Stereotactic Radiotherapy + Hormone Therapy for Prostate Cancer

(EXCALIBUR Trial)

Overseen By Vince Basehart

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Distant metastases, Neuroendocrine carcinoma, Prior pelvic radiotherapy, Crohn's disease, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

102 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial investigates the effect of extremely hypofractionated intensity modulated stereotactic body radiotherapy in treating patients with prostate cancer that has rising prostate specific antigen (PSA) after radical prostatectomy. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects.

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 Stereotactic Radiotherapy + Hormone Therapy for Prostate Cancer?

Research shows that stereotactic ablative radiotherapy (SABR) using the CyberKnife system is effective and safe for treating intermediate- to very-high-risk prostate cancer, and it may improve survival and delay further metastases in patients with oligometastatic prostate cancer. ^{1 2 3 4 5}

Is Stereotactic Radiotherapy with Hormone Therapy safe for prostate cancer treatment?

Stereotactic Ablative Radiotherapy (SABR) using the CyberKnife system has been shown to be generally safe for treating prostate cancer, with very few severe side effects reported. Most patients experienced only mild to moderate side effects, and no severe long-term adverse effects were observed in the studies. ^{1 5 6 7 8}

How is the treatment Stereotactic Body Radiation Therapy (SBRT) with CyberKnife different from other prostate cancer treatments?

Stereotactic Body Radiation Therapy (SBRT) with CyberKnife is unique because it delivers highly precise radiation to prostate cancer using hundreds of non-coplanar beams, which allows for targeting the tumor while minimizing damage to surrounding healthy tissue. This precision makes it a promising option for treating various risk levels of prostate cancer, including low-risk and oligometastatic cases. ^{1 2 3 9 10}

Research Team

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

Men over 18 with prostate cancer that's come back after surgery, shown by rising PSA levels. They should have had certain adverse features at the time of surgery or found cancer in lymph nodes. No prior pelvic radiotherapy, no distant metastases, and no specific other cancers or conditions like Crohn's disease.

Inclusion Criteria

I can take care of myself but may not be able to do active work.

I had surgery to remove prostate cancer.

My cancer has an intermediate or high risk based on the Decipher test.

Exclusion Criteria

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

I have had radiation therapy to my pelvic area before.

My cancer has spread to distant parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo stereotactic body radiotherapy (SBRT) every other day or on consecutive days for up to 14 days. Hormonal therapy may be administered at the discretion of the treating physician.

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 3 months for the first year, and then every 6 months for up to 5 years.

5 years

Every 3 months for the first year, then every 6 months

Treatment Details

Interventions

• Hormone Therapy
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing a high-precision radiation therapy called Stereotactic Body Radiation Therapy (SBRT) combined with Hormone Therapy to see if it can treat prostate cancer more effectively with fewer treatments and less damage to healthy tissue.

Participant Groups

Group I: Treatment (SBRT, hormone therapy) Experimental Treatment 2 Interventions

Patients undergo SBRT every other day or on consecutive days for up to 14 days. Patients may receive hormonal therapy at the discretion of the treating physician.

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

Approved in United States as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Approved in European Union as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Approved in Canada as Stereotactic Body Radiation Therapy for:

• Non-small cell lung cancer (NSCLC)
• Melanoma
• Renal cell carcinoma (RCC)
• Prostate cancer
• Oligoprogressive cancers

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Findings from Research

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 of 87 men with oligometastatic prostate cancer treated with stereotactic ablative radiotherapy (SABR), the median disease-free survival (DMFS) was 21.8 months for hormone-sensitive patients, indicating a significant benefit from this treatment.

Combining SABR with short-term androgen-deprivation therapy improved both biochemical progression-free survival (bPFS) and DMFS in patients with oligorecurrent hormone-sensitive prostate cancer, suggesting a potential strategy for enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer. Mercier, C., Claessens, M., De Troyer, B., et al.[2022]

A single session of stereotactic ablative body radiotherapy (SABR) for oligometastatic prostate cancer was found to be feasible and safe, with only one significant adverse event (a vertebral fracture) reported among 33 patients over a 2-year follow-up period.

