Stereotactic Ablative Radiotherapy for Prostate Cancer

Recruiting in Dallas (>99 mi)

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Androgen deprivation therapy

Must not be taking: 2nd generation anti-androgens

Disqualifiers: Invasive malignancy, AIDS, severe comorbidity, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Since high risk prostate cancer requires higher radiation, this study is being done to determine the maximum tolerated dose of radiation to the prostate and pelvic regions. Also to determine the feasibility and safety of each treatment fraction by using cone-beam Computed Tomography(CT) information and high speed Graphics Processing Unit based computation treatment planning systems. We also plan to determine the safety of treatment to the prostate. Health-related quality of life will be measured as part of current clinical practice. * Determine the maximum tolerated dose (MTD) or to safely escalate dose to the pelvic nodal using 90 day acute toxicity endpoint * Determine feasibility and safety of adaptive real time re-planning of the pelvic nodal region at each treatment fraction by using cone-beam CT (CBCT) information and high speed GPU based computation treatment planning systems * Determine the safety and tolerability of 9.5 Gy per fraction in five fractions (47.5 Gy total dose) to the prostate * Determine the feasibility and safety of temporal enhanced ultrasound for prostate lesion tracking during radiation therapy * To follow tumor related outcomes (i.e. PSA control, progression-free survival (PFS), distant metastasis (DM) free survival, and overall survival (OS) * Health-related quality of life (HRQOL) will be measured as part of current clinical practice Patients in each dose cohort will all be treated as a single group for dose escalation. There will be two levels of dose escalation-to prostate lesions and to pelvic lymph node region. Prostate/SV PTV will be treated at a fixed dose of 9.5 Gy per fraction for 5 fractions (47.5 Gy) based on our previous phase I/II study experiences. The starting dose for the dose escalation to the pelvic region PTV will be 4.5 Gy per fraction for 5 fractions (total dose= 22.5 Gy). Subsequent cohorts of patients will receive an additional 0.5 Gy per treatment (total 2.5 Gy per escalation). The starting dose for MRI-visible prostatic lesions will be 10 Gy and subsequent cohorts will receive an additional 0.5Gy per treatment (total of 2.5Gy per escalation).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot receive other cancer treatments like chemotherapy or certain hormone therapies while participating in this study.

What data supports the effectiveness of the treatment Stereotactic Ablative Radiotherapy (SABR) for prostate cancer?

Stereotactic Ablative Radiotherapy (SABR) is a promising treatment for localized prostate cancer, showing similar effectiveness to brachytherapy (a type of radiation treatment) with potentially fewer side effects. It is well-tolerated and may delay further treatment in cases of oligometastatic prostate cancer, although more research is needed to confirm its benefits. ^{1 2 3 4 5}

Is stereotactic ablative radiotherapy (SABR) generally safe for humans?

Stereotactic ablative radiotherapy (SABR) has been used for various cancers, including prostate cancer, and while it shows promise in controlling tumors, some serious complications have been reported. Strategies to reduce these risks are important to ensure safety. ^{3 6 7 8 9}

How is Stereotactic Ablative Radiotherapy (SABR) different from other prostate cancer treatments?

Stereotactic Ablative Radiotherapy (SABR) is unique because it delivers high doses of radiation in fewer sessions compared to traditional radiation therapy, which typically uses lower doses over more sessions. This approach may be more effective for certain prostate cancer cases and is being explored for its potential benefits in both localized and oligometastatic prostate cancer. ^{2 3 10 11 12}

Research Team

Raquibul Hannan, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

Men over 18 with high-risk prostate cancer (Gleason score ≥8, PSA ≥20 ng/ml, or advanced stage) who can undergo MRI and are eligible for a rectal spacer. They must agree to use contraception during treatment and be able to give informed consent. Excluded are those with prior pelvic cancer treatments, certain heart conditions, active infections, recent TURP surgery, planned antineoplastic therapies, metastases evidence after staging studies, severe co-morbidities like AIDS or significant psychiatric illness.

Inclusion Criteria

Signed study specific informed consent form

My PSA level is 20 ng/ml or higher, or I haven't started hormone therapy for prostate cancer yet.

My lymph nodes are not cancerous as confirmed by tests within the last 3 months.

Exclusion Criteria

I have not had pelvic radiotherapy, chemotherapy, or surgery for prostate cancer.

I have been cancer-free for at least 3 years, except for non-melanoma skin cancer.

Patients should not have a history of significant psychiatric illness

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Suppression Therapy (ADT)

Participants receive androgen suppression therapy prior to radiation

8-12 weeks

Radiation Therapy

Participants receive stereotactic ablative radiotherapy (SABR) to prostate and pelvic regions

5 fractions

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Stereotactic Ablative Radiotherapy (SABR)

Trial Overview The trial tests the highest safe radiation dose that can be given to the prostate and pelvis using Stereotactic Ablative Radiotherapy (SABR). It also assesses real-time planning safety with cone-beam CT scans and GPU systems for each treatment fraction. The study aims to determine if higher doses improve tumor control without compromising quality of life.

Participant Groups

Group I: Stereotactic Ablative Radiotherapy Experimental Treatment 1 Intervention

Stereotactic Ablative Radiotherapy (SABR)

Stereotactic Ablative Radiotherapy (SABR) is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as SABR/SBRT for:

• Low-risk prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Approved in United States as SABR/SBRT for:

• Low-risk prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer
• Recurrent prostate cancer

Approved in United Kingdom as SABR/SBRT for:

• Low-risk prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

Findings from Research

Stereotactic ablative radiotherapy (SABR) has been shown to be feasible and well tolerated for low- and intermediate-risk prostate cancer patients, with promising results from large randomized studies comparing it to conventional treatments.

While SABR shows potential benefits and cost-effectiveness, there is currently insufficient data to recommend its use for high-risk prostate cancer patients outside of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer. Loblaw, A.[2021]

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]

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 152 men with intermediate risk prostate cancer, weekly stereotactic ablative radiotherapy (SABR) resulted in better short-term bowel and urinary quality of life compared to every other day treatment, but there were no significant differences in late toxicity or long-term quality of life outcomes after 62 months.

Both treatment regimens showed similar rates of biochemical failure and overall survival, indicating that while weekly SABR may reduce acute side effects, it does not compromise long-term efficacy or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT). Alayed, Y., Quon, H., Ong, A., et al.[2021]

Stereotactic ablative body radiation (SABR) is a promising non-invasive treatment for localized prostate cancer, showing similar efficacy to brachytherapy in terms of disease control and lower side effects, making it a potentially safer option.

SABR is also more cost-effective and resource-efficient compared to traditional radiation techniques, but further well-powered studies are needed to confirm its benefits before it can be considered standard care, especially for patients with metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy in patients with prostate cancer. Loblaw, A., Liu, S., Cheung, P.[2023]

Stereotactic body radiation therapy (SBRT) for localized prostate cancer showed similar 5-year survival rates (90.8% for SBRT vs. 88.1% for IMRT) and comparable freedom from biochemical failure (FFBF) rates, indicating its efficacy is on par with intensity-modulated radiation therapy (IMRT).

Both treatment methods had low toxicity, with no severe (grade 3 or higher) side effects reported, suggesting that SBRT is a safe alternative that offers the benefits of shorter treatment duration and lower costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propensity score matched comparison of SBRT versus IMRT for the treatment of localized prostate cancer. Oliai, C., Bernetich, M., Brady, L., 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]

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 radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

Stereotactic body radiation therapy (SBRT) for localized prostate cancer showed a high two-year biochemical relapse-free survival rate of 99%, indicating its efficacy in controlling the disease.

The treatment was well tolerated, with low rates of gastrointestinal (1%) and genitourinary (31%) toxicities, and most patients who were sexually potent before treatment maintained their potency two years later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience. Chen, LN., Suy, S., Uhm, S., et al.[2022]

Stereotactic body radiotherapy (SBRT) for localized prostate cancer shows promising results, with studies indicating that ultra-hypofractionated schedules (like 42.7 Gy in 7 fractions) are non-inferior to standard treatments in terms of 5-year biochemical recurrence-free survival and have similar tolerability.

Current evidence suggests that two-fraction SBRT may be the shortest effective treatment schedule, but caution is advised against single-fraction SBRT due to concerns about inferior efficacy, highlighting the need for ongoing trials to determine optimal fractionation schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus? Ong, WL., Loblaw, A.[2023]

Stereotactic body radiotherapy (SBRT) shows a high local control rate of 98.1% in treating oligorecurrent prostate cancer limited to lymph nodes, based on a systematic review of 363 patients across nine studies with a median follow-up of 19.23 months.

The treatment demonstrated a low incidence of toxicity, with only 5.6% of patients experiencing grade ≥2 adverse effects, and no cases of grade 4 toxicity, suggesting that SBRT is a safe option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring All Avenues for Radiotherapy in Oligorecurrent Prostate Cancer Disease Limited to Lymph Nodes: A Systematic Review of the Role of Stereotactic Body Radiotherapy. Ponti, E., Lancia, A., Ost, P., et al.[2022]

References

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

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT). [2021]

5. China pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy in patients with prostate cancer. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Propensity score matched comparison of SBRT versus IMRT for the treatment of localized prostate cancer. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

The march toward single-fraction stereotactic body radiotherapy for localized prostate cancer-Quo Vadimus? [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Exploring All Avenues for Radiotherapy in Oligorecurrent Prostate Cancer Disease Limited to Lymph Nodes: A Systematic Review of the Role of Stereotactic Body Radiotherapy. [2022]