-Directed Therapy for Prostate Cancer

Recruiting at 1 trial location

Overseen By Jane Romani

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Washington

Disqualifiers: Hepatitis B or C, Non-prostate malignancy, 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

Compensation: Varies

Number of Visits: 15

Duration: 24 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of advanced imaging techniques, such as PSMA or fluciclovine PET/CT scans, in guiding prostate cancer treatment. The researchers aim to determine if these scans can detect cancer early and help tailor treatments for areas with abnormalities. The treatments under investigation include surgery, radiotherapy, and medications like abiraterone (Zytiga or Yonsa, a hormone therapy) and prednisone (a corticosteroid). Men who have undergone surgery and radiation for prostate cancer and have rising PSA levels (a blood marker indicating cancer activity) might be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abiraterone and prednisone are usually well-tolerated by people with prostate cancer. In past studies, patients who took these medications lived longer than those who did not. Although some serious side effects occurred, they were less frequent in those taking abiraterone compared to standard treatments. This suggests that abiraterone and prednisone are generally safe options for patients. However, discussing any concerns with a doctor before starting a new treatment is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores PSMA PET scan-directed therapy, a cutting-edge approach for prostate cancer treatment. Unlike traditional treatments that might not effectively pinpoint cancer spread, this method uses advanced imaging techniques, like fluciclovine or PSMA PET/CT scans, to accurately detect and target metastatic regions. This precision enables more focused interventions, such as surgery or radiation, and optimizes the use of medications like abiraterone acetate and prednisone. The trial aims to assess whether this targeted strategy can improve outcomes by better managing the spread of disease, potentially leading to more personalized and effective treatment plans for patients.

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

Research has shown that abiraterone acetate, especially when combined with prednisone, can extend the lives of prostate cancer patients. This trial studies this combination, with some participants receiving only abiraterone acetate and prednisone, while others receive it alongside surgery or radiotherapy. This combination benefits patients who haven't undergone chemotherapy and those previously treated with docetaxel. Studies also suggest that even lower doses of abiraterone can control cancer in patients with metastatic prostate cancer. Specifically, evidence from trials like the STAMPEDE study confirmed that abiraterone extends survival in patients with high-risk prostate cancer. This indicates that the treatment is promising for effectively managing prostate cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Evan Yu

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Men who've had prostate surgery and radiation, with a recent PSA level between 0.2-10 ng/mL that's rising, but no visible metastasis on scans. They should be relatively healthy (ECOG 0 or 1), have certain blood levels within range, and not have other serious illnesses or recent cancers besides non-melanoma skin cancer.

Inclusion Criteria

Hemoglobin >= 9 g/dL

Absolute neutrophil count (ANC) >= 1.0 X 10^9/L

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have ongoing hepatitis B or C.

Patient with a serious underlying medical condition that would otherwise impair the patient's ability to undergo fluciclovine or PSMA PET/CT imaging or receive subsequent treatment

I am mentally capable of understanding and giving informed consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Assessment

Patients undergo fluciclovine or PSMA PET/CT to assess the presence of metastatic disease

1 week

1 visit (in-person)

Treatment

Patients receive abiraterone acetate and prednisone, with possible lymphadenectomy or radiation therapy for those with ≤ 3 regions of metastatic disease

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

121 weeks

8 visits (in-person)

Long-term Follow-up

Annual follow-up visits to monitor long-term outcomes

Annually after 66 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Abiraterone Acetate
• Prednisone
• PSMA PET Scan

Trial Overview

The trial is testing if targeted therapy directed by PSMA or fluciclovine PET/CT scans can effectively treat prostate cancer recurrences. It involves drugs like Abiraterone Acetate with Prednisone, potential lymph node removal, and possibly radiation based on scan results.

How Is the Trial Designed?

Group I: Group III (abiraterone, prednisone) Experimental Treatment 6 Interventions

Patients undergo fluciclovine or PSMA PET/CT and who have \> 3 regions of metastatic disease receive abiraterone acetate and prednisone as in Group II.

Group II: Group II (surgery, radiotherapy, abiraterone, prednisone) Experimental Treatment 8 Interventions

Patients undergo fluciclovine or PSMA PET/CT and who have =\< 3 regions of metastatic disease outside of the prostatic fossa that are amenable to metastasis-directed therapy undergo lymphadenectomy or radiation therapy. Six to ten weeks after surgery, patients receive abiraterone acetate 1000 mg PO QD and prednisone PO QD. Treatment repeats every 4 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may start radiation therapy after 2 cycles of abiraterone acetate and prednisone.

Group III: Group I (fluciclovine PET/CT) Active Control 3 Interventions

Patients for whom initial fluciclovine or PSMA PET/CT does not reveal any abnormalities outside the prostatic fossa undergo PSA rechecks every 3 months, and undergo fluciclovine or PSMA PET/CT once PSA is \> 2 ng/ml. If still no abnormalities are found outside of the prostatic fossa, patients continue to undergo PSA rechecks every 3 months, and undergo fluciclovine or PSMA PET/CT once PSA is \> 5 ng/ml. Patients are off study for treatment plan once PSA reaches 10 ng/ml.

Abiraterone is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Blue Earth Diagnostics

Industry Sponsor

Trials

43

Recruited

3,100+

Published Research Related to This Trial

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[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]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

In a study of 113 recurrent prostate cancer patients, those who received second-line PSMA-guided metastases-directed therapy (MDT) showed significantly higher metastases-free survival (MFS) and castration-resistant prostate cancer-free survival (CRPC-FS) compared to those who received conventional treatment.

