Biomarker Analysis for Prostate Cancer Radiotherapy Toxicity Prediction

(GARUDA Trial)

Overseen By Vince Basehart

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Neuroendocrine carcinoma, Small cell carcinoma, Distant metastases, Prior pelvic radiotherapy, Crohn's disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help prostate cancer patients and their doctors predict the risk of side effects from radiation therapy. Researchers analyze specific genetic markers using cheek swabs and blood samples to determine if a patient is more likely to develop genitourinary toxicity (urinary or genital side effects) from stereotactic body radiation therapy. Patients predicted to be at low risk can continue with the standard quick treatment, while those at higher risk might choose longer, less intense radiation options. Men diagnosed with prostate cancer, with no signs of the disease beyond the prostate and surrounding areas, might be a good fit for this trial. As an unphased trial, this study offers a unique opportunity for patients to contribute to personalized treatment strategies and improve future care.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this biomarker analysis is safe for prostate cancer patients?

Research has shown that hypofractionated radiation therapy, which uses higher doses over fewer sessions, is generally safe for prostate cancer patients. A large study involving 9,074 men across 13 trials found that this treatment is as effective as the traditional method and has similar side effects. Another review found no serious negative reactions in patients.

Stereotactic body radiation therapy (SBRT), which uses precise and strong radiation doses, also shows promising safety. Past patients have demonstrated that SBRT is well-tolerated, with manageable side effects.

Both treatments have undergone thorough study, indicating they are generally safe. However, individual experiences can vary, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to personalize prostate cancer treatment using biomarker analysis. Unlike standard radiotherapy, which is often standardized, this approach uses genomic DNA from cheek swabs and blood samples to predict each patient's risk of experiencing toxicity from Stereotactic Body Radiation Therapy (SBRT). This allows doctors to tailor the treatment plan, potentially improving safety and effectiveness. By identifying patients who are low-risk, they can confidently proceed with SBRT over a short period, while high-risk patients can be guided towards alternative radiotherapy options that might suit them better. This personalized approach could revolutionize how radiotherapy is administered, making it safer and more effective for individuals.

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

Research has shown that hypofractionated radiation therapy (HFRT) is effective for treating prostate cancer. A review of several studies found that HFRT prevents cancer recurrence more effectively than traditional methods. In a large study involving 9,074 men, researchers found no significant difference in survival rates after five years between HFRT and the usual treatment, supporting its effectiveness. Another study confirmed HFRT's safety and effectiveness, but higher daily doses did not improve cancer control and increased the risk of side effects. Overall, HFRT is a proven and effective option for treating prostate cancer. In this trial, participants will undergo genomic DNA testing to predict their risk of toxicity with different radiotherapy options, including HFRT and stereotactic body radiation therapy (SBRT). ^{1 2 3 4 6}

Who Is on the Research Team?

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Men with localized prostate adenocarcinoma, who have not had prior treatments like pelvic radiotherapy or prostate surgery, and do not have metastatic disease. They must be able to sign consent and follow the National Comprehensive Cancer Network guidelines for staging workups based on their risk group.

Inclusion Criteria

Staging workup as recommended by the National Comprehensive Cancer Network (NCCN) based on risk grouping

Ability to understand, and willingness to sign, the written informed consent

My prostate cancer is confirmed and hasn't spread beyond the prostate or seminal vesicles.

Exclusion Criteria

I have had cryosurgery, HIFU, or brachytherapy on my prostate.

I have a history of Crohn's disease, ulcerative colitis, or ataxia telangiectasia.

My prostate cancer is of the neuroendocrine or small cell type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy Planning and Biomarker Analysis

Patients undergo collection of cheek swab and blood samples for germline biomarker analysis and engage in discussions about radiotherapy options.

1-2 weeks

Radiotherapy Treatment

Patients receive radiotherapy based on biomarker results: SBRT over 14 days, conventionally fractionated radiotherapy over 63-70 days, or moderately hypofractionated radiotherapy over 28-35 days.

2-10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 1, 3, 6, 9, 12, 18, and 24 months, and then every 6 months for 4 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Germline DNA-Based Radiosensitivity Biomarker
• Hypofractionated Radiation Therapy
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing if knowledge of a patient's genetic predisposition to radiation toxicity (low or high risk) influences long-term genitourinary side effects after stereotactic radiation therapy for prostate cancer.

How Is the Trial Designed?

Group I: Treatment (radiotherapy, genomic DNA testing) Experimental Treatment 6 Interventions

Patients undergo SBRT per standard of care, then undergo collection of cheek swab and blood samples for the analysis of germline biomarkers. Afterwards, patients and their physicians engage in discussion about which form of radiotherapy to proceed with. Based on the decision, patients predicted to be at low risk of toxicity with SBRT continue to receive SBRT over 14 days while patients predicted to be at high risk of toxicity with SBRT will be counseled to undergo either conventionally fractionated radiotherapy over 63-70 days, moderate hypofractionated radiotherapy over 28-35 days, or may opt to still receive SBRT over 14 days per standard of care.

