Androgen Deprivation Therapy for Prostate Cancer

(RATIONAL Trial)

Not yet recruiting at 1 trial location

Overseen By Lisa Rudd-Scott

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Ontario Clinical Oncology Group (OCOG)

Must not be taking: ADT, Chemotherapy

Disqualifiers: Age < 18, ECOG ≥3, PSA ≥ 20, 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

Compensation: Varies

Number of Visits: 6

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding ELIGARD® (a form of androgen deprivation therapy) to current therapy can help patients with hormone-sensitive prostate cancer, which has recurred after radiation, avoid further disease progression. The study compares two approaches: one group receives ELIGARD® alongside their standard treatment for a year, while the other group continues with only the standard treatment. It targets those whose prostate cancer has returned but has not spread to more than five new areas and who have not recently undergone hormone therapy. Participants will attend follow-up visits every three months for three years. 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 does not specify if you need to stop taking your current medications. However, you cannot have had Androgen Deprivation Therapy (ADT) within 2 years or any androgen receptor treatment within 6 months before joining the study.

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

Research has shown that ELIGARD®, the treatment used in this trial, is safe for patients with hormone-dependent prostate cancer. In past studies, most participants tolerated ELIGARD® well. Common side effects included minor reactions at the injection site and hot flashes. These side effects were not serious and typically resolved quickly. One report noted moderate pain that disappeared within two minutes. Overall, previous studies have proven the treatment safe, and it is already approved for similar conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about ELIGARD for prostate cancer because it offers a unique approach by combining androgen deprivation therapy (ADT) with recurrence-directed therapy (RDT) for a full year. Unlike standard treatments that often involve ADT alone, this combination targets not just systemic hormonal suppression but also local and regional cancer sites, potentially improving outcomes for patients with oligometastatic disease. ELIGARD is a formulation of leuprolide acetate, which uses an innovative delivery system to provide consistent hormone suppression over time, aiming for more effective long-term control of prostate cancer progression. This dual approach could be a game-changer in managing recurrent prostate cancer.

What evidence suggests that ELIGARD might be an effective treatment for prostate cancer?

Studies have shown that ELIGARD® effectively treats prostate cancer by lowering testosterone levels, which is crucial for managing the disease. Research indicates that most patients using ELIGARD® reached very low testosterone levels by the second dose. This is important because prostate cancer often grows with the help of testosterone. In this trial, one group of participants will receive Recurrence-directed therapy (RDT) in addition to ELIGARD® treatment for 12 months. Other studies have consistently demonstrated ELIGARD®'s safe use across different groups of people. These findings suggest that ELIGARD® is a promising option for controlling prostate cancer by effectively reducing testosterone levels. ^{1 2 6 7 8}

Who Is on the Research Team?

Theos Tsakiridis, Dr.

Principal Investigator

McMaster University

Jim Wright, Dr.

Principal Investigator

Ontario Clinical Oncology Group (OCOG)

Are You a Good Fit for This Trial?

This trial is for men with early-stage, hormone-sensitive prostate cancer that has come back after radiation therapy. They should have a small number of metastases and not be on any current hormone treatments. Key exclusions include allergies to the study drug or its components.

Inclusion Criteria

My prostate cancer has returned with 5 or fewer spots of spread, not visible on standard scans.

I had prostate cancer treated with radiation over 2 years ago.

All my cancer recurrences can be treated with surgery or radiation.

Exclusion Criteria

I am under 18 years old.

PSA ≥ 20 ng/ml

I do not have cancer spread to my spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Recurrence-Directed Therapy (RDT) with or without Androgen-Deprivation Therapy (ADT) for 12 months

12 months

Standard of care clinic visits every 3 months

Follow-up

Participants are monitored for disease progression, overall survival, and quality of life

36 months

Scheduled follow-up visits at 3, 6, 15, and 36 months

What Are the Treatments Tested in This Trial?

Interventions

• ELIGARD

Trial Overview The study is testing if adding Androgen Deprivation Therapy (ADT) using ELIGARD to Recurrence-Directed Therapy (RDT) can extend the time without cancer progression compared to RDT alone in these patients.

How Is the Trial Designed?

Group I: Recurrence-directed therapy (RDT) + ADT x 12 months Experimental Treatment 2 Interventions

Local, regional or distant oligometastatic RDT in addition to treatment with ADT for 12 months in the form of ELIGARD®.

Group II: Recurrence-directed therapy (RDT) alone Active Control 1 Intervention

Local, regional, and distant oligometastatic RDT.

Who Is Running the Clinical Trial?

Ontario Clinical Oncology Group (OCOG)

Lead Sponsor

Trials

65

Recruited

42,000+

Ontario Clinical Oncology Group (OCOG) - McMaster University

Collaborator

Trials

1

Recruited

160+

TOLMAR PHARMACEUTIQUES CANADA, INC.

Collaborator

Trials

1

Recruited

160+

Published Research Related to This Trial

In the SPARTAN study, apalutamide combined with androgen deprivation therapy (ADT) led to rapid and significant reductions in prostate-specific antigen (PSA) levels in most patients, with 90% achieving at least a 50% reduction by 6 months, compared to only 1.5% in the placebo group.

