Hormone Therapy + Radiation for Prostate Cancer

Recruiting at 572 trial locations

Overseen By William A. Hall

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: NRG Oncology

Must not be taking: Hormonal therapy, Anti-androgens

Disqualifiers: Metastatic disease, Prior malignancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase III trial uses the Decipher risk score to guide therapy selection. Decipher score is based on the activity of 22 genes in prostate tumor and may predict how likely it is for recurrent prostate cancer to spread (metastasize) to other parts of the body. Decipher score in this study is used for patient selection and the two variations of treatment to be studied: intensification for higher Decipher score or de-intensification for low Decipher score. Patients with higher Decipher risk score will be assigned to the part of the study that compares the use of 6 months of the usual treatment (hormone therapy and radiation treatment) to the use of darolutamide plus the usual treatment (intensification). The purpose of this section of the study is to determine whether the additional drug can reduce the chance of cancer coming back and spreading in patients with higher Decipher score. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading. Alternatively, patients with low Decipher risk score will be assigned to the part of the study that compares the use of radiation treatment alone (de-intensification) to the usual approach (6 months of hormone therapy plus radiation). The purpose of this part of the study is to determine if radiation treatment alone is as effective compared to the usual treatment without affecting the chance of tumor coming back in patients with low Decipher score prostate cancer. Radiation therapy uses high energy to kill tumor cells and reduce the tumor size. Hormone therapy drugs such as darolutamide suppress or block the production or action of male hormones that play role in prostate cancer development. Effect of radiation treatment alone in patients with low Decipher score prostate cancer could be the same as the usual approach in stabilizing prostate cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy.

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.

What data supports the effectiveness of the drug Bicalutamide when used with radiation therapy for prostate cancer?

Research shows that using Bicalutamide (Casodex) 150 mg daily as an immediate treatment after radiotherapy significantly reduces the risk of prostate cancer progression by 37% compared to radiotherapy alone, indicating its effectiveness as an adjuvant therapy. ^{1 2 3 4 5}

Is hormone therapy with bicalutamide safe for prostate cancer treatment?

Bicalutamide, used in prostate cancer treatment, is generally well tolerated, but common side effects include breast pain and gynecomastia (enlarged breast tissue in men). In a study, adverse reactions occurred in about 61-65% of patients, but the treatment was still considered safe and effective. ^{2 4 6 7 8}

How does the drug combination of hormone therapy and radiation differ from other prostate cancer treatments?

This treatment combines hormone therapy with radiation, using drugs like bicalutamide (Casodex) to improve survival in high-risk prostate cancer patients. Unlike traditional castration therapies, bicalutamide offers a non-castration-based approach, potentially improving quality of life while effectively enhancing the effects of radiation therapy. ^{2 4 5 9 10}

Research Team

Neil B Desai

Principal Investigator

NRG Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Bicalutamide (Hormone Therapy)
• Buserelin (Hormone Therapy)
• Darolutamide (Drug)
• Degarelix (Hormone Therapy)
• Flutamide (Hormone Therapy)
• Goserelin (Hormone Therapy)
• Histrelin (Hormone Therapy)
• Leuprolide (Hormone Therapy)
• Radiation Therapy (Radiation)
• Relugolix (Hormone Therapy)
• Triptorelin (Hormone Therapy)

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.

Participant Groups

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 Japan, Canada for the following indications:

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+

Findings from Research

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]

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 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]

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 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]

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]

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 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 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]

References

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

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

2. Switzerland 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. [2019]

3. United States 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. [2019]

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

Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells. [2014]

5. Greece 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. [2014]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer]. [2015]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Japan pubmed.ncbi.nlm.nih.gov

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

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

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

10. England 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. [2023]