Radiation + Androgen-Deprivation Therapy for Prostate Cancer

No longer recruiting at 530 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must not be taking: LHRH agonists, Antiandrogens, Estrogens, others

Disqualifiers: Gleason score ≥ 8, PSA > 20, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining radiation therapy with androgen-deprivation therapy (which reduces male hormones that fuel prostate cancer growth) is more effective than radiation therapy alone for treating prostate cancer. The goal is to determine which method better shrinks tumors and prevents cancer recurrence. Men with intermediate-risk prostate cancer, who have not undergone treatments like surgery or certain hormonal therapies, might be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used finasteride within 30 days or dutasteride within 90 days before joining the trial.

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

Research has shown that higher doses of radiation in prostate cancer treatment are generally safe and result in fewer treatment failures. Studies indicate that this approach effectively targets cancer cells and is well-tolerated by patients.

For those combining radiation with hormone therapy, which reduces male hormones that help cancer grow, findings suggest this combination is safe. Although it does not increase overall survival, it improves certain outcomes without causing significant side effects. The treatment includes drugs like bicalutamide and goserelin, which are already approved for prostate cancer, confirming their safety.

Overall, both treatments appear to be safe options for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they aim to enhance the effectiveness of prostate cancer treatment by combining dose-escalated radiation therapy with androgen-deprivation therapy (ADT). Unlike standard treatments that often use one method at a time, this approach integrates high-dose radiation with hormone therapy to potentially shrink tumors more effectively and quickly. The use of advanced radiation techniques like 3-Dimensional Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy allows for precise targeting of cancer cells, possibly leading to better outcomes and fewer side effects. Additionally, the inclusion of various LHRH agonists like leuprolide and goserelin, along with anti-androgens such as bicalutamide, offers a comprehensive attack on cancer by both reducing testosterone levels and blocking its effects.

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

This trial will compare Dose-Escalated Radiation Therapy alone with Dose-Escalated Radiation Therapy combined with Short-Term Androgen-Deprivation Therapy (ADT). Research has shown that radiation therapy effectively destroys prostate cancer cells. Androgen-deprivation therapy (ADT) is often added to reduce male hormones that help cancer grow, aiming to enhance the treatment's effects. However, studies have found that adding short-term ADT to radiation therapy does not significantly increase the overall survival of prostate cancer patients. Some research suggests improvements in certain test results, but no clear survival benefit has been confirmed. Therefore, while radiation therapy is a proven treatment, the added benefit of ADT remains uncertain. ^{1 2 6 7 8}

Who Is on the Research Team?

Alvaro A. Martinez, MD, FACR

Principal Investigator

21st Century Oncology - Michigan Institute for Radiation Oncology

Are You a Good Fit for This Trial?

Men aged 18+ with intermediate-risk prostate cancer, characterized by specific Gleason scores, PSA levels, and clinical stages. Participants must have no severe co-morbidities or prior treatments like radical surgery for prostate cancer. They should not have used certain medications recently and must be free of other cancers for at least 5 years.

Inclusion Criteria

My prostate cancer has a Gleason score of 7.

My prostate cancer is at an intermediate risk of coming back, based on recent tests.

Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria

More than half of my biopsy samples show cancer, making me ineligible.

I have not taken dutasteride in the last 90 days.

I am HIV positive but do not have AIDS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen-Deprivation Therapy

Participants receive androgen-deprivation therapy starting 8 weeks prior to radiation therapy

6 months

Radiation Therapy

Participants receive dose-escalated radiation therapy with or without androgen-deprivation therapy

9-17 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 3 months for a year, every 4 months for 4 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• 3-Dimensional Conformal Radiation Therapy
• bicalutamide
• buserelin
• Dose-Escalated Radiation Therapy
• flutamide
• goserelin acetate
• Intensity-Modulated Radiation Therapy
• leuprolide acetate
• triptorelin

Trial Overview This phase III trial is testing the effectiveness of radiation therapy alone versus in combination with androgen-deprivation therapy (ADT) in men with prostate cancer. ADT aims to reduce male hormones that can promote tumor growth.

How Is the Trial Designed?

