FDG-PET-Guided Radiation Therapy for Prostate Cancer

Recruiting at 4 trial locations

Overseen By Study Coordinator

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Northwestern University

Must be taking: Androgen deprivation therapy

Disqualifiers: Castration resistant prostate cancer, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

125 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial compares the effect of FDG-positron emission tomography (PET)-guided metastasis directed radiation therapy (MDRT) in combination with standard treatments to standard treatments alone in treating patients with prostate cancer that is sensitive to androgen-deprivation therapy (ADT) and has spread from where it first started (primary site) to other places in the body (metastatic). Prostate cancer is the second leading cause of cancer death among men in the United States, despite the approval of several life-prolonging treatments by the Food and Drug Administration. However, over the past 10 years, there have been significant improvements in prolonging the lives of those with metastatic hormone sensitive prostate cancer, specifically by adding treatments to standard therapy, such as ADT. More recently, trials have demonstrated a benefit of using radiotherapy (high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors) to delay the progression of cancer and prolong life for patients with metastatic disease. Imaging scans with FDG-PET may be able to identify cancer sites that remain active despite standard treatment. Giving MDRT plus standard treatment to patients with FDG-PET-identified cancer sites may work better than standard treatment alone in treating metastatic hormone sensitive prostate cancer.

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

The trial does not specify that you need to stop your current medications. In fact, it mentions that you will continue your standard treatment while participating in the study. However, any changes in your treatment due to side effects or other reasons should be discussed with the study team.

What data supports the effectiveness of the treatment FDG-PET-Guided Radiation Therapy for Prostate Cancer?

Research suggests that PET imaging, including FDG-PET, can help in identifying and targeting specific areas of prostate cancer, potentially improving the accuracy and effectiveness of radiation therapy. Although more studies are needed, PET imaging has shown promise in guiding individualized treatment and improving outcomes in prostate cancer management. ^{1 2 3 4 5}

How is FDG-PET-guided radiation therapy different from other prostate cancer treatments?

FDG-PET-guided radiation therapy for prostate cancer is unique because it uses a special imaging technique (FDG-PET) to detect and target metastatic disease, potentially improving the precision of radiation therapy. This approach is particularly useful for identifying and treating metastatic lesions that might not be visible with standard imaging methods. ^{1 6 7 8 9}

Research Team

David VanderWeele

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for men with prostate cancer that still responds to hormone therapy and has spread beyond the original site. Participants must be suitable for standard treatments, including antiandrogen therapy and chemotherapy. Specific details on inclusion or exclusion criteria are not provided.

Inclusion Criteria

Patients must have the ability to understand and the willingness to sign a written informed consent document prior to registration

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the endpoints for this study, in the opinion of the treating investigator, are eligible

Patients must have a life expectancy of at least 6 months, in the opinion of the treating investigator

Exclusion Criteria

I started advanced prostate cancer treatment more than 26 weeks ago.

My prostate cancer is growing despite low testosterone levels.

I started hormone therapy for cancer more than 26 weeks ago but less than 1 year ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo FDG-PET scan after 6 months of SOC cytotoxic chemotherapy + ADT, followed by MDRT for PET-avid disease

6 months

Multiple visits for scans and treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

36 months

Follow-up visits at 3 months, 6 months, and every 6 months thereafter

Treatment Details

Interventions

• FDG-PET-Guided Metastasis Directed Radiation Therapy

Trial Overview The study compares FDG-PET-guided radiation therapy combined with standard treatments against standard treatments alone in metastatic hormone sensitive prostate cancer. The goal is to see if adding targeted radiation improves outcomes.

Participant Groups

Group I: Arm 2A (FDG-PET, MDRT, SOC ADT) Experimental Treatment 5 Interventions

Patients undergo an FDG-PET scan after 6 months of SOC ADT. Patients with PET-avid disease continue their SOC ADT and undergo MDRT to up to 5 disease sites in the absence of unacceptable toxicity. Patients undergo an additional FDG-PET scan at 6 months. Patients also undergo CT and bone scans throughout the trial.

