Androgen-Deprivation + Radiation Therapy for Prostate Cancer

Recruiting at 533 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must not be taking: LHRH agonists, Anti-androgens

Disqualifiers: Bladder cancer, AIDS, 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: Unknown

2592 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens. Radiation therapy uses high-energy x-rays to kill tumor cells. PURPOSE: This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like finasteride 30 days before joining and dutasteride 90 days before joining. If you are on hormonal therapy or certain other prostate cancer treatments, you may need to stop those as well. It's best to discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the treatment Androgen-Deprivation + Radiation Therapy for Prostate Cancer?

Research shows that combining androgen deprivation therapy (ADT) with radiation therapy is beneficial for patients with intermediate- and high-risk prostate cancer, improving survival rates and outcomes. ^{1 2 3 4 5}

Is androgen-deprivation therapy combined with radiation therapy generally safe for humans?

Androgen-deprivation therapy (ADT) combined with radiation therapy is generally safe but can have side effects affecting various body systems, including weight gain, loss of libido, hot flashes, and impacts on metabolism, muscles, heart, brain, and sexual health. These side effects are manageable with proper monitoring and care. ^{6 7 8 9 10}

How is the treatment of androgen-deprivation therapy combined with radiation therapy unique for prostate cancer?

This treatment is unique because it combines androgen-deprivation therapy, which reduces male hormones that can fuel prostate cancer growth, with radiation therapy to enhance the effectiveness of the radiation. This combination has been shown to improve survival in intermediate and high-risk prostate cancer patients compared to radiation alone. ^{1 11 12 13 14}

Research Team

Mack Roach, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Men with moderate to high-risk prostate cancer, confirmed by biopsy within the last 180 days. They should have a PSA level under 50 ng/mL and no bone metastases. Men previously on active surveillance for low risk prostate cancer who now have higher risk disease may also join if re-biopsied within 180 days. No prior pelvic radiation or radical prostate surgery is allowed, and they must be willing to use contraception.

Inclusion Criteria

I was diagnosed with prostate cancer at moderate to high risk of coming back within the last 6 months.

ANC ≥ 1,500/mm³

Baseline serum PSA value performed within 120 days prior to registration

Exclusion Criteria

I am not willing or able to use birth control.

I have had radiation to my pelvis, seed implants in my prostate, or both testicles removed.

I have had a condition where my lymphocytes grow abnormally.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Androgen-Deprivation Therapy

Participants receive neoadjuvant androgen-deprivation therapy comprising bicalutamide or flutamide and LHRH agonist/antagonist therapy for 6 months

6 months

Radiotherapy

Participants undergo radiotherapy, either high-dose radiotherapy of the prostate and seminal vesicles or whole-pelvic radiotherapy, for approximately 9 weeks

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year with decreasing frequency

Treatment Details

Interventions

• Androgen-Deprivation Therapy
• Radiation Therapy

Trial Overview This phase III trial is testing whether combining androgen-deprivation therapy (which lowers male hormones) with whole-pelvic radiotherapy (a type of radiation that targets the entire pelvic area) is effective in treating patients with prostate cancer compared to other treatments.

Participant Groups

Group I: Arm II Experimental Treatment 1 Intervention

Patients undergo whole-pelvic radiotherapy (WPRT)\* (3D-CRT or IMRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in arm I.

Group II: Arm I Active Control 1 Intervention

Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT)\* or 3D-conformal radiation therapy (3D-CRT)\* once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy (I 125 or Pd 103 may be used as the radioisotope).

Who Is Running the Clinical Trial?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In intermediate-risk prostate cancer patients (520 participants), androgen deprivation therapy (ADT) significantly improved biochemical relapse-free rates, particularly in those with multiple risk factors, indicating that short-term ADT (≤6 months) is beneficial.

