Predictive Biomarker Testing for Prostate Cancer

Overseen by John Floberg, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Wisconsin, Madison

Must be taking: Androgen deprivation

Disqualifiers: Metastatic disease, Prior pelvic radiation

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is for patients with high-risk prostate cancer. It uses a combination of radiation, internal radioactive seeds, and hormone therapy. The goal is to find new ways to predict how well these treatments will work using advanced imaging and genetic tests.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since participants are required to undergo specific cancer treatments, it's best to discuss your current medications with the trial team.

What data supports the effectiveness of this treatment for prostate cancer?

Research shows that combining external beam radiation therapy (EBRT) with a brachytherapy boost can reduce cancer recurrence in prostate cancer patients compared to using EBRT alone. However, the addition of androgen deprivation therapy (ADT) to this combination does not clearly improve overall survival, although it may help with biochemical control of the cancer. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The combination of brachytherapy (internal radiation therapy) and external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT) has been shown to increase toxicity in men with high-risk prostate cancer, although it improves biochemical control. This suggests that while effective, there may be safety concerns related to increased side effects. ^{2 5 6 7 8}

How is the treatment for prostate cancer using androgen deprivation therapy, external beam radiation therapy, and prostate brachytherapy boost unique?

This treatment combines hormone therapy (to lower male hormones that fuel cancer growth), external radiation (to target cancer cells from outside the body), and internal radiation (brachytherapy) to deliver a high dose directly to the prostate, which may improve cancer control but can increase side effects compared to using external radiation and hormone therapy alone. ^{5 9 10 11 12}

Research Team

John Floberg, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for adults over 18 with high-risk prostate cancer, as defined by specific criteria like a PSA >20 or tumor stage ≥T3a. They must be able to undergo brachytherapy, have no prior pelvic radiation, and not have any metastatic disease. Participants should also be in good physical condition (ECOG 0-1) and free from other cancers for at least 5 years.

Inclusion Criteria

I am fully active or can carry out light work.

I am 18 years old or older.

My prostate cancer is confirmed by a tissue examination.

Exclusion Criteria

I have had radiation therapy in the pelvic area before.

My scans show cancer has spread to other parts of my body.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Pre-treatment PET/MRI scans and genomic marker evaluation as part of standard of care

2-4 weeks

1 visit (in-person)

Treatment

Participants receive EBRT + BTX + ADT with mid-treatment PET/MRI scans for research

3 months

Multiple visits (in-person) for treatment and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging and genomic markers for PSA recurrence

5 years

Every 6 months

Treatment Details

Interventions

• Androgen deprivation therapy (Hormone Therapy)
• External beam radiation therapy (Radiation Therapy)
• Positron emission tomography (PET)/magnetic resonance imaging (MRI) (Diagnostic Test)
• Prostate brachytherapy boost (Radiation Therapy)

Trial Overview The study aims to identify imaging and genetic markers that predict how well patients respond to treatment. It involves external beam radiation therapy, a brachytherapy boost, androgen deprivation therapy (ADT), along with PET/MRI scans. Patients will participate for up to five years.

Participant Groups

Group I: EBRT + BTX + ADT, PET and MRI Experimental Treatment 4 Interventions

Standard of care EBRT + BTX + ADT, with mid-treatment PET and MRI (or PET and CT) scans for research.

Androgen deprivation therapy is already approved in Canada for the following indications:

Approved in Canada as Androgen deprivation therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Robert Drape

University of Wisconsin, Madison

Chief Executive Officer since 2007

Executive MBA from the University of Wisconsin – Madison, Bachelor's degree in Biology from Augustana College (IL)

Dr. Ciara Barclay-Buchanan

University of Wisconsin, Madison

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Findings from Research

In a study of 46,325 men with high-risk prostate cancer, androgen deprivation therapy (ADT) improved overall survival for those receiving external beam radiation therapy (EBRT) alone, but not for those receiving combined EBRT and brachytherapy.

