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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new radiation method, Stereotactic Body Radiation Therapy, to treat prostate cancer in patients with rising PSA levels after surgery. The goal is to determine if fewer, higher doses of radiation can effectively target tumors while minimizing harm to healthy tissue. Participants may also receive hormone therapy (endocrine therapy) based on medical advice. This trial suits those who have undergone prostate cancer surgery and are experiencing rising PSA levels or have specific post-surgery features, such as positive surgical margins or cancer in lymph nodes. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that stereotactic body radiation therapy (SBRT) is generally safe and well-tolerated for treating prostate cancer. One study found that SBRT caused only minor side effects and was effective for low and intermediate-risk prostate cancer, meaning it did not cause major issues for most patients.

Hormone therapy, often used with SBRT, carries some risks. Some studies suggest it might increase the chance of heart problems, especially in older men. Discussing these risks with a doctor is important.

Overall, other studies have shown the treatments in this trial to be safe, but discussing any concerns with a healthcare provider is always wise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Stereotactic Body Radiation Therapy (SBRT) for prostate cancer because it offers a precise and targeted approach that can potentially reduce treatment time significantly compared to traditional radiation therapy. Unlike the standard of care, which often involves weeks of daily treatments, SBRT delivers high doses of radiation in just a few sessions over a period of up to 14 days. This method not only aims to improve patient convenience but also minimizes exposure to surrounding healthy tissue, potentially reducing side effects. Additionally, the combination with hormone therapy provides a tailored approach that can be adjusted based on the patient's specific needs, potentially enhancing treatment effectiveness.

What evidence suggests that stereotactic body radiation therapy and hormone therapy could be effective for prostate cancer?

Research shows that stereotactic body radiation therapy (SBRT) can effectively treat prostate cancer. Studies have found that SBRT offers excellent long-term control for low- and intermediate-risk prostate cancer. It matches the effectiveness of standard radiation therapy but requires less time. Additionally, hormone therapy significantly improves survival rates for prostate cancer patients. In this trial, participants will receive SBRT, and some may also receive hormone therapy at the treating physician's discretion, potentially enhancing disease management. ^{1 2 6 7 8}

Who Is on the Research Team?

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

I've had a bone scan or similar test within the last 4 months because my PSA level is over 1.0.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9007137/

Endocrine therapies for breast and prostate cancers Adjuvant tamoxifen therapy for 5 to 10 years is associated with a statistically significant absolute breast cancer mortality reduction at 15 years (mean [SD] ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4708248/

Role of hormonal therapy for prostate cancer Disease-specific and overall survival rates at 8 years in all patients were 89.1% and 75.0%, respectively. In addition, disease-specific survival rate at 8 ...

3. ahajournals.org ahajournals.org/doi/10.1161/HCG.0000000000000082

Impact of Hormonal Therapies for Treatment ... This consensus statement describes the risks associated with specific hormonal therapies used to treat breast and prostate cancer and provides an evidence- ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1558767325000473

Efficacy of Neoadjuvant Hormonal Therapy for High-Risk ... NHT with second-generation antiandrogens has shown significant improvements in oncological outcomes, including BCR and MFS, compared with RP alone (P < .001 for ...

5. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2775931

Efficacy of Endocrine Therapy for the Treatment of Breast ... In premenopausal women the addition of GnRHa leads to an improved disease-free survival, and in prostate cancer the use of a GnRHa improves ...

6. 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- ...

7. professional.heart.org professional.heart.org/en/science-news/Impact-of-Hormonal-Therapies-for-Treatment-of-Hormone-Dependent-Cancers-Breast-and-Prostate-on-the-C/commentary

Hormonal Based Therapies in the Treatment of Breast and ... Explore the potential cardiovascular impacts of hormonal therapies for the treatment of hormone-dependent breast & prostate cancer with ...

8. ecancer.org ecancer.org/en/news/22066-hormone-therapy-for-prostate-cancer-increases-the-risk-of-dying-from-cardiovascular-disease

Hormone therapy for prostate cancer increases the risk of ... Hormone therapy for prostate cancer increases the risk of cardiovascular disease-related death especially in older men, according to a population study.