For high-risk prostate cancer patients (555 participants), longer ADT durations (>6 months) were associated with better biochemical relapse-free rates, especially for those with multiple high-risk factors, suggesting that ADT for ≥21 months may be optimal when combined with high-dose proton beam therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. Murakami, M., Ishikawa, H., Shimizu, S., et al.[2020]

In a study of 373 intermediate-risk prostate cancer patients treated with radiotherapy over 14 years, those aged 70 or younger who received radiotherapy alone had a higher risk of biochemical failure compared to those who received combined radiotherapy and androgen deprivation therapy (ADT).

The results suggest that short-term ADT may be beneficial for younger patients with favorable intermediate-risk prostate cancer, as it improved biochemical relapse-free survival from 82.1% to 94.0% compared to radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer? Amit, U., Lawrence, YR., Weiss, I., et al.[2020]

In a study of 18,598 men with favorable intermediate-risk prostate cancer, adding androgen-deprivation therapy (ADT) to modern dose-escalated radiotherapy (RT) did not improve overall survival rates, with 8-year survival at 77.7% for ADT plus RT and 78.4% for RT alone.

The findings suggest that for patients with favorable intermediate-risk prostate cancer, using dose-escalated RT alone may be a reasonable treatment option, as ADT did not show survival benefits and carries potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer. Falchook, AD., Basak, R., Mohiuddin, JJ., et al.[2018]

Androgen deprivation therapy, often used alongside radiotherapy for localized and advanced prostate cancer, can lead to various side effects affecting multiple body systems, including metabolism, muscles, heart health, brain function, and sexual health.

This review emphasizes the importance of monitoring and managing the toxic effects of androgen deprivation therapy to enhance patient care and reduce these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy toxicity and management for men receiving radiation therapy. Johnson, ME., Buyyounouski, MK.[2021]

In a phase II study involving 62 patients with intermediate-risk prostate cancer, enzalutamide monotherapy combined with hypofractionated external beam radiation therapy (Hypo-EBRT) resulted in a greater than 80% decline in PSA levels for all evaluable patients, indicating high efficacy in treatment.

The treatment was generally well-tolerated, with common side effects including hypertension, asthenia, and gynecomastia, but no significant changes in bone density or body mass index were observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer. Lara, PC., Rodríguez-Melcón, JI., Palacios-Eito, A., et al.[2022]

Androgen deprivation therapy (ADT) is commonly used alongside radiotherapy to treat prostate cancer, and understanding the biology of the androgen axis can enhance the effectiveness of these combined treatments.

Recent approvals of new drugs necessitate further pre-clinical and clinical studies to explore their potential benefits when used in conjunction with radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The androgen receptor for the radiation oncologist. Quero, L., Rozet, F., Beuzeboc, P., et al.[2015]

Androgen deprivation therapy (ADT) is a key treatment for prostate cancer, enhancing the effectiveness of local therapies like radiation and providing significant relief for metastatic cases.

While ADT is effective, it can lead to adverse effects such as hot flashes, decreased bone density, metabolic changes, and gynecomastia, which require careful management and ongoing research to address.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of the side effects of androgen deprivation therapy in men with prostate cancer. Flaig, TW., Glodé, LM.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer? [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Androgen Deprivation Therapy Combined With Particle Therapy for Prostate Cancer: A Systematic Review. [2022]

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

Role of androgen deprivation therapy in early salvage radiation among patients with prostate-specific antigen level of 0.5 or less. [2021]

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

Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Initial results of a randomized phase III trial of high dose image guided radiation with or without androgen deprivation therapy for intermediate-risk prostate cancer. [2019]

7. Egypt pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy toxicity and management for men receiving radiation therapy. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Androgen Deprivation Therapy on Prostate Cancer Outcomes According to Competing Event Risk: Secondary Analysis of a Phase 3 Randomised Trial. [2023]

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

Dose-escalated radiation therapy for intermediate-risk prostate cancer: patient selection for androgen deprivation therapy using percentage of positive cores. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A systematic review and meta-analysis. [2023]

12. France pubmed.ncbi.nlm.nih.gov

The androgen receptor for the radiation oncologist. [2015]

13. England pubmed.ncbi.nlm.nih.gov

Management of the side effects of androgen deprivation therapy in men with prostate cancer. [2019]

14. 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]