PSMA-Based PET Imaging for Prostate Cancer

Recruiting at 6 trial locations

Overseen By Michele L Reed, R.N.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, Hormone therapy

Disqualifiers: Metastatic disease, Prior prostate therapy, 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: 8

175 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: People with prostate cancer usually have their cancer imaged with a CT scan and bone scan. They then have their prostate gland removed. Researchers want to test a scan that might predict if prostate cancer will return after this surgery. Objective: To test if a PET/CT scan before the prostate gland is removed can predict if prostate cancer will return. Also, to test if this approach is better or worse than the usual approach for prostate cancer. Eligibility: Men ages 18 and older with prostate cancer that appears to be contained within the prostate but is at risk of having spread Design: Participants will be screened with: * Medical history * Blood tests * CT and MRI scans: Participants will lie in a machine. The machine will take pictures of the body. * Bone scan Participants will have a radiotracer injected into a vein. They will have a PET/CT scan of their whole body 60-90 minutes later. During the scan, they will lie on their back and stay still. Within 60 days after the scan, participants will have surgery. This will remove the prostate gland and lymph nodes around it. Some tissue will be used for genetic testing. If the PET/CT scan suggests the cancer has spread, participants may need to have another biopsy within 60 days after the scan. After surgery, participants will have follow-up visits for 5 years. They will have 5 visits the first year and 2 the second. Then they will have visits once a year. If participants cancer returns, they will have repeat PET/CT scans.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken any investigational agents in the past 28 days or have had hormone therapy for prostate cancer, except for limited use of androgen receptor antagonists.

What data supports the effectiveness of the treatment 18F-DCFPyL, PyL-PSMA-11, 18F-DCFPyL PET/CT for prostate cancer?

Research shows that 18F-DCFPyL PET/CT is better at finding prostate cancer that has spread compared to traditional imaging methods like CT scans. This new imaging technique helps doctors see cancer more clearly, which can improve how they manage and treat the disease. ^{1 2 3 4 5}

Is 18F-DCFPyL PET imaging safe for humans?

Initial studies on 18F-DCFPyL, a PSMA-targeted PET imaging agent, have shown it to be safe in humans, with evaluations focusing on its distribution in the body and radiation exposure levels. ^{1 4 6 7 8}

How is PSMA-based PET imaging different from other prostate cancer treatments?

PSMA-based PET imaging, specifically using the 18F-DCFPyL radiotracer, is unique because it targets the prostate-specific membrane antigen (PSMA) which is highly expressed in prostate cancer, allowing for more precise detection of cancerous lesions compared to conventional imaging methods like CT or bone scans. This imaging technique is particularly beneficial for identifying metastatic and recurrent prostate cancer, offering improved diagnostic performance and potentially impacting patient management. ^{1 2 6 9 10}

Research Team

Fatima H Karzai, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Men over 18 with high-risk prostate cancer that's likely still in the prostate but could have spread. They must be healthy enough for surgery, able to undergo certain scans and biopsies if needed, and not have had any prior treatments or other cancers within 3 years.

Inclusion Criteria

I am a man aged 18 or older.

I am planning to have surgery to remove my prostate and lymph nodes.

Ability of subject to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

I have had treatment for prostate cancer, including surgery, radiation, or chemotherapy.

Contraindication to MRI or PET: Patients weighing more than weight limit for the scanner tables or unable to fit within the imaging gantry, Prior reaction to 18F-DCFPyL, Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic device that are not MRI compatible at 3 T, Severe claustrophobia unresponsive to oral anxiolytics, Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, Other medical conditions deemed by the principal investigator (or associates) to make the subject unsafe/ineligible for the protocol procedures or for radical prostatectomy, A malignancy within the past 3 years for which prostatectomy is a contraindication, Radiotracer administered within 5 half-lives prior to the date of 18F-DCFPyL PET/CT imaging, PSMA-targeted imaging within 6 months with 18F-DCFPyL tracer prior to the date of 18F-DCFPyL PET/CT imaging. Participants can have PSMA targeted imaging with Gallium, Unable to refrain from fathering a child or donating sperm for 10 days after each 18FDCFPyL injection.

I have had hormone therapy for prostate cancer, but only short-term androgen blocker use.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Imaging and Pre-Surgery

Participants undergo 18F-DCFPyL PET/CT imaging and other baseline assessments before surgery

Up to 60 days

1 visit (in-person)

Surgery

Participants undergo radical prostatectomy and lymphadenectomy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for progression and response to treatment

5 years

5 visits in the first year, 2 visits in the second year, then annually

Treatment Details

Interventions

• 18F-DCFPyL

Trial Overview The trial is testing a new PET/CT scan using the tracer 18F-DCFPyL before removing the prostate gland to see if it can predict cancer recurrence better than current methods. Participants will be followed up for five years after surgery.