Deep PSA responses (≥90% reduction or PSA ≤0.2 ng/ml) at 6 months were strongly linked to improved outcomes, including metastasis-free survival and overall survival, indicating that early PSA monitoring can be a valuable prognostic tool for patients with high-risk nonmetastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. Saad, F., Small, EJ., Feng, FY., et al.[2022]

Exercise is strongly supported as an effective strategy to manage several adverse effects of androgen deprivation therapy (ADT) in prostate cancer patients, including loss of muscle mass, fatigue, and declining physical function.

In addition to physical benefits, exercise may also improve mental health outcomes such as depression and anxiety, suggesting it plays a crucial role in enhancing overall quality of life and survivorship for men undergoing ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of exercise in the management of adverse effects of androgen deprivation therapy for prostate cancer: a rapid review. Edmunds, K., Tuffaha, H., Scuffham, P., et al.[2021]

Androgen deprivation therapy (ADT) for prostate cancer can lead to significant adverse effects, including loss of libido, fatigue, and increased risks for fractures, diabetes, and cardiovascular disease, particularly in older men who are already vulnerable.

There is a critical need for primary care clinicians to implement screening and preventive measures for these treatment-related health issues in prostate cancer survivors, using evidence-based guidelines adapted from those for the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer survivorship: prevention and treatment of the adverse effects of androgen deprivation therapy. Saylor, PJ., Keating, NL., Smith, MR.[2021]

In a study involving 385 patients with non-castrate metastatic prostate cancer, it was found that physicians significantly under-reported adverse symptoms related to androgen deprivation therapy (ADT), with agreement rates for common symptoms like hot flushes and fatigue being only around 50-64%.

The failure of physicians to report patients' most disturbing symptoms ranged from 50.8% to 89.5%, highlighting the importance of incorporating patients' self-reports in clinical trials to better assess treatment toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' self-assessment versus investigators' evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15). Gravis, G., Marino, P., Joly, F., et al.[2019]

Androgen deprivation therapy (ADT) is effective for managing symptoms of prostate cancer but can lead to significant side effects that worsen over time, and it does not improve survival in men with localized disease.

Neoadjuvant ADT combined with external beam radiation has been shown to enhance survival in men with locally advanced prostate cancer, while immediate adjuvant ADT does not provide benefits for most men after radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The timing and extent of androgen deprivation therapy for prostate cancer: weighing the clinical evidence. Ginzburg, S., Albertsen, PC.[2019]

In a novel approach, four heavily pretreated Japanese patients with castration-resistant prostate cancer showed clinical responses to high doses of testosterone, challenging traditional androgen deprivation therapy.

One of the patients treated was on hemodialysis, indicating that this treatment may be applicable even in complex medical situations, suggesting a potential new avenue for therapy in difficult cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical response in metastatic castration-resistant prostate cancer (mCRPC) cases treated with supra-physiological doses of testosterone: Bipolar androgen therapy. Hoshi, S., Bilim, V., Hoshi, K., et al.[2023]

In the SPARTAN study involving 247 patients with nonmetastatic castration-resistant prostate cancer, the addition of apalutamide to androgen-deprivation therapy significantly improved metastasis-free survival and overall survival without increasing detectable androgen receptor or other genomic aberrations compared to ADT alone.

At the end of the study, higher levels of circulating-tumor DNA (ctDNA) and specific genetic aberrations (like AR, TP53, and BRCA2) were linked to worse outcomes, indicating that these biomarkers could help predict patient prognosis after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Biomarker Landscape in Patients with High-risk Nonmetastatic Castration-Resistant Prostate Cancer Treated with Apalutamide and Androgen-Deprivation Therapy as They Progress to Metastatic Disease. Smith, MR., Thomas, S., Gormley, M., et al.[2022]

In the SPARTAN study, apalutamide significantly improved overall survival (OS) in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), showing a 25% reduction in the risk of death compared to placebo after a median follow-up of 41 months.

Apalutamide also enhanced second progression-free survival (PFS2) by 45%, indicating its efficacy in delaying disease progression, with no new safety concerns reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Small, EJ., Saad, F., Chowdhury, S., et al.[2023]

Citations

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

Efficacy in Prostate Cancer Analysis includes 424 patients who achieved castrate T levels by the second dose on the 1-month (n=113), 3-month (n=115), 4-month (n=88), and 6- ...

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

ELIGANT: a Phase 4, interventional, safety study of ... The safety profile of ELIGARD® (22.5 mg) in Asian men with hormone-dependent prostate cancer is comparable to previous studies in Western regions.

3. openurologyandnephrologyjournal.com openurologyandnephrologyjournal.com/VOLUME/17/ELOCATOR/e1874303X237036/FULLTEXT/

6-month Formulations of Androgen Deprivation Therapy for ... A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method:.

4. frontierspartnerships.org frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2024.12473/full

Clinical efficacy of different androgen deprivation therapies for ... This study evaluated the clinical efficacy of different androgen deprivation therapies in the treatment of PCa from the perspective of DCE-MRI

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Five-year follow-up analyses demonstrated that 34% of the metastasis-directed therapy (MDT) group remain ADT-free at 5 years, in contrast to 8% ...

6. 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 ...

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

Real world data of leuprorelin castration efficacy in patients ... HERO phase III trial: Results comparing relugolix, an oral GnRH receptor antagonist, versus leuprolide acetate for advanced prostate cancer.

8. 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 ... Ninety-two patients (37.86%) experienced treatment-emergent adverse events, with injection site-related reactions, hot flushes and tumor flare being the most ...