The findings suggest that while ADT is beneficial with EBRT, it may not enhance survival in patients treated with both EBRT and brachytherapy, highlighting the need for further research to evaluate the risks and benefits of ADT in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy. Yang, DD., Muralidhar, V., Mahal, BA., et al.[2018]

In a study of 992 men with localized prostate cancer, those treated with brachytherapy (BT) experienced the least decline in sexual function (SF), while those receiving a combination of external beam radiotherapy (EBRT) and BT reported the greatest decline in SF.

Short-term androgen ablation (STAD) initially led to lower SF scores, but by one year, the differences in sexual function and sexual bother (SB) among treatment groups diminished, indicating that any impairment from STAD is likely temporary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal assessment of changes in sexual function and bother in patients treated with external beam radiotherapy or brachytherapy, with and without neoadjuvant androgen ablation: data from CaPSURE. Speight, JL., Elkin, EP., Pasta, DJ., et al.[2007]

In a study of 54,642 prostate cancer patients, low-dose-rate brachytherapy boost (LDR-BB) was associated with significantly higher gastrointestinal (GI) toxicity (32.3%) compared to high-dose-rate brachytherapy boost (HDR-BB) (16.7%) and external beam radiation therapy (EBRT) monotherapy (18.7%).

High-dose-rate brachytherapy boost (HDR-BB) resulted in lower incidences of skeletal-related events (2.4%) and prostate cancer-specific mortality (2.7%) compared to EBRT monotherapy (2.8% and 3.5%, respectively), indicating HDR-BB may offer better long-term outcomes in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of High-Dose-Rate and Low-Dose-Rate Brachytherapy Boost on Toxicity, Functional and Cancer Outcomes in Patients Receiving External Beam Radiation Therapy for Prostate Cancer: A National Population-Based Study. Parry, MG., Nossiter, J., Sujenthiran, A., et al.[2021]

In a study of 120 prostate cancer patients treated with external beam radiation therapy and a low-dose-rate brachytherapy boost, the addition of androgen deprivation therapy (ADT) did not significantly improve biochemical disease-free survival, distant metastasis-free survival, or overall survival.

Both palladium-103 and iodine-125 brachytherapy boosts showed similar effectiveness in terms of survival outcomes, indicating that either option can be used without a significant difference in patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer. Strom, TJ., Hutchinson, SZ., Shrinath, K., et al.[2022]

A survey of 42 North American genitourinary physicians revealed a significant divide in treatment recommendations for high-risk prostate cancer, with 45% supporting the addition of brachytherapy (BT) boost to external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT), while 55% preferred EBRT and ADT alone.

Experts in brachytherapy were much more likely to recommend the BT boost, indicating that physician expertise significantly influences treatment decisions, which may impact future clinical guidelines and studies in prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dramatically Polarized Opinion on the Role of Brachytherapy Boost in Management of High-risk Prostate Cancer: A Survey of North American Genitourinary Expert Radiation Oncologists. McClelland, S., Sandler, KA., Degnin, C., et al.[2019]

Patients with unfavorable intermediate- and high-risk prostate cancer who received extreme dose escalation with a combination of external beam radiotherapy (EBRT) and brachytherapy were significantly less likely to receive androgen deprivation therapy (ADT), with an odds ratio of 0.67, indicating a notable decrease in ADT utilization.

The study suggests a potential underutilization of ADT in higher-risk patients undergoing combined radiation treatments, highlighting the need for further prospective studies to clarify the role of ADT in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer. Mohiuddin, JJ., Narayan, V., Venigalla, S., et al.[2019]

In a study of 507 patients with unfavorable prostate cancer, the addition of 6 months or less of androgen suppression therapy (AST) to high-dose radiation treatment did not improve biochemical control or overall survival rates compared to radiation alone.