While progression-free survival (PFS) was similar between the MDT and conventional treatment groups, MDT was identified as a strong predictor of MFS, highlighting its potential effectiveness in managing oligo-recurrent prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment. Bianchi, L., Ceci, F., Balestrazzi, E., et al.[2023]

Abiraterone acetate (Zytiga®) is an effective antiandrogen for prostate cancer but has poor oral bioavailability (<10%) and requires patients to fast around its administration due to a significant food effect (5-10-fold increase in absorption).

The review highlights the need for improved oral formulation strategies to enhance solubility and bioavailability of abiraterone acetate, aiming to reduce the required dose and eliminate the food effect, which could lead to better patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Schultz, HB., Meola, TR., Thomas, N., et al.[2020]

A 64-year-old man with prostate cancer showed a clear response in bone metastases after receiving Ra therapy, as evidenced by Ga-PSMA PET scans taken before and 4 weeks after treatment.

The patient's increasing PSA levels under abiraterone acetate therapy suggest that Ra therapy may be an effective option for managing advanced prostate cancer in cases where other treatments are not sufficient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer. Ahmadzadehfar, H., Schlenkhoff, CD., Rogenhofer, S., et al.[2021]

In a study of 104 patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate, the median overall survival was 16.4 months, highlighting the drug's effectiveness in this patient population.

Key prognostic factors for overall survival included early PSA response (greater than 30% decline at four weeks) and ECOG performance status, suggesting that these metrics can help identify patients who are more likely to benefit from abiraterone acetate treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate. España, S., Ochoa de Olza, M., Sala, N., et al.[2022]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

In a phase II study involving 41 men with metastatic castration-resistant prostate cancer, increasing the dose of abiraterone acetate from 1000 mg to 2000 mg daily did not result in any significant clinical benefit, as no patients showed a prostate-specific antigen (PSA) decline of 30% or more after 12 weeks.

The study found that factors such as lower baseline circulating androgen levels and individual differences in drug metabolism may contribute to resistance against standard-dose abiraterone therapy, suggesting that simply increasing the dose is not an effective strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Friedlander, TW., Graff, JN., Zejnullahu, K., et al.[2018]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

Prostate-specific membrane antigen (PSMA) is a key target for imaging and treating prostate cancer, with new small molecule peptides enabling high-quality PET imaging and targeted radionuclide therapy.

Early clinical studies of Lutetium 177 (Lu) PSMA therapy show promising safety and efficacy, with many men with metastatic prostate cancer responding positively even after failing other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. Emmett, L., Willowson, K., Violet, J., et al.[2022]

In a study of 30 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors, PSMA PET/CT imaging was found to be a valuable tool for assessing treatment response and predicting overall survival, with significant differences in survival between PSMA responders and nonresponders (54 months vs. 22 months).

The study showed strong correlations between PSMA-based and PSA-based responses, indicating that both imaging and blood tests can effectively evaluate treatment efficacy, and both PSMA response criteria (EAU/EANM and RECIP 1.0) performed similarly in predicting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA PET/CT for Response Assessment and Overall Survival Prediction in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors. Shagera, QA., Karfis, I., Kristanto, P., et al.[2023]

Abiraterone acetate significantly improves overall survival and radiographic progression-free survival in men with metastatic castration-resistant prostate cancer (CRPC) when combined with prednisone, based on results from a multinational phase III study involving men who had previously received docetaxel.

The treatment is generally well-tolerated, although it can cause side effects like hypokalaemia and hypertension; however, serious adverse events were relatively low in the phase III studies, indicating it is a viable option for managing metastatic CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. Hoy, SM.[2021]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/33826036/

Real-World Safety and Efficacy Outcomes with Abiraterone ...

Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1130634325001023

Low-dose abiraterone acetate for the treatment of prostate ...

This study provides evidence supporting the use of low-dose abiraterone in patients with metastatic prostate cancer, showing survival and ...

3.

ecancer.org

ecancer.org/en/news/26791-lower-dose-of-abiraterone-acetate-as-effective-for-prostate-cancer-treatment

Lower dose of abiraterone acetate as effective for prostate ...

In their study involving nine men with metastatic prostate cancer, they found that this lower dose resulted in comparable cancer suppression.

4.

ascopubs.org

ascopubs.org/doi/abs/10.1200/JCO.2025.43.5_suppl.367

Real-world discontinuation and efficacy data of abiraterone ...

Background: Data from STAMPEDE trial confirmed Overall survival benefit for patients with high-risk localized or locally advanced prostate ...

5.

nature.com

nature.com/articles/s41391-024-00816-0

Real-world overall survival with abiraterone acetate versus ...

There are no large head-to-head phase 3 clinical trials comparing overall survival (OS) for abiraterone and enzalutamide.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30987939/

Abiraterone acetate plus prednisone in patients with newly ...

The combination of abiraterone acetate plus prednisone with ADT was associated with significantly longer overall survival than placebos plus ADT in men with ...

7.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1704174

Abiraterone plus Prednisone in Metastatic, Castration- ...

The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group ( ...

8.

zytigahcp.com

zytigahcp.com/efficacy-and-safety/

Metastatic High-Risk CSPC LATITUDE Study

ZYTIGA + prednisone demonstrated a statistically significant improvement in OS, based on a pre-specified interim analysis, compared to placebos.

9.

mdpi.com

mdpi.com/2072-6694/17/17/2747

The Safety of Abiraterone Acetate in Patients with ...

More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent ...