Adaptive Radiotherapy + Hormone Therapy for Prostate Cancer

Overseen By Hiram A Gay, M.D.

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must be taking: Androgen deprivation

Must not be taking: Systemic chemotherapy

Disqualifiers: Metastatic disease, Prior prostatectomy, Uncontrolled illness, 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: 9

Duration: 5 weeks

30 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had systemic chemotherapy within 3 years prior to treatment start, and you must not have prior androgen deprivation therapy unless it started within 60 days before treatment. It's best to discuss your current medications with the trial team.

What data supports the idea that Adaptive Radiotherapy + Hormone Therapy for Prostate Cancer is an effective treatment?

The available research shows that adding stereotactic ablative radiotherapy (SABR) to standard treatment for prostate cancer can slow the disease's growth and improve survival rates. For instance, the ORIOLE trial found that SABR slowed disease progression in men with hormone-sensitive metastatic prostate cancer, allowing them to delay further hormone therapy. Additionally, the SABR-COMET trial reported a significant improvement in overall survival for patients treated with SABR. These findings suggest that combining adaptive radiotherapy with hormone therapy can be an effective treatment for prostate cancer. ^{1 2 3 4 5}

What safety data exists for adaptive radiotherapy and hormone therapy in prostate cancer treatment?

The safety data for adaptive radiotherapy, including stereotactic body radiation therapy (SBRT) and stereotactic ablative radiotherapy (SABR), combined with hormone therapy (ADT) for prostate cancer, indicates that these treatments are generally safe and effective. In a study of 400 patients treated with SABR, no severe late adverse effects were observed, and only a small percentage experienced acute reactions. Another study comparing SBRT to conventional therapy found SBRT to be a promising non-invasive alternative with potential benefits in quality of life and reduced toxicity. Long-term data from a 7-year study also supports the safety and effectiveness of SBRT, showing excellent disease control with manageable toxicity levels. ^{6 7 8 9 10}

Is Adaptive Stereotactic Body Radiation Therapy a promising treatment for prostate cancer?

Yes, Adaptive Stereotactic Body Radiation Therapy (SBRT) is a promising treatment for prostate cancer. It can improve survival, delay further cancer spread, and slow down cancer growth, allowing patients to postpone additional treatments. ^{1 2 3 4 11}

What is the purpose of this trial?

This trial is a prospective clinical trial designed to demonstrate the safety and feasibility of whole-pelvis adaptive prostate stereotactic body radiation therapy (SBRT) with a tumor boost to the magnetic resonance (MR)-detected sites of disease. The hypothesis is that this treatment approach will be safe and feasible with \<15% of patients experiencing an acute CTCAEv5 grade ≥3 genitourinary (GU) or gastrointestinal (GI) adverse event.

Research Team

Amit Bhatt, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Men over 18 with high-risk or unfavorable intermediate-risk prostate cancer, who haven't had prior treatments like chemotherapy or radical prostatectomy in the last 3 years. They should have an ECOG performance status ≤1, no evidence of metastatic disease, and be able to start hormone therapy within 60 days of radiation treatment.

Inclusion Criteria

Able to understand and willing to sign an IRB approved written informed consent document

Able to complete relevant patient-reported quality-of-life questionnaires

My condition is classified as unfavorable intermediate-risk with specific risk factors.

Exclusion Criteria

I have undergone major prostate cancer treatment.

My scans show cancer has spread to my lymph nodes or other parts of my body.

AUA urinary symptom score ≥ 20

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Adaptive stereotactic body radiotherapy (SBRT) with simultaneous integrated boosts to the prostate and MR-detected nodules

5 weeks

5 visits (in-person)

Androgen Deprivation Therapy (ADT)

ADT administered according to institutional standard, with a minimum of 4 months for intermediate-risk and 1 year for high-risk disease

4-24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of biochemical recurrence and overall survival

60 months

Every 3 months until month 24, then as needed

Treatment Details

Interventions

• Adaptive Stereotactic Body Radiation Therapy
• Androgen deprivation therapy

Trial Overview The trial is testing a new way to deliver radiation (Ethos Varian system) that adapts to the shape of the tumor daily, combined with hormone therapy. It aims to see if this method can target tumors more precisely while reducing side effects.

