Hypofractionated Radiation Therapy + Eligard for Prostate Cancer

(PROMPT Trial)

Recruiting at 1 trial location

Overseen By Marianna Perna, CCRP

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Luis Souhami

Must not be taking: Androgen deprivation, Chemotherapy

Disqualifiers: Prior pelvic radiotherapy, Previous malignancies, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

77 Participants Needed

Trial Summary

What is the purpose of this trial?

Prostate cancer is the second most common cancer among Canadian men of which approximately 20-30% present with high-risk tumour characteristic. Although surgery can be curative in patients evidencing pathological high-risk disease (extracapsular extension, seminal vesicle involvement, positive surgical margins), a large proportion will develop biochemical failure within years from the surgical procedure. The failure rate is even more pronounced in those patients that present with high prostate specific antigen (PSA) levels, pT3 disease, positive margins and Gleason score ≥8 with an estimated 75% failure rate at 10 years. Post-operative radiotherapy (RT) has been shown in three randomized trials to significantly decrease the biochemical failure rate and in one of the trials a survival benefit was also seen with the addition of post-operative RT and is considered by many investigators standard therapy in patients with pathological high-risks factors even in absence of biochemical failure.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have had previous exposure to androgen deprivation or chemotherapy, you would not be eligible to participate.

What data supports the effectiveness of the treatment Hypofractionated Radiation Therapy + Eligard for Prostate Cancer?

Research shows that hypofractionated radiation therapy, which involves giving larger doses of radiation over fewer sessions, is being studied for its safety and effectiveness in treating prostate cancer after surgery. While there is limited data specifically for postoperative settings, early studies suggest it is a feasible option. ^{1 2 3 4 5}

Is hypofractionated radiation therapy with Eligard safe for prostate cancer patients?

Research shows that hypofractionated radiation therapy, often used after prostate surgery, is generally safe, though it can cause some side effects. These side effects can be both short-term (acute) and long-term (late), but the treatment is considered feasible and safe when combined with hormonal therapy like Eligard. ^{1 3 5 6 7}

How is hypofractionated radiation therapy with Eligard different from other prostate cancer treatments?

Hypofractionated radiation therapy involves giving higher doses of radiation over fewer sessions, which can be more convenient and potentially just as effective as traditional methods. This approach is being explored for use after prostate surgery, where data is still limited, making it a novel option compared to standard postoperative treatments. ^{1 3 5 8 9}

Research Team

Luis Souhami, MD

Principal Investigator

Radiation Oncologist

Eligibility Criteria

Men over 18 with high-risk prostate cancer post-prostatectomy, having negative lymph nodes and no bone metastases. Eligible participants must have a stable blood count, normal liver function, and not received prior pelvic radiotherapy or hormone therapy. They should be in good physical condition (Zubrod Performance Status 0-1) and free from severe medical conditions that could interfere with the study.

Inclusion Criteria

I had prostate surgery, my cancer hasn't spread to lymph nodes, and my PSA is rising but below 2.0 ng/ml.

My blood counts meet the required levels for treatment.

Patients must sign a study-specific consent form

Exclusion Criteria

I have a severe health condition that makes study treatments unsafe for me.

I have received chemotherapy before or after surgery to remove my prostate.

I have had radiation therapy to my pelvic area before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neo-adjuvant Hormonal Therapy

Participants receive one injection of neo-adjuvant hormonal therapy starting 12 weeks before radiation therapy

12 weeks

Hypofractionated Radiation Therapy

Participants receive hypofractionated radiation therapy for four weeks concurrently with another injection of LHRH analog

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments collected up to 5 years

5 years

Treatment Details

Interventions

• Eligard
• Postop Hypofractionated Radiation Therapy

Trial Overview The trial is testing the effectiveness of postoperative hypofractionated radiation therapy combined with LHRH agonist therapy using Eligard in men who've had surgery for high-risk prostate cancer. It aims to see if this combination can reduce the risk of cancer returning by monitoring PSA levels.

Participant Groups

Group I: Post-op IMRT & hormonal therapy Experimental Treatment 1 Intervention

The protocol is designed to recruit patients who have undergone prostatectomy and high risk features of the disease were found post-operatively or for patients that, after prostatectomy, a PSA rise has been documented will be enrolled in the Phase II trial. Patients will receive Eligard injection 8-12 weeks before starting radiation. The second injection is given 12 weeks after the first one concomitant with radiation therapy.

Postop Hypofractionated Radiation Therapy is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Postoperative Hypofractionated Radiation Therapy for:

• Prostate cancer with high-risk tumor characteristics
• Pathological high-risk disease post-surgery

Approved in United States as Postoperative Hypofractionated Radiation Therapy for:

• Prostate cancer with extracapsular extension
• Prostate cancer with seminal vesicle involvement
• Prostate cancer with positive surgical margins

Approved in European Union as Postoperative Hypofractionated Radiation Therapy for:

• High-risk prostate cancer post-surgery
• Biochemical failure prevention post-surgery

Who Is Running the Clinical Trial?

Luis Souhami

Lead Sponsor

Trials

1

Recruited

80+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

In a phase 2 trial involving 64 patients who underwent radical prostatectomy, postoperative hypofractionated radiation therapy (RT) to the prostate bed was found to be safe, with only 11.5% experiencing acute genitourinary (GU) grade ≥2 toxicity and 13.1% experiencing acute gastrointestinal (GI) grade ≥2 toxicity.

