Ultra-Hypo vs Conventional IMRT for Prostate Cancer

(PCS-XI Trial)

Not currently recruiting at 15 trial locations

Overseen By Josee Allard

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: CHU de Quebec-Universite Laval

Must be taking: ADT

Must not be taking: Alpha-blockers

Disqualifiers: Stage M1, Collagenosis, Inflammatory bowel, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2-5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different methods of delivering radiation therapy for prostate cancer. It aims to determine if a shorter, more intense schedule of radiation (ultra-hypo fractionation) is as effective as the longer, standard method (conventionally fractionated IMRT with HDR boost). Researchers will assess how patients tolerate the treatments and monitor any side effects, while also tracking survival rates and cancer control. Men diagnosed with prostate cancer who are at higher risk according to specific medical guidelines may be suitable candidates for this trial. As an unphased trial, it offers patients the chance to explore innovative treatment options that could potentially improve outcomes.

Will I have to stop taking my current medications?

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?

Studies have shown that ultrahypofractionated radiation therapy, similar to what is being tested in this trial, appears safe. Research indicates it is well-tolerated, with no increased risk of serious side effects. Specifically, individuals who received this type of radiation for prostate cancer did not experience more severe urinary or gastrointestinal issues compared to those on standard treatments. These findings suggest the treatment is promising for safety, but further research is necessary to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new radiation technique for prostate cancer treatment. Unlike the conventional approach, which involves 20-25 radiation sessions over several weeks, the ultra-hypofractionated radiotherapy (UHF) treatment delivers higher doses in just five sessions over two weeks. This means a significantly shorter treatment duration, which could lead to increased convenience and potentially fewer side effects for patients. By delivering radiation more intensively, UHF might also maintain or even enhance the effectiveness of prostate cancer treatment compared to standard methods.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that ultra-hypo fractionated radiotherapy (UHF), a treatment option in this trial, is both effective and safe for prostate cancer. Studies have found that UHF controls cancer as well as standard treatments, with similar long-term outcomes. This method involves fewer radiation sessions, delivering higher doses each time, which may be more convenient for patients. Reviews suggest that UHF effectively treats cancers that have spread to nearby lymph nodes, small glands that help fight infection. Studies also indicate that UHF has manageable side effects, with no severe issues for most patients. Overall, UHF appears to be a promising and safe option for treating prostate cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Andre-Guy Martin, MD MSc FRCPC

Principal Investigator

Andre-Guy Martin MD Inc.

Are You a Good Fit for This Trial?

This trial is for men with a specific type of prostate cancer that hasn't spread to other parts of the body. They should be at an intermediate to very high risk according to NCCN guidelines and have not had pelvic radiotherapy before. Men with autoimmune diseases like Lupus, past inflammatory bowel disease, advanced prostate cancer (stage M1), severe urinary symptoms even on medication, or bilateral hip replacements cannot join.

Inclusion Criteria

My cancer has not spread to distant parts of my body.

My condition is classified as intermediate to very high risk.

My cancer has a risk of spreading to lymph nodes needing pelvic radiation.

Exclusion Criteria

Bilateral hip prosthesis

I have a history of autoimmune diseases like Lupus.

I have a history of inflammatory bowel disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ultra-hypo fractionated radiotherapy (5 Gy/fraction) over 2 weeks or standard fractionation (1.8-2.15 Gy/fraction) over 4-5 weeks, combined with HDR brachytherapy and ADT

2-5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 3 months for 1 year, then every 6 months up to 36 months, and annually up to 10 years

10 years

Long-term Monitoring

Long-term monitoring of testosterone levels and other health metrics to assess disease-free survival and overall survival

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Conventionally Fractionated IMRT with HDR Boost
• HDR Prostate +/- Adjacent Seminal Vesicles Brachytherapy Boost (HDR-BT)
• Pelvic Nodes Ultra-Hypo Fractionated Radiotherapy (UHF)

Trial Overview

The study compares two types of radiation therapy: ultra-hypo fractionated radiotherapy delivering higher doses per session versus standard or moderate hypo-fractionation with lower doses per session. Both methods are combined with HDR brachytherapy boost and hormone therapy as per NCCN guidelines. The main goal is to see if the new method is just as good without causing more side effects.