Group II: Arm 1A (FDG-PET, MDRT, SOC cytotoxic chemotherapy & ADT) Experimental Treatment 6 Interventions

Patients undergo an FDG-PET scan after 6 months of SOC cytotoxic chemotherapy + ADT. Patients with PET-avid disease continue their SOC ADT and undergo MDRT to up to 5 disease sites in the absence of unacceptable toxicity. Patients also undergo CT and bone scans throughout the trial.

Group III: Arm 1B (FDG-PET, SOC cytotoxic chemotherapy & ADT) Active Control 5 Interventions

Patients undergo an FDG-PET scan after 6 months of SOC cytotoxic chemotherapy + ADT. Patients with PET-avid disease continue their SOC ADT on study. Patients also undergo CT and bone scans throughout the trial.

Group IV: Arm 1C (FDG-PET, SOC cytotoxic chemotherapy & ADT) Active Control 5 Interventions

Patients undergo an FDG-PET scan after 6 months of SOC cytotoxic chemotherapy + ADT. Patients without PET-avid disease continue their SOC ADT on study. Patients also undergo CT and bone scans throughout the trial.

Group V: Arm 2B (FDG-PET, SOC ADT) Active Control 4 Interventions

Patients undergo an FDG-PET scan after 6 months of SOC ADT. Patients with PET-avid disease continue their SOC ADT on study and undergo an additional FDG-PET scan at 6 months. Patients also undergo CT and bone scans throughout the trial.

Group VI: Arm 2C (FDG-PET, SOC ADT) Active Control 4 Interventions

Patients undergo an FDG-PET scan after 6 months of SOC ADT. Patients without PET-avid disease continue their SOC ADT on study and undergo an additional FDG-PET scan at 6 months. Patients also undergo CT and bone scans throughout the trial.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 74 patients with nonmetastatic prostate cancer, those who received stereotactic body radiotherapy (SBRT) for up to five detected metastases showed significantly better metastasis-free survival (MFS) compared to those who continued androgen deprivation therapy (ADT) alone, with a median MFS of not reached versus 11.0 months for the ADT group.

The SBRT group achieved a PSA response greater than 90% in 86% of patients, and there were no severe adverse events (grade ≥3), indicating that this treatment is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiotherapy for Lesions Detected via 68Ga-Prostate-specific Membrane Antigen and 18F-Fluorodexyglucose Positron Emission Tomography/Computed Tomography in Patients with Nonmetastatic Prostate Cancer with Early Prostate-specific Antigen Progression on Androgen Deprivation Therapy: A Prospective Single-center Study. Pan, J., Wei, Y., Zhang, T., et al.[2022]

18F-FDG PET imaging, while traditionally thought to be less useful for prostate cancer, can actually help evaluate metastatic disease and assess therapy response in men with castration-resistant prostate cancer, based on limited evidence.

Emerging imaging techniques like 3'-deoxy-3'-18F-fluorothymidine may enhance the ability to localize aggressive prostate tumors and evaluate treatment responses, suggesting a potential for more targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET of Glucose Metabolism and Cellular Proliferation in Prostate Cancer. Jadvar, H.[2018]

In a study of 37 men with recurrent prostate cancer, PSMA-PET imaging was effective in identifying distinct disease phenotypes, which could help tailor treatment strategies despite conventional imaging showing no visible disease.

Patients with PSMA-avid disease not suitable for metastasis-directed therapy had a significantly shorter time to develop castrate-resistant prostate cancer, highlighting the importance of PSMA-PET in predicting disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligometastasis in Prostate Cancer: Can We Learn from Those "Excluded" from a Phase 2 Trial? Glicksman, RM., Murad, V., Santiago, AT., et al.[2023]

Radiotherapy as a metastasis-directed therapy (MDT) for oligometastatic prostate cancer shows promising results, with median progression-free survival ranging from 1 to 3 years based on data from over 1000 patients.