Group I: Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation Experimental Treatment 4 Interventions

Radiation therapy consists of 79.2 Gy EBRT only or 45 Gy EBRT followed by low- or high-dose rate brachytherapy. EBRT is delivered in 1.8 Gy daily fractions. Six months of androgen-deprivation therapy starts 8 weeks prior to start of radiation therapy and consists of luteinizing-hormone releasing-hormone (LHRH) agonist (antagonist) therapy (leuprolide, goserelin, buserelin. triptorelin, or degarelix) and anti-androgen therapy (bicalutamide or flutamide).

Group II: Dose-Escalated Radiation Therapy Alone Active Control 1 Intervention

Radiation therapy consists of 79.2 Gy EBRT only or 45 Gy EBRT followed by low- or high-dose rate brachytherapy. EBRT is delivered in 1.8 Gy daily fractions.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

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

In a study of 553 prostate cancer patients, intensity-modulated radiation therapy (IMRT) showed significantly better cancer control compared to three-dimensional conformal radiotherapy (3D-CRT) for intermediate- and high-risk patients, with higher rates of biochemical failure-free survival.

Both treatment methods had similar levels of genitourinary toxicity, but IMRT resulted in lower gastrointestinal toxicity compared to higher doses of 3D-CRT, indicating that IMRT can provide effective treatment without increasing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer. Dolezel, M., Odrazka, K., Zouhar, M., et al.[2022]

In three clinical trials for locally advanced prostate cancer, combining external irradiation with LHRH analogues significantly improved various survival rates, including disease-free and overall survival, with a notable P-value of < 0.001.

The EORTC trial 22863 specifically demonstrated a significant overall survival benefit when using the LHRH analogue goserelin acetate from the start of irradiation for three years, while the RTOG trial 85-31 showed survival improvements in patients with poorly differentiated tumors when the LHRH analogue was started during the last week of irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current studies of combined radiotherapy-hormone therapy in localized and locally advanced prostatic cancers]. Bolla, M., Artignan, X., Chirpaz, E., et al.[2019]

In a retrospective study of patients with locally advanced prostate cancer, treatment with radiotherapy (RT) plus LHRH analog triptorelin (monotherapy) showed similar overall survival rates compared to RT plus total androgen block (TAB).

While there was no significant difference in late gastrointestinal and genitourinary toxicities between the two treatment groups, a trend suggested that TAB might offer better progression-free survival, highlighting the importance of considering treatment options that minimize adverse events and maintain quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus Total Androgen Block Versus Radiotherapy Plus LHRH Analog Monotherapy for Non-metastatic Prostate Cancer. Marvaso, G., Viola, A., Fodor, C., et al.[2018]

Citations

1. redjournal.org redjournal.org/article/S0360-3016(25)06022-5/fulltext

Phase 3 Trial of Dose-Escalated Radiation Therapy and ... The study was designed to evaluate overall survival for 900 men with high-risk prostate cancer (Gleason 9-10, prostate specific antigen (PSA) > ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10489479/

Dose-Escalated Radiotherapy Alone or in Combination With ... Although 6 months of androgen deprivation did not produce an overall survival (OS) advantage, it was associated with improvements in rates of biochemical ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625060225

Phase III trial of dose escalated radiation therapy and ... The addition of orteronel to dose escalated RT and ADT did not result in statistically significant improvement in efficacy outcomes, although ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27191936/

Evaluation of the effectiveness of adding androgen ... Adding ADT to modern dose-escalated RT was not associated with improved survival for patients with favorable intermediate-risk prostate cancer.

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.22.02390

Results of a Phase III Multi-Institutional Trial It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer ...

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

Short-term Androgen Deprivation Therapy and High-dose ... Among the 370 patients in the modified intention-to-treat population, 241 (65%) had intermediate-risk and 107 (28%) high-risk prostate cancer.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.LBA259

Long-term results of dose escalation (80 vs 70 Gy ... Conclusions: Dose-escalation RT in combination with long-term ADT is effective and safe, increasing not only the bcPFS rate but also specific ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.70013

Outcomes show a reduction in treatment failure associated ... Outcomes show a reduction in treatment failure associated with dose-escalated, hypofractionated radiation therapy for localized prostate cancer.