The treatment resulted in high local progression-free survival rates of 97% at 1 year and 93% at 2 years, with nearly half of the patients (48%) avoiding the need for androgen deprivation therapy at the 2-year mark, indicating effective disease control and maintained quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. Siva, S., Bressel, M., Murphy, DG., et al.[2022]

In a study comparing two different fractionation schedules of stereotactic ablative radiotherapy (SABR) for prostate cancer, the 2-fraction treatment (26 Gy/2) showed significantly better quality of life (QOL) outcomes in the bowel domain compared to the 5-fraction treatment (40 Gy/5), with a lower rate of clinically important changes in bowel function.

Both treatment groups had low five-year biochemical failure rates (3.3% for 2-fraction and 4.6% for 5-fraction), indicating that the 2-fraction SABR is not only effective but also well tolerated, warranting further randomized trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials. Alayed, Y., Quon, H., Cheung, P., et al.[2020]

In a study of 84 low-risk prostate cancer patients treated with Stereotactic Ablative Body Radiotherapy (SABR), long-term quality of life (QOL) outcomes were generally positive, with a median follow-up of 50.8 months, although some patients reported declines in urinary (17.9%), bowel (26.2%), and sexual (37.5%) QOL domains.

Dosimetric factors such as rectal D1cc and penile bulb V35 were identified as significant predictors of worse QOL, highlighting the importance of adhering to strict dosimetric constraints to minimize side effects from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. Elias, E., Helou, J., Zhang, L., et al.[2018]

Stereotactic ablative radiotherapy (SABR) is a safe and effective treatment for low and intermediate risk prostate cancer, with only a 2.25% failure rate observed in a study of 400 patients over a median follow-up of 15 months.

The treatment resulted in a significant decline in prostate-specific antigen (PSA) levels, with no severe late adverse effects reported, indicating that SABR could be considered for more advanced cases of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyberknife Radioablation of Prostate Cancer – Preliminary Results for 400 Patients Miszczyk, L., Namysł Kaletka, A., Napieralska, A., et al.[2020]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Stereotactic ablative radiation (SAbR) at a dose of 45 Gy in 5 fractions shows a promising safety profile for treating localized prostate cancer, with acute urinary and gastrointestinal toxicity rates of 20.4% and 7.3%, respectively, and low rates of late toxicity after 2 years.

The treatment demonstrated excellent efficacy, with a biochemical failure-free survival rate of 100% at 1 year and 98.7% at 2 years, indicating strong disease control outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. Chen, L., Gannavarapu, BS., Desai, NB., et al.[2022]

In a study of 26 men with low- to intermediate-risk prostate cancer treated with CyberKnife SBRT, there was a significant reduction in PSA levels, indicating an effective biochemical response to the therapy.

Despite a decrease in testosterone levels post-treatment, there was no increase in biochemical hypogonadism one year after therapy, suggesting that CyberKnife SBRT is well-tolerated and does not significantly impact hormonal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer. Oermann, EK., Suy, S., Hanscom, HN., et al.[2022]

In a study of 29 prostate cancer patients treated with stereotactic body radiotherapy (SBRT) using a Cyberknife, PSA levels showed a significant decrease over time, with a median nadir of 0.329 ng/mL achieved after 23 months.

The treatment demonstrated a favorable safety profile, with only 3% of patients experiencing Grade 2 urinary toxicities and no severe late rectal toxicities reported, indicating that SBRT is a feasible option for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for prostate cancer: a preliminary report. Lee, YH., Son, SH., Yoon, SC., et al.[2022]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. [2018]

6. Thailand pubmed.ncbi.nlm.nih.gov

Cyberknife Radioablation of Prostate Cancer – Preliminary Results for 400 Patients [2020]

7. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

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

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for prostate cancer: a preliminary report. [2022]