After a median follow-up of 16 months, the treatment showed promising outcomes with a 2-year biochemical failure-free survival rate of 95.1%, indicating its potential efficacy in preventing cancer recurrence, although further large-scale studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Radiation Therapy to the Prostate Bed With Intensity-Modulated Radiation Therapy (IMRT): A Phase 2 Trial. Leite, ETT., Ramos, CCA., Ribeiro, VAB., et al.[2021]

In a phase I/II study involving 30 patients treated with hypofractionated radiotherapy after prostate surgery, the treatment was well tolerated, with over 80% of patients experiencing low-grade acute toxicity and only 6% experiencing moderate to severe late toxicity.

The initial results showed promising PSA control, with only 17% of patients experiencing PSA failure after a median follow-up of 24 months, indicating potential efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated hypofractioned postoperative radiotherapy for prostate cancer: a prospective phase I/II study. Gladwish, A., Loblaw, A., Cheung, P., et al.[2015]

In a phase 2 trial involving 40 patients, postoperative hypofractionated intensity-modulated radiation therapy (IMRT) for prostate cancer showed favorable safety, with no severe adverse events (grade ≥3) reported.

Acute gastrointestinal (GI) toxicity was observed in 56.4% of patients (grade 1) and 17.9% (grade 2), while genitourinary (GU) toxicity was noted in 35.9% (maximum grade 1), indicating that the treatment is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated IMRT of the prostate bed after radical prostatectomy: acute toxicity in the PRIAMOS-1 trial. Katayama, S., Striecker, T., Kessel, K., et al.[2018]

In a study of 124 patients with high-risk prostate cancer, hypofractionated radiotherapy using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) showed a low incidence of severe acute toxicity, with only 1.6% of patients experiencing grade 3 or higher side effects.

The treatment resulted in a promising five-year biochemical relapse-free survival rate of 86.5%, indicating its efficacy in preventing cancer recurrence after radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study. Macchia, G., Siepe, G., Capocaccia, I., et al.[2021]

This phase II trial aims to evaluate the safety and feasibility of hypofractionated radiotherapy in 80 prostate cancer patients, focusing on the prostate bed and pelvic lymph nodes, with a total dose of 54 Gy in 18 fractions for the prostate bed and an additional 45 Gy for high-risk patients.

The study will provide valuable data on the effectiveness of hypofractionated treatment in postoperative settings, which is currently limited, and will utilize advanced techniques like Helical Tomotherapy and daily image guidance to enhance treatment precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated helical intensity-modulated radiotherapy of the prostate bed after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial. Krause, S., Sterzing, F., Neuhof, D., et al.[2021]

In a study of 105 patients with high-risk prostate cancer, the combination of androgen deprivation therapy (ADT) and moderate hypofractionated radiation therapy (HypoRT) was found to be well tolerated, with low rates of acute and late toxicity; only 17% experienced grade 2 or higher gastrointestinal or genitourinary toxicity, and no severe grade 4 or 5 toxicities were reported.

The treatment regimen resulted in an 82% progression-free survival rate at 48 months, demonstrating its efficacy while also shortening the overall treatment duration, making it a convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated pelvic radiation therapy. Faria, S., Ruo, R., Cury, F., et al.[2018]

In a study of 64 prostate cancer patients undergoing radical prostatectomy, hypofractionated radiotherapy (RT) demonstrated a high overall survival rate of 98% at 2 years and 96% at 5 years, with manageable acute and late toxicities.

The combination of hypofractionated RT with hormonal therapy (HT) was well tolerated and did not significantly increase toxicity, suggesting it can be safely used in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate hypofractionated radiotherapy after prostatectomy for cancer patients: toxicity and clinical outcome. Barra, S., Belgioia, L., Marcenaro, M., et al.[2020]

Hypofractionated proton therapy (PT) for prostate cancer is feasible and shows an acceptable toxicity profile, with acute gastrointestinal (GI) toxicity at 0% and acute genitourinary (GU) toxicity at 5% among 82 patients studied over a median follow-up of 42 months.

The four-year biochemical control free survival (BCFFS) rates were 85% and 86%, indicating that hypofractionated PT is as effective as conventional treatments, potentially offering patients a more efficient and cost-effective option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of hypofractionated proton therapy for prostate cancer. Kim, YJ., Cho, KH., Pyo, HR., et al.[2022]

In a study of 855 prostate cancer patients treated post-surgery, hypofractionated radiotherapy (HF) showed similar biochemical control rates and overall survival compared to conventionally fractionated radiotherapy (CF), indicating that both treatment methods are equally effective.

Patients receiving HF experienced significantly fewer acute gastrointestinal and genitourinary side effects, suggesting that HF may be a safer option in terms of immediate toxicity after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of moderate hypofractionation with volumetric modulated arc therapy versus conventional 3D-radiotherapy after radical prostatectomy. Moll, M., D'Andrea, D., Zaharie, A., et al.[2022]

References

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

Hypofractionated Radiation Therapy to the Prostate Bed With Intensity-Modulated Radiation Therapy (IMRT): A Phase 2 Trial. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Accelerated hypofractioned postoperative radiotherapy for prostate cancer: a prospective phase I/II study. [2015]

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

Hypofractionated IMRT of the prostate bed after radical prostatectomy: acute toxicity in the PRIAMOS-1 trial. [2018]

4. Greece pubmed.ncbi.nlm.nih.gov

Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Hypofractionated helical intensity-modulated radiotherapy of the prostate bed after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial. [2021]

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

Acute and late toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated pelvic radiation therapy. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Moderate hypofractionated radiotherapy after prostatectomy for cancer patients: toxicity and clinical outcome. [2020]

8. England pubmed.ncbi.nlm.nih.gov

A phase II study of hypofractionated proton therapy for prostate cancer. [2022]

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

Comparative effectiveness of moderate hypofractionation with volumetric modulated arc therapy versus conventional 3D-radiotherapy after radical prostatectomy. [2022]