Despite the lack of survival benefit, the combination treatment resulted in additional side effects and costs, suggesting that AST may not be necessary for this patient group when high radiation doses are used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No apparent benefit at 5 years from a course of neoadjuvant/concurrent androgen deprivation for patients with prostate cancer treated with a high total radiation dose. Martinez, A., Galalae, R., Gonzalez, J., et al.[2017]

In a study of 532 intermediate-risk and high-risk prostate cancer patients treated with high-dose external beam radiation therapy (EBRT) and concurrent androgen deprivation therapy (ADT), a posttreatment PSA level greater than 0.1 ng/mL at 6 months was found to be a strong independent predictor of worse biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM).

The duration of ADT did not show any predictive value for clinical outcomes, suggesting that monitoring PSA levels at 6 months post-treatment could be crucial for identifying patients who may benefit from early salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis-Free Survival and Prostate Cancer-Specific Mortality. Naik, M., Reddy, CA., Stephans, KL., et al.[2017]

In a study of 375 patients with intermediate or high-risk prostate cancer treated with external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT), a nadir PSA level of 0.06 ng/ml was identified as a strong independent predictor of biochemical disease-free survival (BFS).

Other significant factors influencing biochemical recurrence included T-stage, Gleason score, and baseline PSA levels, highlighting the importance of tumor characteristics in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nadir PSA is a strong predictor of treatment outcome in intermediate and high risk localized prostate cancer patients treated by definitive external beam radiotherapy and androgen deprivation. Geara, FB., Bulbul, M., Khauli, RB., et al.[2018]

In a study of 307 prostate cancer patients with PSA levels > 20 ng/mL, those who received androgen deprivation therapy (ADT) for 12-24 months or more than 24 months showed significantly better biochemical control compared to those who received less than 6 months of ADT.

Longer durations of ADT (12-24 months and > 24 months) also resulted in improved cause-specific survival and overall survival, indicating that extended ADT is beneficial for patients undergoing external beam radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/ml? Berthelet, E., Pickles, T., Truong, PT., et al.[2007]

In a study of 1,045 patients with localized prostate cancer, those who achieved a pre-radiation therapy PSA nadir of ≤0.3 ng/mL after neoadjuvant androgen deprivation therapy (ADT) had significantly better 10-year survival outcomes, including a 74.3% PSA relapse-free survival rate compared to 57.7% for those with higher nadir values.

The findings suggest that achieving a lower PSA nadir is a strong predictor of long-term success in treatment, indicating that patients with higher nadir values may need additional therapies to improve their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical response to androgen deprivation therapy before external beam radiation therapy predicts long-term prostate cancer survival outcomes. Zelefsky, MJ., Gomez, DR., Polkinghorn, WR., et al.[2014]

References

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

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy. [2018]

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

Longitudinal assessment of changes in sexual function and bother in patients treated with external beam radiotherapy or brachytherapy, with and without neoadjuvant androgen ablation: data from CaPSURE. [2007]

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

Impact of High-Dose-Rate and Low-Dose-Rate Brachytherapy Boost on Toxicity, Functional and Cancer Outcomes in Patients Receiving External Beam Radiation Therapy for Prostate Cancer: A National Population-Based Study. [2021]

4. Brazil pubmed.ncbi.nlm.nih.gov

External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer. [2022]

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

Dramatically Polarized Opinion on the Role of Brachytherapy Boost in Management of High-risk Prostate Cancer: A Survey of North American Genitourinary Expert Radiation Oncologists. [2019]

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

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer. [2019]

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

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. [2020]

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

No apparent benefit at 5 years from a course of neoadjuvant/concurrent androgen deprivation for patients with prostate cancer treated with a high total radiation dose. [2017]

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

Posttreatment Prostate-Specific Antigen 6 Months After Radiation With Androgen Deprivation Therapy Predicts for Distant Metastasis-Free Survival and Prostate Cancer-Specific Mortality. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Nadir PSA is a strong predictor of treatment outcome in intermediate and high risk localized prostate cancer patients treated by definitive external beam radiotherapy and androgen deprivation. [2018]

11. Canada pubmed.ncbi.nlm.nih.gov

What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/ml? [2007]

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

Biochemical response to androgen deprivation therapy before external beam radiation therapy predicts long-term prostate cancer survival outcomes. [2014]