Androgen Deprivation Therapy for Prostate Cancer

(RATIONAL Trial)

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

162 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to determine whether the addition of Androgen Deprivation Therapy (ADT) utilizing the study drug ELIGARD® to Recurrence- Directed Therapy (RDT) improves progression-free survival (PFS) compared to RDT alone in patients with early radio-recurrent oligo-metastatic castrate / hormone sensitive prostate cancer (romCSPC). Participants will be assessed at standard of care clinic visits every 3 months. The follow-up period is 36 months.

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.

What data supports the effectiveness of the drug ELIGARD for prostate cancer?

The research highlights that androgen deprivation therapy (ADT), which ELIGARD is a part of, is effective in treating prostate cancer by suppressing testosterone levels, which are important for cancer growth. Studies show that adding other drugs like apalutamide to ADT can improve survival and delay disease progression in prostate cancer patients. ^{1 2 3 4 5}

Is androgen deprivation therapy (ADT) generally safe for humans?

Androgen deprivation therapy (ADT) for prostate cancer is associated with several adverse effects, including bone loss, increased fracture risk, changes in body composition that may lead to diabetes, and increased cardiovascular risk. These side effects are important to consider when evaluating the safety of ADT. ^{6 7 8 9 10}

How does the drug ELIGARD differ from other treatments for prostate cancer?

ELIGARD is a form of androgen deprivation therapy that uses a gonadotropin-releasing hormone (GnRH) agonist to lower testosterone levels, which is different from surgical castration or using antiandrogens alone. It is administered as an injection, which can be more convenient compared to daily oral medications. ^{11 12 13 14 15}

Research Team

Theos Tsakiridis, Dr.

Principal Investigator

McMaster University

Jim Wright, Dr.

Principal Investigator

Ontario Clinical Oncology Group (OCOG)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. [2023]

2. Switzerland 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. [2022]

3. United States 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. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

[Current status of androgen deprivation therapy in hormone-sensitive prostate cancer.] [2018]

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

Gain of androgen receptor gene copies in primary prostate cancer due to X chromosome polysomy. [2006]

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

Prostate cancer survivorship: prevention and treatment of the adverse effects of androgen deprivation therapy. [2021]

7. Germany 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. [2021]

8. England 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). [2019]

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

Management of bone and metabolic effects of androgen deprivation therapy. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Prostate cancer: cardiovascular mortality and androgen deprivation. [2021]

11. Spain pubmed.ncbi.nlm.nih.gov

External beam radiation therapy for clinically localized prostate cancer: when and how we optimize with concurrent hormonal deprivation. [2011]

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

Update on hormone-refractory prostate cancer. [2019]

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

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

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

Bicalutamide dosages used in the treatment of prostate cancer. [2019]

15. England 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. [2023]