PSMA PET Scan-Directed Therapy for Prostate Cancer

Recruiting at 1 trial location

Overseen By Patrick Panlasigui

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

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well prostate specific membrane antigen (PSMA) or fluciclovine positron emission tomography (PET)/computed tomography (CT) site-directed therapy works for treating patients with prostate cancer. PSMA or fluciclovine PET/CT may detect prostate cancer early and may help to show whether patients benefit from site directed treatment to PET detected abnormalities.

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.

What data supports the effectiveness of the drug Abiraterone Acetate in treating prostate cancer?

Research shows that Abiraterone Acetate, when combined with prednisone, significantly prolongs survival and delays disease progression in patients with metastatic castration-resistant prostate cancer, compared to a placebo. ^{1 2 3 4 5}

Is abiraterone acetate safe for humans?

Abiraterone acetate, used with prednisone, is generally considered safe for treating metastatic castration-resistant prostate cancer, though it can cause side effects like low potassium levels, high blood pressure, fluid retention, and liver issues. In clinical trials, serious side effects were relatively rare. ^{3 4 6 7 8}

What makes the PSMA PET Scan-Directed Therapy with Abiraterone and Prednisone unique for prostate cancer?

This treatment is unique because it uses PSMA PET scans to guide therapy, allowing for precise targeting of prostate cancer cells, and combines abiraterone and prednisone to inhibit androgen production, which fuels prostate cancer growth. This approach is particularly beneficial for patients with metastatic castration-resistant prostate cancer, as it helps assess treatment response and predict overall survival. ^{9 10 11 12 13}

Research Team

Evan Yu

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Sweden 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. [2017]

2. New Zealand 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

4. United States 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. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. [2018]

6. Germany 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. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer. [2021]

11. United States 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. [2022]

12. Canada pubmed.ncbi.nlm.nih.gov

Image acquisition and interpretation of 18F-DCFPyL (piflufolastat F 18) PET/CT: How we do it. [2023]

13. United States 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. [2023]