Androgen-Deprivation + Radiation Therapy for Prostate Cancer

Not currently recruiting at 549 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining androgen-deprivation therapy (a treatment to reduce male hormones) with radiation therapy effectively treats prostate cancer. Androgens, or male hormones, can promote the growth of prostate cancer cells. The trial will test whether reducing these hormones and using radiation together is more effective than radiation alone. Participants will receive either whole-pelvic radiation or high-dose radiation, possibly with brachytherapy (a type of internal radiation). Men with prostate cancer at moderate to high risk of recurrence, who have not yet undergone surgery or hormone treatments, may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that androgen-deprivation therapy (ADT) is generally well-tolerated by most patients. However, about 43% of prostate cancer patients on ADT experience significant sexual problems, compared to 20% of those not on ADT. Interestingly, patients over 75 years old seem to handle ADT better than younger patients.

Radiation therapy, such as intensity-modulated radiotherapy (IMRT), provides a safe and effective way to treat prostate cancer. This treatment uses precise energy beams to target cancer cells. Some patients might experience urinary or bowel issues, but these are usually manageable, and severe side effects are uncommon.

Overall, both treatments have been widely used and studied for their safety in treating prostate cancer. Patients should discuss any concerns with their healthcare team to understand how these treatments might affect them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of androgen-deprivation therapy and radiation therapy for prostate cancer because it offers a potentially more comprehensive approach than standard treatments. Unlike traditional methods that often focus on either hormone therapy or radiation alone, this approach combines both, targeting the cancer on multiple fronts. The use of whole-pelvic radiotherapy and the option for brachytherapy in one arm allows for a more tailored and potentially more effective treatment, addressing both localized and more widespread cancer areas. This dual approach aims to increase the chances of controlling the cancer while minimizing side effects, which could lead to improved outcomes for patients.

What evidence suggests that androgen-deprivation therapy and radiation therapy could be effective for prostate cancer?

This trial will compare different radiation therapy approaches combined with hormone therapy for prostate cancer. Research has shown that combining hormone therapy, or androgen-deprivation therapy (ADT), with radiation effectively treats prostate cancer. Studies have found that treating the whole pelvic area with radiation, as in one arm of this trial, can improve survival rates, with 86.3% of patients surviving prostate cancer after 10 years. Another arm of this trial involves high-dose radiation treatments, such as brachytherapy, which also show strong results, with an 85% success rate in controlling the cancer. Both treatments aim to stop cancer growth and destroy cancer cells, offering promising outcomes for patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Mack Roach, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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]

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