Participant Groups

Group I: Adaptive stereotactic body radiotherapy (SBRT) Experimental Treatment 3 Interventions

* Treatment consists of adaptive dose-escalated stereotactic body radiotherapy (SBRT) to the pelvic nodes to 25 Gy in 5 once or twice weekly fractions with simultaneous integrated boosts (SIB) to the prostate and proximal seminal vesicles to 36.25 Gy in 5 fractions (full seminal vesicles if involved), to the prostate to 40 Gy in 5 fractions, and to the involved MR-detected nodule(s) to up to 50 Gy in 5 fractions. * Androgen deprivation therapy (ADT) will be administered to study patients according to institutional standard. Unfavorable Intermediate-risk Disease: Patients should receive a minimum of 4 months of ADT. Patients can receive longer duration of ADT at the discretion of the treating physician. High-risk disease: Patients should receive a minimum of 1 year of ADT. Patients can receive up to 2 years of ADT at the discretion of the treating physician.

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

Approved in European Union as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer

Approved in United States as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer

Approved in Canada as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Findings from Research

In a study involving 20 prostate cancer patients treated with Adaptive Stereotactic Body Radiotherapy (SBRT), the delivered dose was confirmed to be adequate, ensuring that the target area received at least 95% of the prescribed dose while minimizing exposure to surrounding organs.

The study demonstrated that both the daily re-computed doses and cumulative doses were consistent, indicating that the online MRI guidance effectively maintained treatment accuracy despite potential prostate motion during the longer session times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time. Ruggieri, R., Rigo, M., Naccarato, S., et al.[2021]

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]

The phase II ORIOLE trial found that adding stereotactic ablative radiotherapy (SABR) to standard treatment significantly slowed disease progression over 6 months in men with hormone-sensitive metastatic prostate cancer, allowing for a delay in androgen deprivation therapy.

Further research is necessary to explore whether SABR, either alone or in combination with immunotherapies, can effectively prevent the development of new metastases in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intense Radiotherapy Slows Prostate Cancer Growth. [2021]

Stereotactic ablative body radiotherapy (SABR) has been shown to significantly improve overall survival in men with oligometastatic prostate cancer, especially following the results of the SABR-COMET trial.

Combining SABR with androgen deprivation therapy (ADT) may enhance treatment effectiveness by sensitizing prostate cancer cells to radiation, and this review explores strategies to counteract resistance linked to the androgen receptor pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen Receptor Gene Pathway Upregulation and Radiation Resistance in Oligometastatic Prostate Cancer. Saxby, H., Boussios, S., Mikropoulos, C.[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]

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 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]

This study investigates the use of stereotactic body radiotherapy (SBRT) as a non-invasive boost treatment for high-risk prostate cancer, comparing it to conventional fractionation external beam radiotherapy (CF-EBRT) in a randomized trial with 100 patients.

The primary goal is to assess the impact of SBRT on patient quality of life and treatment-related toxicity, particularly focusing on bowel and urinary function, over a period of up to 6 months after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Trial of Prostate Boost Irradiation With Stereotactic Body Radiotherapy (SBRT) or Conventional Fractionation (CF) External Beam Radiotherapy (EBRT) in Locally Advanced Prostate Cancer: The PBS Trial (NCT03380806). Isfahanian, N., Lukka, H., Dayes, I., et al.[2021]

In a study of 515 patients treated with stereotactic body radiation therapy (SBRT) for prostate cancer, the 7-year freedom from biochemical failure rates were excellent, with 95.8% for low-risk, 89.3% for intermediate-risk, and 68.5% for high-risk patients, indicating strong disease control.

The treatment was found to be safe, with no acute Grade 3 or 4 complications and low rates of late toxicity (4% for rectal and 9.1% for urinary Grade 2 toxicity), while quality of life measures returned to baseline within 2 years post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life and Toxicity after SBRT for Organ-Confined Prostate Cancer, a 7-Year Study. Katz, AJ., Kang, J.[2022]

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. Italy pubmed.ncbi.nlm.nih.gov

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time. [2021]

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

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

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

Intense Radiotherapy Slows Prostate Cancer Growth. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Androgen Receptor Gene Pathway Upregulation and Radiation Resistance in Oligometastatic Prostate Cancer. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

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

A Randomized Phase II Trial of Prostate Boost Irradiation With Stereotactic Body Radiotherapy (SBRT) or Conventional Fractionation (CF) External Beam Radiotherapy (EBRT) in Locally Advanced Prostate Cancer: The PBS Trial (NCT03380806). [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Quality of Life and Toxicity after SBRT for Organ-Confined Prostate Cancer, a 7-Year Study. [2022]

11. 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]