Participant Groups

Group I: 1/18F-DCFPyL PET/CT + radical prostatectomy Experimental Treatment 1 Intervention

18F-DCFPyL PET/CT with radical prostatectomy and lymphadenectomy

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Lantheus

Collaborator

Trials

1

Recruited

180+

Findings from Research

The novel PSMA-targeted PET radiotracer [(18)F]DCFPyL detected 139 sites of metastatic prostate cancer in patients, significantly outperforming conventional imaging modalities (CIM), which only identified 45 lesions.

This study suggests that [(18)F]DCFPyL PET imaging is more effective in identifying metastatic disease, especially in cases where CIM results were negative or equivocal, highlighting its potential as a superior diagnostic tool for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA-Based [(18)F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer. Rowe, SP., Macura, KJ., Mena, E., et al.[2022]

In a study of 93 patients with biochemically recurrent prostate cancer, 18F-DCFPyL PET/CT scans identified disease in 82% of cases, significantly outperforming conventional imaging, which had an accuracy below 20%.

The use of 18F-DCFPyL PET/CT led to a change in management for 44% of patients, often shifting treatment from androgen deprivation therapy to targeted radiotherapy, highlighting its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic performance of 18F-DCFPyL positron emission tomography/computed tomography for biochemically recurrent prostate cancer and change-of-management analysis. Chaussé, G., Ben-Ezra, N., Stoopler, M., et al.[2021]

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 study evaluated the dosimetry of the PET radiotracer 18F-DCFPyL in nine patients with metastatic prostate cancer, revealing that the lacrimal glands received the highest absorbed dose, which is important for understanding potential side effects during imaging and therapy.

Using advanced Monte-Carlo models, the research provided new insights into the dose received by the lacrimal and salivary glands, which are critical for assessing the safety and efficacy of 18F-DCFPyL in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA-targeted PET agent. Plyku, D., Mena, E., Rowe, SP., et al.[2018]

The study of [(18)F]DCFPyL in nine prostate cancer patients showed that it is safe, with no major adverse events related to the radiotracer observed during the imaging process.

[(18)F]DCFPyL demonstrated high accumulation in prostate cancer sites, indicating effective targeting for imaging, and its radiation dose is comparable to other PET radiotracers, making it a viable option for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Evaluation of [(18)F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer. Szabo, Z., Mena, E., Rowe, SP., et al.[2022]

The synthesized imaging agent [(18)F]DCFPyL effectively targets the prostate-specific membrane antigen (PSMA), showing a strong binding affinity (K(i) value of 1.1 nmol/L) and high uptake in PSMA-positive prostate tumors in mouse models.

[(18)F]DCFPyL demonstrated significant tumor delineation in PET imaging, with a remarkable uptake ratio of 358:1 between PSMA-positive and PSMA-negative tumors, indicating its potential as a specific imaging tool for prostate cancer with minimal uptake in non-target tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Chen, Y., Pullambhatla, M., Foss, CA., et al.[2021]

The automated synthesis of the radiotracer [(18)F]DCFPyL for PET imaging of prostate cancer was successful, yielding a good radiochemical yield of 23% in just 55 minutes, making it suitable for clinical applications.

[(18)F]DCFPyL demonstrated high uptake in PSMA-positive LNCaP tumors, with a two-step molecular trapping mechanism confirmed, indicating its potential effectiveness for targeted imaging in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated synthesis of [(18)F]DCFPyL via direct radiofluorination and validation in preclinical prostate cancer models. Bouvet, V., Wuest, M., Jans, HS., et al.[2020]

The study demonstrated that the 18F-DCFPyL PET imaging can effectively distinguish malignant prostate cancer from benign tissue, with significant differences in uptake values observed as early as 5 minutes post-injection in 10 patients with high-risk prostate cancer.

The pharmacokinetic analysis revealed that malignant prostate tissue had a 15-fold higher influx value (Ki) compared to benign prostatic hyperplasia and normal prostate tissue, indicating that 18F-DCFPyL PET imaging can be a valuable tool for early detection of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Dynamic 18F-DCFPyL PET/CT Imaging of Prostate Adenocarcinoma in High-Risk Primary Prostate Cancer Patients. Lu, M., Lindenberg, L., Mena, E., et al.[2023]

References

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

PSMA-Based [(18)F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer. [2022]

2. Canada pubmed.ncbi.nlm.nih.gov

Diagnostic performance of 18F-DCFPyL positron emission tomography/computed tomography for biochemically recurrent prostate cancer and change-of-management analysis. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of 18F-DCFPyL PSMA PET/CT for Prostate Cancer: A Meta-Analysis. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

The diagnostic performance of 18F-DCFPyL PET in patients with suspected prostate cancer: A systemic review and meta-analysis. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA-targeted PET agent. [2018]

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

Initial Evaluation of [(18)F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer. [2022]

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

2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Automated synthesis of [(18)F]DCFPyL via direct radiofluorination and validation in preclinical prostate cancer models. [2020]

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

A Pilot Study of Dynamic 18F-DCFPyL PET/CT Imaging of Prostate Adenocarcinoma in High-Risk Primary Prostate Cancer Patients. [2023]