How Is the Trial Designed?

Group I: ultra hypo fractionation radiation therapy (UHF) Experimental Treatment 8 Interventions

5 radiation treatments (5 Gy per fraction) to the prostate, seminal vesicle and pelvic nodes given every other day over 2 weeks for a total of 25 Gy.

Group II: standard of care fractionation (SOC) Active Control 8 Interventions

20-25 radiation treatments (range: 1,8 to 2,15 Gy per fraction) to the prostate, seminal vesicle and pelvic nodes given in 20-25 working day treatments over 4-5 weeks for a total of 43 Gy to 46 Gy.

Conventionally Fractionated IMRT with HDR Boost is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Intensity-Modulated Radiation Therapy with High-Dose Rate Brachytherapy Boost for:

• Prostate cancer

Approved in European Union as IMRT with HDR-BT for:

• Prostate cancer

Approved in Canada as Intensity-Modulated Radiation Therapy with High-Dose Rate Brachytherapy Boost for:

• Prostate cancer

Approved in Japan as IMRT with HDR-BT for:

• Prostate cancer

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

TerSera Therapeutics LLC

Industry Sponsor

Trials

11

Recruited

1,300+

Published Research Related to This Trial

In a clinical trial involving 42 men with intermediate-risk prostate cancer, a treatment combining a single 15 Gy HDR brachytherapy boost with a five-fraction external beam radiation therapy (EBRT) resulted in a high biochemical disease-free survival rate of 95.5% after a median follow-up of 36 months.

The treatment demonstrated low toxicity, with only one case of acute Grade 3 gastrointestinal and genitourinary toxicity, and no significant differences in health-related quality of life across urinary, bowel, or sexual domains, suggesting it is a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer. Den, RB., Greenspan, J., Doyle, LA., et al.[2023]

In a study of 148 prostate cancer patients treated with high-dose-rate (HDR) brachytherapy followed by intensity-modulated radiation therapy (IMRT), the treatment showed a high 4-year biochemical disease-free survival (bDFS) rate of 96.8% using the Phoenix criteria.

The treatment was well tolerated, with low rates of genitourinary (10%) and gastrointestinal (5%) toxicities, indicating that this combination therapy is both effective and safe for patients in a community setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-year outcomes of hypofractionated high-dose-rate prostate brachytherapy and external beam radiotherapy. Chen, WC., Tokita, KM., Ravera, J., et al.[2018]

In a study of 78 high-risk prostate cancer patients, treatment with normofractionated whole pelvic radiotherapy followed by a hypofractionated boost using intensity-modulated radiotherapy (IMRT) showed excellent tolerance, with only 1% experiencing severe acute toxicity and no patients reporting grade 4 toxicity.

With a median follow-up of 57 months, the treatment resulted in high rates of disease control, including an 84.5% biochemical disease-free survival rate, indicating that this approach is effective for managing non-metastatic prostate cancer at high risk of lymph node involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated external beam radiotherapy to boost the prostate with ≥85 Gy/equivalent dose for patients with localised disease at high risk of lymph node involvement: feasibility, tolerance and outcome. Zilli, T., Jorcano, S., Escudé, L., et al.[2018]

High-dose-rate brachytherapy (HDR-BT) delivers a significantly higher dose to the planning target volume (PTV) compared to both robotic and conventional stereotactic body radiotherapy (SBRT), indicating its potential for more effective treatment of prostate cancer.

HDR-BT results in lower radiation exposure to the bladder and rectum than SBRT, which may reduce the risk of side effects, although it does expose the urethra to a higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer. Yoshioka, Y., Sasamura, K., Ito, M., et al.[2023]

In a study comparing 253 patients treated with ultrahypofractionated radiotherapy (UHF) and 499 patients with dose-escalated conventional to moderate hypofractionated radiotherapy (DeRT), high-dose UHF was associated with higher rates of late gastrointestinal and genitourinary toxicity compared to both low-dose UHF and DeRT.