MDT appears to improve cancer-specific and overall survival compared to standard care for lymph node metastases, with adverse events mostly limited to mild grades (1-2), indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy as metastasis-directed therapy for oligometastatic prostate cancer. De Bleser, E., Tran, PT., Ost, P.[2022]

Positron emission tomography (PET) is increasingly being used in prostate cancer management, particularly in radiation therapy, to improve tumor detection and treatment accuracy through advanced imaging techniques and specific PET tracers.

Recent studies suggest that PET quantification methods can serve as predictive biomarkers, potentially guiding personalized treatment plans and enhancing patient outcomes, although further validation is needed for their application in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET guidance in prostate cancer radiotherapy: Quantitative imaging to predict response and guide treatment. Cattaneo, GM., Bettinardi, V., Mapelli, P., et al.[2017]

In a study of 25 patients with prostate cancer, FDG PET-CT showed limited effectiveness in identifying untreated primary tumors, with only a 33% sensitivity for detecting primary lesions.

However, FDG PET-CT was more effective in detecting metastatic disease, successfully identifying metastases in 12 out of 16 patients with a history of treatment and recent PSA relapse, suggesting its potential utility in specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic role of fluorodeoxyglucose positron emission tomography-computed tomography in prostate cancer. Liu, Y.[2021]

Radiation therapy (RT) is commonly used for treating early-stage prostate cancer and alleviating symptoms in metastatic cases, but its effectiveness in extending survival for metastatic disease is not well established.

The review highlights the potential of localized RT in oligometastatic disease and suggests future research into RT as an immune-sensitizing therapy, emphasizing the need for advanced imaging techniques to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy in Oligometastatic Prostate Cancer. Chinniah, S., Stish, B., Costello, BA., et al.[2022]

In a study of 84 prostate cancer patients, 74% of metastatic lesions were found suitable for biology-guided radiotherapy (BgRT) using a 10-mm tracking zone, indicating a high potential for effective treatment targeting.

However, some lesions were adjacent to non-tumor tissues with PSMA uptake, such as the bladder and ureter, which may complicate BgRT and necessitate careful consideration during treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2022]

In a study of 176 prostate cancer patients with oligometastases, 68Ga-PSMA PET/CT-based metastasis-directed treatment (MDT) resulted in a 2-year overall survival rate of 87.6% and a progression-free survival rate of 63.1%.

The treatment demonstrated a high local control rate of 93.2% at the irradiated site, with no patients experiencing severe acute toxicity, indicating that MDT is both effective and safe for managing oligometastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002). Hurmuz, P., Onal, C., Ozyigit, G., et al.[2020]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Stereotactic Radiotherapy for Lesions Detected via 68Ga-Prostate-specific Membrane Antigen and 18F-Fluorodexyglucose Positron Emission Tomography/Computed Tomography in Patients with Nonmetastatic Prostate Cancer with Early Prostate-specific Antigen Progression on Androgen Deprivation Therapy: A Prospective Single-center Study. [2022]

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

PET of Glucose Metabolism and Cellular Proliferation in Prostate Cancer. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Oligometastasis in Prostate Cancer: Can We Learn from Those "Excluded" from a Phase 2 Trial? [2023]

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

Radiotherapy as metastasis-directed therapy for oligometastatic prostate cancer. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

PET guidance in prostate cancer radiotherapy: Quantitative imaging to predict response and guide treatment. [2017]

6. Greece pubmed.ncbi.nlm.nih.gov

Diagnostic role of fluorodeoxyglucose positron emission tomography-computed tomography in prostate cancer. [2021]

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

Radiation Therapy in Oligometastatic Prostate Cancer. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer. [2022]

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

Treatment outcomes of metastasis-directed treatment using 68Ga-PSMA-PET/CT for oligometastatic or oligorecurrent prostate cancer: Turkish Society for Radiation Oncology group study (TROD 09-002). [2020]