Hormone Therapy + Radiation for Prostate Cancer

Recruiting at 617 trial locations

Overseen By William A. Hall

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must not be taking: Hormonal therapy, Anti-androgens

Disqualifiers: Metastatic disease, Prior malignancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 months

2050 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the effectiveness of different prostate cancer treatments based on the Decipher score, a specific genetic test. The study consists of two parts: one for patients at higher risk of cancer spreading and another for those at lower risk. Patients with a higher score will test whether adding darolutamide (a hormone therapy) to hormone therapy and radiation helps prevent cancer recurrence. Those with a lower score will determine if radiation alone is as effective as the usual combined treatment. Men with prostate cancer who haven't undergone major surgery or radiation to the prostate and meet certain medical criteria may qualify. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking any testosterone replacement therapy and 5-alpha-reductase inhibitors at least 30 days before joining. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research shows that the treatments in this trial—radiation therapy, darolutamide, and androgen deprivation therapy (ADT)—are generally well-tolerated by patients.

Radiation therapy is safe and effective for prostate cancer. It targets cancer cells while minimizing harm to nearby tissues, resulting in fewer side effects for many patients.

Darolutamide has shown promising results in other studies. It improved survival rates and was generally well-tolerated, with only a small number of patients needing to lower their dose due to side effects.

ADT helps fight cancer by lowering testosterone levels. It is widely used and has a known safety record. Some patients may experience side effects like hot flashes, but overall, it is considered safe.

In summary, studies suggest these treatments are safe for most patients. They have been widely studied and used, providing clear evidence of their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these prostate cancer treatments because they combine hormone therapy with radiation, potentially enhancing effectiveness. While standard treatments often involve just one approach, like radiation alone or hormone therapy, this study explores combining them for a one-two punch against cancer cells. The inclusion of darolutamide, a newer androgen receptor inhibitor, is particularly promising because it may provide a more targeted approach in blocking cancer cell growth compared to older therapies. By examining different combinations and delivery methods, these treatments could offer a more comprehensive way to manage prostate cancer with potentially fewer side effects.

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

Research has shown that radiation therapy, one of the treatments in this trial, effectively treats prostate cancer that hasn't spread. Studies indicate it can control the disease and prevent further spread. In this trial, some participants will receive radiation therapy alone, while others will receive it with hormone therapy. Specifically, using darolutamide with androgen deprivation therapy (ADT), which lowers male hormones, has greatly improved outcomes. One study demonstrated a 40% increase in the time patients live without cancer progression compared to standard treatments. Androgen deprivation therapy alone, another option in this trial, effectively reduces testosterone, helping to slow cancer growth. Together, these treatments offer promising results for prostate cancer patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Neil B Desai

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Men aged 18+ with unfavorable intermediate risk prostate cancer, specifically adenocarcinoma of the prostate, without prior treatments like radiotherapy or hormonal therapy to the pelvis. They must have a certain level of physical fitness (ECOG 0-2), adequate organ function, and no severe co-morbidities or high-risk features such as Gleason score 8-10 or metastatic disease.

Inclusion Criteria

Hemoglobin >= 8.0 g/dL within 120 days prior to registration

AST and ALT =< 2.5 x institutional ULN within 120 days prior to registration

I am HIV positive, on treatment, and my viral load is undetectable.

Exclusion Criteria

I have had radiation therapy to my prostate or pelvis area before.

High risk features

I have had both testicles surgically removed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive radiation therapy (RT) with or without androgen deprivation therapy (ADT) and darolutamide based on Decipher risk score

6 months

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Follow-up visits at 3, 6, 12, 24, 36, 48, and 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Bicalutamide
• Buserelin
• Darolutamide
• Degarelix
• Flutamide
• Goserelin
• Histrelin
• Leuprolide
• Radiation Therapy
• Relugolix
• Triptorelin

Trial Overview The trial is testing two approaches based on Decipher gene risk scores: less intense treatment (radiation alone) for low-risk patients versus more intense treatment (radiation plus hormone therapy and darolutamide) for higher-risk patients. Darolutamide blocks male hormones that can fuel cancer growth.

How Is the Trial Designed?

