Radiation Therapy for Prostate Cancer

(ASCENDE-SBRT Trial)

Recruiting at 12 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Canadian Cancer Trials Group

Must be taking: ADT, 5-alpha reductase

Must not be taking: Anticoagulants

Disqualifiers: Prior pelvic radiotherapy, Hip prosthesis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

710 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to answer the following question: Is the strategy to give higher doses of radiotherapy treatment over a shorter period of time using special equipment and fewer treatments (also known as Stereotactic Body Radiation Therapy or SBRT) as effective as usual external radiation therapy given with a brachytherapy boost (which involves radiation sources inserted directly into the prostate)?

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like anticoagulants may need to be stopped if they are unsafe for procedures involved in the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of this treatment for prostate cancer?

Research shows that radiation therapy, including methods like brachytherapy and internal radiation, can improve local control of prostate cancer and potentially enhance survival rates, especially in patients with low metastatic burden. Additionally, salvage radiotherapy has been found to improve survival in patients experiencing a recurrence of prostate cancer after surgery. ^{1 2 3 4 5}

Is radiation therapy for prostate cancer generally safe for humans?

Radiation therapy for prostate cancer is generally considered safe with an acceptable rate of side effects, especially with advanced techniques like 3D-conformal or intensity-modulated radiation therapy that minimize exposure to normal tissues. However, some patients may experience genitourinary, gastrointestinal, and sexual side effects, and those with certain genetic conditions may have increased sensitivity to radiation. ^{6 7 8 9 10}

How is radiation therapy unique for treating prostate cancer?

Radiation therapy for prostate cancer is unique because it uses high-energy rays to target and kill cancer cells, and recent advances in technology have improved its precision and effectiveness. Unlike some other treatments, it can be used alone or in combination with other therapies, and it is effective for both early-stage and advanced prostate cancer. ^{9 11 12 13 14}

Research Team

Andrew Loblaw

Principal Investigator

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

Eligibility Criteria

Men with prostate cancer diagnosed in the last 9 months can join this trial. They must have intermediate or high-risk factors like a Gleason score of 7-10, PSA levels of 10-20 ng/ml or higher, and certain stages of tumor growth (cT2b to cT4). Men who don't meet these specific cancer characteristics cannot participate.

Inclusion Criteria

I am taking medication for prostate enlargement or hair loss.

My prostate cancer is classified as high-risk.

Participants consent must be appropriately obtained

Exclusion Criteria

My prostate is larger than 60cc before starting hormone therapy.

Hip prosthesis

I am on blood thinners or have a bleeding disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Stereotactic Body Radiation Therapy (SBRT) or External Beam Radiation Therapy (EBRT) with a brachytherapy boost, combined with androgen deprivation therapy (ADT)

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8.6 years

Treatment Details

Interventions

• Brachytherapy
• Radiation

Trial Overview The study is comparing two types of radiation therapy for prostate cancer. One group will receive SBRT, which is a high-dose radiation treatment given over fewer sessions. The other group gets usual external radiation plus brachytherapy, where radioactive material is placed inside the prostate.

Participant Groups

Group I: SBRT Experimental Treatment 1 Intervention

Group II: EBRT + Brachy Boost Active Control 2 Interventions

Radiation is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

Radiotherapy (RT) significantly improves overall survival in men with newly diagnosed prostate cancer who have a low metastatic burden, with a hazard ratio of 0.64, indicating a 36% reduction in the risk of death compared to standard care alone.

In contrast, RT does not show a survival benefit for patients with high metastatic burden, and there were no significant differences in quality of life or severe toxicity between the treatment groups, suggesting RT is safe and effective for low-burden cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial. Parker, CC., James, ND., Brawley, CD., et al.[2023]

In a study of 647 patients with localized prostate carcinoma treated with radiation from 1975-1989, 61% achieved clinical disease-free status, highlighting the efficacy of local tumor control in improving patient outcomes.

The research found that reducing distant metastasis (26% survival advantage) was more beneficial for overall survival than improving local tumor control (14% survival advantage), especially in patients with poorly differentiated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential benefit of improved local tumor control in patients with prostate carcinoma. Kuban, DA., el-Mahdi, AM., Schellhammer, PF.[2019]

In a study of 159 men with locally advanced prostate cancer treated with radiotherapy, the 5-year freedom from biochemical failure was 76%, indicating that radiotherapy is effective in managing this condition.

Using 3-dimensional conformal radiotherapy (3DCRT) with higher doses significantly improved disease-free survival (DFS) to 78% compared to 51.5% for other techniques, highlighting the importance of treatment technique and dose in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From two-dimensional to three-dimensional conformal radiotherapy in prostate cancer: an Indian experience. Engineer, R., Bhutani, R., Mahantshetty, U., et al.[2010]

Radiation therapy is an effective treatment for localized prostate cancer, but there is still a significant rate of cancer persistence after treatment, indicating a need for improved methods.

New radiation techniques are being developed to enhance local control of the cancer while also aiming to preserve bladder and sexual function, and ongoing research seeks to identify which patients will benefit most from radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of radiotherapy in locally limited prostate cancer]. Herr, HW.[2006]

In a study of 151 prostate cancer patients who underwent salvage radiotherapy (sRT) after radical prostatectomy, PSA monitoring during treatment did not predict therapeutic success, indicating that PSA levels alone may not be reliable indicators of treatment effectiveness.

Despite the lack of predictive value from PSA kinetics, patients generally experienced a significant prolongation in PSA doubling times after sRT, suggesting that sRT provides a therapeutic benefit for most patients, even those with higher risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage radiotherapy in prostate cancer patients with biochemical relapse after radical prostatectomy : Prolongation of prostate-specific antigen doubling time in patients with subsequent biochemical progression. Lohm, G., Neumann, K., Budach, V., et al.[2018]

Image-guided radiation therapies, like 3D-conformal and intensity-modulated radiation therapy, allow for the safe delivery of high doses of radiation to prostate cancer patients with manageable side effects.