Despite the increased toxicity with high-dose UHF, both low-dose UHF and DeRT showed similar efficacy in terms of biochemical failure-free survival rates, suggesting that low-dose UHF (EQD2 ≤ 100 Gy1.5) is a promising treatment option with a favorable balance of safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrahypofractionated Radiotherapy versus Conventional to Moderate Hypofractionated Radiotherapy for Clinically Localized Prostate Cancer. Yamazaki, H., Suzuki, G., Aibe, N., et al.[2022]

In a pilot study involving 24 patients with low- to intermediate-risk prostate cancer, highly hypofractionated intensity modulated radiation therapy (IMRT) delivered 54 Gy in 15 fractions over 3 weeks resulted in high survival rates: 91.7% biochemical relapse-free survival and 95.8% overall survival at 5 years.

The treatment was well-tolerated, with no severe late gastrointestinal or grade ≥3 genitourinary toxicities observed, suggesting that this approach may be a safe and effective alternative to traditional radiation therapy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks. Nakamura, K., Ikeda, I., Inokuchi, H., et al.[2023]

High dose rate (HDR) interstitial brachytherapy offers a significantly better therapeutic ratio compared to conventional intensity modulated radiation therapy (IMRT) for prostate cancer treatment, based on a study involving nine patients.

The study found that HDR boosts are comparable to or even better than biologically equivalent fractionated IMRT boosts, particularly when considering idealized image-guided delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of HDR brachytherapy and IMRT techniques for dose escalation in prostate cancer: a radiobiological modeling study. Fatyga, M., Williamson, JF., Dogan, N., et al.[2022]

Extreme hypofractionation, which involves delivering large doses of radiation in fewer sessions, may be particularly effective for prostate cancer due to the tumor's low sensitivity to radiation and high ability to repair damage.

Both high-dose rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are promising methods for this approach, but further research is needed to ensure effective dose distribution and minimize treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for prostate cancer: treatment approaches and clinical outcomes. Miralbell, R.[2020]

Accelerated hypofractionated external beam radiotherapy combined with high-dose rate brachytherapy effectively delivered high radiation doses to prostate cancer patients, achieving high overall survival and biochemical control rates over an 8-year follow-up period.

Adding up to 6 months of androgen deprivation therapy did not improve outcomes and was associated with increased rates of metastasis and cancer-related deaths, raising concerns about its use in conjunction with high-dose radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of benefit from a short course of androgen deprivation for unfavorable prostate cancer patients treated with an accelerated hypofractionated regime. Martinez, AA., Demanes, DJ., Galalae, R., et al.[2018]

In the HYPO-RT-PC trial involving 1180 patients with localized prostate cancer, ultra-hypofractionated radiotherapy showed higher acute toxicity compared to conventional fractionation, particularly in bowel symptoms, but long-term quality of life (QOL) was similar between the two treatment methods up to 6 years post-treatment.

Despite the initial increase in bowel-related issues for patients receiving ultra-hypofractionation, there were no significant differences in urinary, bowel, or sexual functioning between the two groups after the treatment period, indicating that ultra-hypofractionation is a viable option for patients with intermediate-to-high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial. Fransson, P., Nilsson, P., Gunnlaugsson, A., et al.[2021]

In a study of 41 patients with high-risk localized prostate cancer, combining whole-pelvis irradiation with a stereotactic body radiotherapy (SBRT) boost resulted in a high 4-year biochemical failure-free survival rate of 91.9%, indicating effective cancer control.

The treatment was associated with minimal toxicity, with no severe (grade 3) gastrointestinal or genitourinary side effects reported, suggesting that this approach is safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The early result of whole pelvic radiotherapy and stereotactic body radiotherapy boost for high-risk localized prostate cancer. Lin, YW., Lin, LC., Lin, KL.[2020]

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