Group I: Arm IV (RT, ADT, darolutamide) Experimental Treatment 9 Interventions

Patients receive RT and ADT as in Arm II. Patients also receive darolutamide PO BID on days 1-90. Treatment repeats every 90 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm III (RT, ADT) Experimental Treatment 10 Interventions

Patients receive treatment as in Arm II.

Group III: Arm II (RT, ADT) Experimental Treatment 10 Interventions

Patients undergo RT as Arm I. Patients also receive androgen deprivation therapy (ADT) consisting of leuprolide, goserelin, buserelin, histrelin, triptorelin, degarelix, or relugolix at the discretion of the treating physician, for 6 months in the absence of disease progression or unacceptable toxicity. Patients may also receive bicalutamide or flutamide for 0, 30 or 180 days.

Group IV: Arm I (RT) Experimental Treatment 1 Intervention

Patients undergo radiation therapy (RT) using a recognized regimen (2-3 days a week or 5 days a week for 2-11 weeks) in the absence of disease progression or unacceptable toxicity.

Bicalutamide is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Casodex for:

• Metastatic prostate cancer

Approved in Japan as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 1,370 patients with locally advanced prostate cancer, bicalutamide 150 mg combined with radiotherapy significantly improved progression-free survival (PFS) by 44% and overall survival by 35% compared to radiotherapy alone, indicating its efficacy as an adjuvant therapy.

Bicalutamide also showed a substantial reduction in the risk of prostate-specific antigen (PSA) progression by 59%, making it a promising non-castration-based treatment option that offers quality-of-life benefits over traditional castration therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer. See, WA., Tyrrell, CJ.[2018]

In a study of 124 patients with advanced prostate cancer, bicalutamide showed an overall response rate of 50% to 61% across different doses, with the 80 mg dose demonstrating the highest efficacy in reducing prostate lesions and metastases.

Bicalutamide was found to be well tolerated, with a similar incidence of adverse reactions (around 61-65%) across all doses, and the most common side effects being gynecomastia and breast pain, leading to the conclusion that 80 mg once daily is the recommended dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer]. Kotake, T., Usami, M., Isaka, S., et al.[2015]

A combination treatment of 150 mg bicalutamide and 5 mg finasteride was effective in achieving undetectable PSA levels and improving quality of life in a 69-year-old patient with relapsed prostate cancer, demonstrating minimal side effects.

Laboratory experiments showed that this combination therapy inhibited cancer cell proliferation and reduced androgen receptor activity, potentially slowing the progression to hormone independence in prostate cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review. Wang, LG., Mencher, SK., McCarron, JP., et al.[2014]

In a study involving 1370 patients with early nonmetastatic prostate cancer, adjuvant therapy with bicalutamide (150 mg/d) significantly reduced the risk of disease progression by 37% compared to radiotherapy alone after a median follow-up of 3 years.

These preliminary results suggest that bicalutamide can provide additional benefits when used immediately after radiotherapy, indicating its potential as an effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate Treatment with Bicalutamide, 150 mg/d, Following Radiotherapy in Localized or Locally Advanced Prostate Cancer. Tyrrell, C.[2020]

Bicalutamide, when used in conjunction with radiation therapy, showed cytotoxic effects in androgen-dependent prostate cancer cells (LNCaP), leading to cell cycle arrest and reduced expression of prostate serum antigen (PSA) and androgen receptor (AR).

The study found that bicalutamide decreased the effectiveness of radiation in LNCaP cells, suggesting that it should not be administered close to radiation treatment to avoid antagonistic interactions, while showing an additive effect in androgen-independent DU145 cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells. Quéro, L., Giocanti, N., Hennequin, C., et al.[2014]

In a study of 6882 men with high-risk prostate cancer, the type of androgen suppression therapy (AST) used alongside radical radiotherapy (RRT) significantly influenced the risk of prostate cancer death, particularly when comparing combinations of bicalutamide and GnRH with different RRT types.