Hypofractionated Radiation Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in European Union as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Approved in Canada as Hypofractionated Radiotherapy for:

• Soft tissue sarcoma
• Extremity soft tissue sarcoma

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

MiraDX

Collaborator

Trials

1

Recruited

230+

Published Research Related to This Trial

In a study of 12 localized prostate cancer cases, Tomotherapy (HT) demonstrated superior dosimetric results compared to Cyberknife (CK), achieving better dose homogeneity, target coverage, and conformity, which are crucial for effective treatment.

HT also predicted lower late rectal toxicity and resulted in a significantly lower integral dose to the body, suggesting that it may offer clinical benefits by reducing the risk of side effects associated with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric and radiobiological comparison of Cyberknife and Tomotherapy in stereotactic body radiotherapy for localized prostate cancer. Chen, CY., Lee, LM., Yu, HW., et al.[2018]

In a study involving 24 patients with intermediate- to high-risk prostate cancer, hypofractionated stereotactic body radiation therapy (SBRT) using the CyberKnife system showed promising results, with a significant decrease in median PSA levels from 10.6 ng/ml to 1.5 ng/ml within 6 months post-treatment.

The treatment was well tolerated, with only mild acute urinary and gastrointestinal toxicities reported, and no severe Grade 3 or greater toxicities, indicating a favorable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of intensity modulated radiation therapy with hypofractionated stereotactic body radiation therapy (SBRT) boost in the treatment of intermediate- to high-risk prostate cancer. Oermann, EK., Slack, RS., Hanscom, HN., et al.[2022]

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

In a study involving 874 men with localized prostate cancer, stereotactic body radiotherapy (SBRT) was found to have similar rates of acute gastrointestinal and genitourinary toxicity compared to conventionally fractionated or moderately hypofractionated radiotherapy, suggesting that shorter treatment courses do not increase immediate side effects.

The study showed that only 12% of patients receiving conventional treatment experienced severe gastrointestinal toxicity, compared to 10% in the SBRT group, and 27% versus 23% for genitourinary toxicity, indicating that SBRT is a safe alternative without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Brand, DH., Tree, AC., Ostler, P., et al.[2022]

A systematic review of studies on stereotactic body radiation therapy (SBRT) for prostate cancer found that most patients experienced mild to moderate side effects, with severe toxicity occurring in less than 3% of cases, indicating that SBRT is generally well tolerated.

The review identified important dosimetric factors that influence toxicity, such as recommended dose constraints for the bladder, urethra, and rectum, which can help optimize treatment safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response. Wang, K., Mavroidis, P., Royce, TJ., et al.[2022]

In a study of 67 patients with low-risk prostate cancer treated with stereotactic body radiotherapy (SBRT), significant late bladder and rectal toxicities were infrequent, with no grade 4 toxicities reported and only 3% experiencing grade 3 bladder toxicity.

The 4-year PSA relapse-free survival rate was 94%, indicating that SBRT is effective in controlling prostate cancer and should be considered as a treatment option alongside other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. King, CR., Brooks, JD., Gill, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12548115/

evidence from 9074 men in 13 randomized clinical trials There was no statistically significant difference in relapse-free survival after five years of treatment between the HFRT and CFRT groups. In ...

2. uclahealth.org uclahealth.org/news/release/study-confirms-safety-and-efficacy-higher-dose-per-day

Study confirms safety and efficacy of higher-dose-per-day ... While dose-escalated MHFRT was expected to improve outcomes, the data showed no additional benefit in cancer control and a higher risk of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1879850023001753

Long-Term Outcomes of a Prospective Study on Highly ... In this study, the efficacy and safety of highly hypofractionated IMRT in 15 fractions were evaluated for low- to intermediate-risk prostate cancer. The 5- and ...

4. redjournal.org redjournal.org/article/S0360-3016(24)02047-9/fulltext

A Meta-Analysis of Randomized Trials HFRT demonstrates a statistically significant improvement in BCPFS for patients with localized prostate cancer when compared to CFRT.

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00034-8/abstract

Hypofractionated radiotherapy for prostate cancer (HYDRA) Hypofractionated radiotherapy for prostate cancer (HYDRA): an individual patient data meta-analysis of randomised trials in the MARCAP consortium.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12077468/

Hypofractionated radiotherapy for localized prostate cancer This trial aims to investigate the safety outcomes of HFRT in 15 fractions for treating patients with localized PCa.