Escalating radiation doses has been shown to improve biochemical disease-free survival in certain patients, while interstitial brachytherapy is effective for those with favorable cancer characteristics, highlighting the need for long-term follow-up to evaluate treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiation therapy for prostate cancer]. Sumi, M.[2011]

In a study of 9,876 men who underwent radical prostatectomy, those who received postprostatectomy radiation therapy experienced significantly higher rates of gastrointestinal (1.81 times more likely) and urinary nonincontinence adverse events (1.83 times more likely) compared to those who did not receive radiation therapy.

The timing of radiation therapy after prostatectomy did not affect the risk of these adverse events, challenging the belief that delaying radiation therapy reduces the likelihood of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing adverse events of postprostatectomy radiation therapy for prostate cancer: evaluation of outcomes in the Regione Emilia-Romagna, Italy. Showalter, TN., Hegarty, SE., Rabinowitz, C., et al.[2015]

A patient with prostate cancer experienced severe side effects and ultimately died 25 months after salvage radiotherapy, highlighting the potential risks for individuals with impaired DNA repair mechanisms.

The case emphasizes the need for identifying patients with increased radiosensitivity, suggesting that screening for this trait could improve radiation protection and patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity : Case report and literature review. Fahrig, A., Koch, T., Lenhart, M., et al.[2018]

Recent advancements in radiation therapy for prostate cancer, such as intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT), have improved treatment precision, leading to reduced side effects and the ability to safely increase radiation doses.

Low dose rate (LDR) and high dose rate (HDR) brachytherapy are effective treatment options for localized prostate cancer, each with unique side effect profiles, while the potential benefits of proton therapy and stereotactic radiotherapy require further research through prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Localized prostate cancer: Radiotherapeutic concepts]. Grimm, M., Wenz, F.[2018]

Patients undergoing radiation therapy for prostate cancer commonly experience symptoms such as pain, lack of energy, drowsiness, and difficulty sleeping, which generally decrease over time during treatment.

Urination problems and diarrhea show more complex patterns, indicating that these symptoms can worsen or fluctuate, highlighting the need for tailored patient support throughout the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trajectories and predictors of symptom occurrence, severity, and distress in prostate cancer patients undergoing radiation therapy. Knapp, K., Cooper, B., Koetters, T., et al.[2022]

Recent advancements in radiation therapy technologies, such as intensity-modulated radiation therapy and proton therapy, have allowed for higher doses of radiation to be delivered to prostate cancer while reducing damage to surrounding healthy tissues.

Randomized trials indicate that while higher radiation doses improve clinical outcomes, they also increase toxicity, highlighting the need for ongoing research to fully assess the benefits and risks of these new treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging technologies in prostate cancer radiation therapy: improving the therapeutic window. Biagioli, MC., Hoffe, SE.[2017]

Radiation therapy for prostate cancer is undergoing significant advancements due to new technologies and ongoing clinical trials, which are improving treatment options.

The article reviews key findings from five studies that highlight the current effectiveness and future directions of radiation treatment for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy for prostate cancer: An evolving treatment modality. Chen, RC.[2020]

Recent advancements in radiation therapy for prostate cancer, including dose escalation and adjuvant radiation therapy, have shown to improve overall survival, particularly in patients with pT3 disease or positive margins after surgery.

Emerging techniques like hypofractionation, stereotactic body radiation therapy, and advanced technologies such as Calypso 4D tumor tracking are promising for enhancing treatment accuracy and reducing side effects, but they require further validation in large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on radiation-based therapies for prostate cancer. Kwok, Y., Yovino, S.[2010]

Radiation therapy, including brachytherapy and external beam radiotherapy, is an effective treatment option for newly diagnosed prostate cancer, as well as for salvage treatment and palliative care in advanced cases.

The study discusses the indications, results, and potential complications of using these radiation therapies alone or in combination with other treatments like androgen deprivation, highlighting their versatility in managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy for prostate cancer. Koontz, BF., Lee, WR.[2013]

References

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

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial. [2023]

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

Potential benefit of improved local tumor control in patients with prostate carcinoma. [2019]

3. India pubmed.ncbi.nlm.nih.gov

From two-dimensional to three-dimensional conformal radiotherapy in prostate cancer: an Indian experience. [2010]

4. Germany pubmed.ncbi.nlm.nih.gov

[The role of radiotherapy in locally limited prostate cancer]. [2006]

5. Germany pubmed.ncbi.nlm.nih.gov

Salvage radiotherapy in prostate cancer patients with biochemical relapse after radical prostatectomy : Prolongation of prostate-specific antigen doubling time in patients with subsequent biochemical progression. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

[Radiation therapy for prostate cancer]. [2011]

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

Assessing adverse events of postprostatectomy radiation therapy for prostate cancer: evaluation of outcomes in the Regione Emilia-Romagna, Italy. [2015]

8. Germany pubmed.ncbi.nlm.nih.gov

Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity : Case report and literature review. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

[Localized prostate cancer: Radiotherapeutic concepts]. [2018]

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

Trajectories and predictors of symptom occurrence, severity, and distress in prostate cancer patients undergoing radiation therapy. [2022]

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

Emerging technologies in prostate cancer radiation therapy: improving the therapeutic window. [2017]

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

Radiation therapy for prostate cancer: An evolving treatment modality. [2020]

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

Update on radiation-based therapies for prostate cancer. [2010]

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

Radiation therapy for prostate cancer. [2013]