Hypofractionated Radiation Therapy + Eligard for Prostate Cancer

(PROMPT Trial)

Recruiting at 2 trial locations

Overseen By Fabio Cury, MD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for men with prostate cancer who have undergone surgery but still face high risks of recurrence. It combines hypofractionated radiation therapy with a hormonal therapy called Eligard (leuprolide acetate), which may lower the chance of cancer returning. This trial suits those who have had prostate surgery and exhibit high-risk features, such as rising PSA levels (a protein indicating prostate cancer activity) or cancer found at the edges of removed tissue. Participants will receive Eligard injections before and during their radiation treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found Eligard, a hormone therapy, to be safe for men with prostate cancer. Some patients experienced mild to moderate pain at the injection site, but this was short-lived. Other common side effects included hot flashes and temporary increases in tumor activity.

Research has shown that hypofractionated radiation therapy, a shorter treatment plan, is also safe. Studies indicate it does not cause more side effects than traditional radiation. It is just as effective and well-tolerated as longer treatments.

Both treatments have been studied and found safe for patients with prostate cancer, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for prostate cancer because it combines hypofractionated radiation therapy with Eligard, a hormonal therapy, in a novel way. Unlike standard radiation treatments that are often given over several weeks, hypofractionated radiation delivers higher doses over a shorter period, potentially reducing treatment time. Eligard, which lowers testosterone levels to slow cancer growth, is administered before and during radiation, possibly enhancing the effectiveness of the radiation therapy. This approach aims to improve outcomes for patients who have undergone prostatectomy and are at high risk of recurrence.

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

This trial will evaluate the combination of Postoperative Hypofractionated Radiation Therapy and Eligard for prostate cancer. Studies have shown that a shorter course of radiation therapy after surgery is as safe and effective as traditional, longer treatments for prostate cancer. It improves survival rates without increasing the risk of urinary or digestive side effects. Research on Eligard, a hormone therapy, has shown that it significantly lowers levels of prostate-specific antigen (PSA) and testosterone, which are crucial in controlling prostate cancer growth. Together, these treatments offer a promising approach for managing prostate cancer in men with high-risk features. ^{2 3 4 6 7}

Who Is on the Research Team?

Fabio Cury, MD

Principal Investigator

Radiation Oncologist

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Tolmar Inc.

Industry Sponsor

Trials

5

Recruited

1,400+

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

Published Research Related to This Trial

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]

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 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 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 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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4107255/

Efficacy and tolerability of 1- and 3-month leuprorelin ... In this study, median total serum PSA and testosterone levels had decreased by 94% (from 11.6 ng/ml to 0.7 ng/ml) and 89% (from 89 ng/dl to 10 ng/dl) 6 months ...

2. eligardhcp.com eligardhcp.com/proven-efficacy-safety/

ELIGARD® (Leuprolide Acetate) | Efficacy in Prostate Cancer A single event reported as moderate pain resolved within 2 minutes and all 3 mild pain events resolved within several days following injection ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e17000

Real world data of leuprorelin castration efficacy in patients ... In this real-world study, we thoroughly analyzed data of testosterone tests in order to comprehensively assess the leuprorelin castration efficacy on the PCa ...

4. archivesofmedicalscience.com archivesofmedicalscience.com/Clinical-research-Efficacy-and-tolerability-of-1-and-3-month-leuprorelin-acetate,53288,0,2.html

and 3-month leuprorelin acetate depot formulations ... Patients were followed for at least 3 months. Results: Median serum prostate-specific antigen levels were reduced by 95% from 12.0 ng/ml at baseline to 0.60 ng/ ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01415960

Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in ... Leuprolide Acetate 22.5 mg Depot is a microencapsulated formulation of leuprolide which is released slowly over time and effectively reduces testosterone levels ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8899139/

ELIGANT: a Phase 4, interventional, safety study of ... The results of the ELIGANT study demonstrate that ELIGARD® 22.5 mg has an acceptable safety profile in men with hormone-dependent prostate cancer in Asia. There ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22025196/

Efficacy and safety of leuprolide acetate 6-month depot for ... Leuprolide acetate 45 mg 6-month depot demonstrated rapid and sustained testosterone suppression through 12 months and was well tolerated.