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

226 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the changes in long-term physician-scored genitourinary toxicity achieved in prostate cancer patients eligible for stereotactic radiation therapy when both patients and physicians have access to convincing but non-validated germline signature that can characterize patients as having a low or high risk of developing toxicity after radiation therapy. The information learned from this study may guide patients' and physicians' decisions on radiotherapy fractionation.

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 data supports the effectiveness of the treatment Germline DNA-Based Radiosensitivity Biomarker, Hypofractionated Radiation Therapy, Hypofractionated Radiotherapy, HFRT, Stereotactic Body Radiation Therapy, Stereotactic Ablative Radiotherapy (SABR), CyberKnife for prostate cancer?

Research shows that using CyberKnife for hypofractionated radiotherapy in prostate cancer patients can effectively reduce prostate-specific antigen (PSA) levels, indicating a positive response to treatment. Additionally, studies report that this approach is well-tolerated with manageable side effects, making it a promising option for prostate cancer treatment. ^{1 2 3 4 5}

Is hypofractionated radiotherapy, including CyberKnife, safe for humans?

Studies show that hypofractionated radiotherapy, including CyberKnife, is generally safe for treating prostate cancer, with most patients experiencing mild to moderate side effects like urinary and gastrointestinal issues, which usually return to normal within months. ^{2 4 5 6 7}

How is hypofractionated radiation therapy different from other treatments for prostate cancer?

Hypofractionated radiation therapy, including Stereotactic Body Radiation Therapy (SBRT) delivered by CyberKnife, is unique because it uses larger doses of radiation in fewer sessions, allowing for a shorter treatment period. This method is precise, as it can track and adjust for prostate movement in real-time, potentially reducing damage to surrounding healthy tissue and offering a well-tolerated option with promising early results in terms of effectiveness and side effects. ^{1 2 3 4 5}

Research Team

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

1. England 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. [2022]

2. United States 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. [2022]

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

Dosimetric and radiobiological comparison of Cyberknife and Tomotherapy in stereotactic body radiotherapy for localized prostate cancer. [2018]

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

Acute toxicity after cyberknife-delivered hypofractionated radiotherapy for treatment of prostate cancer. [2022]

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

Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. [2022]

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

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. [2017]

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

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response. [2022]