Predictive Biomarker Testing for Prostate Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Wisconsin, Madison

Must be taking: Androgen deprivation

Disqualifiers: Metastatic disease, Prior pelvic radiation

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 3 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover new methods for predicting prostate cancer's response to treatment. Researchers use imaging scans and genetic tests to identify markers that may predict treatment success. The trial includes standard treatments such as hormone therapy (to lower male hormones), radiation therapy (using high-energy rays to kill cancer cells), and brachytherapy, a type of internal radiation. Men with high-risk prostate cancer planning to undergo these treatments are suitable candidates for this study. As an Early Phase 1 trial, this research seeks to understand how these predictive methods function in people, offering participants an opportunity to contribute to groundbreaking advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that treatments used in prostate cancer care, like those in this trial, are generally safe, though they can have side effects.

Studies have found that androgen deprivation therapy (ADT) works well but can cause side effects such as tiredness and hot flashes. Despite these effects, ADT is widely used and helps lower prostate-specific antigen (PSA) levels in many patients.

External beam radiation therapy (EBRT) is also well-tolerated. Some patients report side effects like skin irritation and fatigue, but these are usually manageable.

Brachytherapy, a type of internal radiation often used with EBRT, has improved cancer control. This treatment is considered safe, with possible side effects including urinary issues and discomfort, which typically decrease over time.

These treatments are standard for prostate cancer and are part of ongoing research to improve results and better manage side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how predictive biomarker testing can enhance prostate cancer treatments. Unlike standard treatments that follow a one-size-fits-all approach, this method uses mid-treatment PET and MRI scans to tailor therapies like androgen deprivation therapy, external beam radiation, and prostate brachytherapy boosts. This personalized approach aims to improve treatment effectiveness by adapting to how the cancer responds in real-time, potentially leading to better outcomes and fewer side effects.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that hormone therapy, known as androgen deprivation therapy (ADT), can significantly improve outcomes for prostate cancer patients. In a study of 3,710 patients, adding ADT prevented the cancer from spreading and slowed its progression.

Studies have also found that external beam radiation therapy (EBRT) is effective, with 74.4% of patients surviving for at least five years and 89.1% surviving specifically from prostate cancer. In this trial, participants will receive a combination of EBRT, brachytherapy boost, and ADT. Combining EBRT with brachytherapy, a type of internal radiation, has improved survival rates and reduced the risk of cancer spreading.

Using a brachytherapy boost along with EBRT has proven very effective in controlling prostate cancer, offering high rates of disease control and survival benefits. Together, these treatments provide a comprehensive approach to treating high-risk prostate cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

John Floberg, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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.

My prostate cancer is confirmed by a tissue examination.

My cancer is considered high-risk with a PSA over 20, or it's advanced.

Exclusion Criteria

I have had radiation therapy in the pelvic area before.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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 European Union, United States, Canada for the following indications:

Approved in European Union as Androgen deprivation therapy for:

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

Approved in United States as Androgen deprivation therapy for:

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

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+

Published Research Related to This Trial

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 585 high-risk prostate cancer patients treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT), a biopsy Gleason score (bGS) of 8 to 10 was identified as the strongest predictor of biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM).

The study found that the duration of ADT did not significantly impact patient outcomes, highlighting the importance of tumor characteristics over treatment length in predicting survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Tendulkar, RD., Reddy, CA., Stephans, KL., et al.[2020]

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 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]

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 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 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 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]

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 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 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]

Citations

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Effects of Androgen Deprivation Therapy on Prostate Cancer ... We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2588931125001312

Influence of Concomitant Androgen Deprivation Therapy ... Data from 3710 prostate cancer patients were analyzed. Addition of ADT to sRT improved MFS and PFS significantly, regardless of the duration ...

3. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Treatment advances including ADT have led to improvements in PCa management and survival, with trials reporting median survival of over 6 years ...

4. frontierspartnerships.org frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2024.12473/full

Clinical efficacy of different androgen deprivation therapies for ... This study evaluated the clinical efficacy of different androgen deprivation therapies in the treatment of PCa from the perspective of DCE-MRI

5. openurologyandnephrologyjournal.com openurologyandnephrologyjournal.com/VOLUME/17/ELOCATOR/e1874303X237036/FULLTEXT/

6-month Formulations of Androgen Deprivation Therapy for ... A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method:.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4094624/

Androgen deprivation therapy for prostate cancer: long-term ... ADT can normalize serum prostate specific antigen in over 90% of patients and results in sizable tumor response in 80% to 90%. This treatment can be done either ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38164028/

Comparison of Short-Term Outcomes and Safety Profiles ... This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel

8. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124000282

A 3-year Interim Analysis of the Observational J-ROCK Study In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone- ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0302283825004361

Short-term Androgen Deprivation Therapy and High-dose ... Among the 370 patients in the modified intention-to-treat population, 241 (65%) had intermediate-risk and 107 (28%) high-risk prostate cancer.