Men receiving monotherapy with bicalutamide combined with conventional fractionated external beam radiotherapy (CF-EBRT) had a notably higher risk of prostate cancer death (HR 2.35), while those treated with neoadjuvant CAB/adjuvant GnRH showed no increased risk, indicating the importance of therapy combinations in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists. Bonde, TM., Garmo, H., Stattin, P., et al.[2023]

Bicalutamide is a newly approved non-steroidal anti-androgen for prostate cancer treatment, showing strong affinity for androgen receptors and effective tumor suppression in pharmacological studies, leading to its approval in about 70 countries.

In a late Phase II study in Japan, bicalutamide achieved a response rate of 64.4% when used alone, highlighting its potential as a standalone treatment option that may enhance patient quality of life and sexual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer--basic clinical aspects]. Akaza, H.[2014]

In a study involving 3603 men with localized or locally advanced prostate cancer, bicalutamide significantly reduced the risk of disease progression by 43% compared to placebo after a median follow-up of 2.6 years.

Bicalutamide also delayed the time to prostate-specific antigen (PSA) doubling, indicating its efficacy in managing prostate cancer, although common side effects included gynecomastia and breast pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) 150 mg as immediate therapy in patients with localized or locally advanced prostate cancer significantly reduces the risk of disease progression. Wirth, M., Tyrrell, C., Wallace, M., et al.[2019]

In a study involving 1,218 patients with early prostate cancer, bicalutamide 150 mg significantly reduced the risk of disease progression by 57% compared to standard care alone, demonstrating its efficacy as an immediate therapy.

The study, with a median follow-up of 3 years, showed no difference in overall survival between bicalutamide and placebo, indicating that while it effectively delays disease progression, its impact on long-term survival is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6. Iversen, P., Tammela, TL., Vaage, S., et al.[2019]

In a study comparing hormonal treatments for prostate cancer before brachytherapy, goserelin showed a significant reduction in prostate volume (26%) compared to bicalutamide (8% reduction) and no hormonal treatment (8% increase).

Goserelin was found to be significantly more effective than bicalutamide in reducing prostate volume, suggesting that LHRH analogues like goserelin should be considered the gold standard for cytoreduction prior to brachytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is bicalutamide equivalent to goserelin for prostate volume reduction before radiation therapy? A prospective, observational study. Henderson, A., Langley, SE., Laing, RW.[2019]

Citations

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Relugolix for treating hormone-sensitive prostate cancer Clinical trial evidence suggests that relugolix is better at reducing testosterone to levels that stop cancer growth in the long term, and reduces the risk of ...

2. targetedonc.com targetedonc.com/view/considering-the-evolution-of-arpi-combination-therapy-in-mhspc

Considering the Evolution of ARPI Combination Therapy in ... This trial is for patients with confirmed prostate cancer with or without a first-generation antiandrogen, no prior second-generation ARPI. They ...

3. urologytimes.com urologytimes.com/view/rahul-aggarwal-md-highlights-phase-3-presto-findings-in-bcr-prostate-cancer

Rahul Aggarwal, MD, highlights phase 3 PRESTO findings ... ADT plus apalutamide and the triplet regimen also both showed improvements vs ADT monotherapy in the time to castration-resistant prostate ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.TPS283

NRG-GU011: A phase II double-blinded, placebo ... Relugolix allows for rapid testosterone recovery and is associated with fewer cardiovascular events when compared to leuprolide and is ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004325

Oral Relugolix for Androgen-Deprivation Therapy in ... Intermittent androgen-deprivation therapy that is monitored by means of PSA levels is a potential option for patients with prostate cancer, because studies have ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11988238/

Study of persistence and adherence to ADT in prostate ... Androgen deprivation therapy (ADT), a key treatment for advanced prostate cancer, lowers testosterone levels, a hormone that helps prostate ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0302283825004361

Short-term Androgen Deprivation Therapy and High-dose ... After 5 years of follow-up, patients who received short-term hormone therapy showed better cancer control outcomes without experiencing more ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02663908

Study Details | NCT02663908 | A Trial Comparing ... The purpose of this trial is to test if a marketed drug for advanced prostate cancer (FIRMAGON) can reduce the risk of cardiovascular complications as compared ...

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

6-month Formulations of Androgen Deprivation Therapy for ... The combination of efficacy, safety, and practicality offered by 6-month LHRH formulations may make them a preferred choice for patients and ...