PSMA PET Scan-Directed Therapy for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Washington
Disqualifiers: Hepatitis B or C, Non-prostate malignancy, others
No Placebo Group
Prior Safety Data
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.
12345Is 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.
34678What 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.
910111213Eligibility 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.
+14 more
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.
+5 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Group III (abiraterone, prednisone)Experimental Treatment6 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 Treatment8 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 Control3 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Pittsburgh Cancer Institute (UPCI)Pittsburgh, PA
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
Blue Earth DiagnosticsIndustry Sponsor
References
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]In a randomized clinical trial (COU-AA-301), abiraterone acetate (Zytiga(®)) was shown to be superior to prednisone in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the value of abiraterone treatment for patients with mCRPC in clinical practice in Sweden is not known. The aim of this study was to compare the outcomes and treatment patterns of abiraterone treatment in a Swedish observational study to those of the pivotal clinical trial, thereby discussing the external validity of the postchemotherapy clinical trial from a Swedish perspective.
PSA Kinetics as Prognostic Markers of Overall Survival in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate. [2022]Abiraterone acetate (AA) is widely used in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, a significant percentage of patients will still progress, highlighting the need to identify patients more likely to benefit from AA. Parameters linked to prostate-specific antigen (PSA) kinetics are promising prognostic markers. We have examined clinical and PSA-related factors potentially associated with overall survival (OS) in patients treated with AA.
Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]Oral abiraterone acetate (Zytiga®), a selective cytochrome P450 17A1 enzyme inhibitor, is used in combination with prednisone or prednisolone to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel-containing chemotherapy. In a clinical trial in patients with CRPC, abiraterone acetate plus prednisone significantly prolonged overall survival, the time to prostate-specific antigen progression and progression-free survival compared with placebo plus prednisone.
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]On December 10, 2012, the U.S. Food and Drug Administration granted full approval for a modified indication for abiraterone acetate (Zytiga tablets; Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The approval was based on clinical trial COU-AA-302, which randomly allocated asymptomatic or mildly symptomatic patients with chemotherapy-naïve mCRPC and no visceral metastases to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N = 542). The coprimary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). The median rPFS was 8.3 months in the placebo arm and had not yet been reached in the abiraterone acetate arm {HR, 0.43 [95% confidence interval (CI) 0.35-0.52]; P
High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. [2018]Abiraterone acetate (AA) inhibits androgen biosynthesis and prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) when combined with prednisone (P). Resistance to therapy remains incompletely understood. In this open-label, single-arm, multicenter phase II study we investigated the clinical benefit of increasing the dose of AA at the time of resistance to standard-dose therapy.
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]Abiraterone acetate is a highly variable drug and has been approved for the treatment of patients with metastatic castration-resistant prostate cancer in many countries. This study was conducted to compare the pharmacokinetic profile between the test product (abiraterone acetate tablet) and reference product ZYTIGA® (250 mg) mainly.
Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]Abiraterone acetate, marketed as Zytiga®, is an antiandrogen medication used in the treatment of prostate cancer. Abiraterone acetate is a BCS Class IV compound associated with several oral delivery challenges. Its low solubility and high lipophilicity lead to poor oral bioavailability (
Abiraterone acetate: a review of its use in patients with metastatic castration-resistant prostate cancer. [2021]Abiraterone acetate (Zytiga(®)) is an orally administered, selective inhibitor of the 17α-hydroxylase and C17,20-lyase enzymatic activities of cytochrome P450 (CYP) 17. CYP17 is required for androgen biosynthesis, with androgen receptor signalling crucial in the progression from primary to metastatic prostate cancer. Abiraterone acetate is approved in the European Union and the US, in combination with prednisone or prednisolone, for the treatment of men with metastatic castration-resistant prostate cancer (CRPC). When administered in combination with prednisone in a placebo-controlled, multinational phase III study, abiraterone acetate significantly prolonged overall survival and radiographic progression-free survival (rPFS) in men with metastatic CRPC who had previously received docetaxel. In men with metastatic CRPC who had not previously received chemotherapy participating in a placebo-controlled, multinational phase III study, there was a strong trend towards an overall survival benefit, a significant prolongation in rPFS and significant delays in clinical decline, the need for chemotherapy and the onset of pain observed. Given the nature of the therapy, the overall tolerability profile of abiraterone acetate, in combination with prednisone, was acceptable in men with metastatic CRPC. Abiraterone acetate is associated with hypokalaemia, hypertension, and fluid retention or oedema, secondary to its mechanism of action, and with cardiac adverse events and hepatotoxicity; however, in the phase III studies the incidences of the most frequently reported grade 3 or 4 adverse events of special interest were relatively low. Although the final overall survival data in men with metastatic CRPC who have not previously received chemotherapy are awaited, current evidence indicates that abiraterone acetate is a useful option for the treatment of metastatic CRPC.
PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment. [2023]Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients.
68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer. [2021]A 64-year-old man with prostate cancer and an increasing prostate-specific antigen (PSA) level under therapy with abiraterone acetate underwent a therapy with Ra. Before the first therapy and 4 weeks after the last cycle, the patient underwent Ga-PSMA PET, which showed a clear response of bone metastases.
Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. [2022]Prostate-specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high-binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides. Early clinical studies evaluating the safety and efficacy of Lu PSMA therapy have demonstrated promising results with a significant proportion of men with metastatic prostate cancer, who have already failed other therapies, responding clinically to Lu PSMA. This review discusses the practical issues of administering Lu PSMA, and gives an overview of the findings from currently published trials in regards to treatment response rates, expected toxicities and safety.
Image acquisition and interpretation of 18F-DCFPyL (piflufolastat F 18) PET/CT: How we do it. [2023]Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is rapidly becoming widely accepted as the standard-of-care for imaging of men with prostate cancer. Labeled indications for regulatoryapproved agents include primary staging and recurrent disease in men at risk of metastases. The first commercial PSMA PET agent to become available was 18F-DCFPyL (piflufolastat F 18), a radiofluorinated small molecule with high-affinity for PSMA. The regulatory approval of 18F-DCFPyL hinged upon two key, multi-center, registration trials, OSPREY (patient population: highrisk primary staging) and CONDOR (patient population: biochemical recurrence). In this manuscript, we will (1) review key findings from the OSPREY and CONDOR trials, (2) discuss the clinical acquisition protocol we use for 18F-DCFPyL PET scanning, (3) present information on important pearls and pitfalls, (4) provide an overview of the PSMA reporting and data system (PSMA-RADS) interpretive framework, and (5) posit important future directions for research in PSMA PET. Our overall goal is to provide a brief introduction for practices and academic groups that are adopting 18F-DCFPyL PET scans for use in their patients with prostate cancer.
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]We aimed to evaluate the role of prostate-specific membrane antigen (PSMA) PET/CT for response assessment and outcome prediction in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs), including abiraterone acetate or enzalutamide. Methods: We retrospectively analyzed 30 ARPI-treated mCRPC patients who underwent 68Ga-PSMA-11 PET/CT within 8 wk before (baseline) and 12 ± 4 wk after treatment initiation. Total PSMA tumor volume was calculated using the fixed threshold method (SUV ≥ 3). Patients were categorized as PSMA responders (PSMA-Rs) or PSMA nonresponders (PSMA-NRs) on the basis of both European Association of Urology/European Association of Nuclear Medicine (EAU/EANM) criteria and Response Evaluation Criteria in PSMA PET/CT (RECIP) 1.0. PSMA-R included patients with a complete response, a partial response, or stable disease, and PSMA-NR included those with progressive disease. On the basis of prostate-specific antigen (PSA), patients were classified as biochemical responders if PSA decreased by at least 50% and as nonresponders if it did not. The Φ-coefficient was used to evaluate the correlation of PSMA- and PSA-based responses. Survival analysis was performed using the Cox regression hazard model and the Kaplan-Meier method. Predictive accuracy was tested for both response criteria. Results: On the basis of PSMA PET/CT, 13 (43%) patients were PSMA-NR according to the EAU/EANM criteria and 11 (37%) patients were PSMA-NR according to RECIP 1.0. Significant correlations were observed between PSMA- and PSA-based responses for both criteria (Φ = 0.79 and 0.66, respectively). After a median follow-up of 25 mo (interquartile range, 21-43 mo), the median overall survival was significantly longer for PSMA-R than PSMA-NR (54 vs. 22 mo) for both the EAU/EANM criteria and RECIP 1.0, with hazard ratios of 6.9 (95% CI, 1.9-26; P = 0.004) and 5.6 (95% CI, 1.69-18.26, P = 0.005), respectively. No significant difference in predictive accuracy was found between the 2 criteria (C-index, 0.79 vs. 0.76, respectively, P = 0.54). Flare phenomena at the second PSMA PET study were not observed in our cohort. Conclusion: Our results demonstrate that PSMA PET/CT is a valuable imaging biomarker for response assessment and overall survival prediction when performed at 3 mo after ARPI treatment initiation in mCRPC patients. Both proposed PSMA response criteria (EAU/EANM and RECIP 1.0) seem to perform equally well. No PSMA flare was observed. Prospective validation of these findings is strongly needed.