Radiation Therapy + Androgen Deprivation for Prostate Cancer

Not currently recruiting at 474 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must not be taking: Finasteride, Dutasteride, Chemotherapy, others

Disqualifiers: Metastases, Invasive 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: 4-6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to improve treatment for prostate cancer that shows signs of returning after surgery. It compares different combinations of radiation therapy and hormone therapy to determine which most effectively stops cancer growth. Men who have undergone surgery for prostate cancer and now have a rising PSA (a blood test indicating cancer activity) may be suitable candidates. The study tests three approaches: radiation to the pelvic lymph nodes and prostate bed with hormone therapy (including androgen deprivation therapy), radiation to just the prostate bed with hormone therapy, or radiation to just the prostate bed alone. 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 does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy, it must be stopped within 3 months after prostatectomy. Please consult with the trial coordinators for more details.

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

Research has shown that pelvic lymph node radiation therapy is generally safe, with studies confirming a low risk of serious side effects to the urinary and digestive systems. Prostate radiation therapy has produced promising results, although some patients experienced urinary issues during the first two years. For those receiving hormone therapy to lower testosterone levels, common side effects include heart-related risks and changes in sexual health. However, these treatments have improved survival rates and effectively manage prostate cancer. Overall, these treatments are well-tolerated, with generally manageable risks. ^{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 radiation therapy with androgen deprivation therapy (ADT) in innovative ways. Unlike the standard approach that often involves just prostate bed radiation (PBRT), one treatment arm adds pelvic lymph node radiation (PLNRT), potentially targeting cancer cells more comprehensively. Both experimental treatments also utilize short-term androgen deprivation therapy (STAD), which includes antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonists, to suppress hormones that fuel cancer growth. This combination of targeted radiation with hormone-blocking therapy could offer more effective cancer control than current options.

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

Research shows that combining radiation therapy with hormone therapy, known as androgen deprivation therapy (ADT), can lead to better outcomes for prostate cancer patients. In this trial, participants may receive different treatment combinations. One arm involves prostate bed radiotherapy (PBRT) alone. Another arm combines PBRT with short-term ADT (STAD), which includes antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy. A third arm adds pelvic lymph node radiotherapy (PLNRT) to the PBRT and STAD combination. Studies have found that adding ADT to radiation treatment of the prostate area can increase survival rates and lower the chance of cancer spreading. Specifically, short-term ADT has improved overall survival and outcomes related to prostate health. For radiation targeting the pelvic lymph nodes, research found that combining radiation with ADT significantly improved the time patients lived without cancer spreading by 8.6% and overall survival by 7.7%. These findings suggest that using both radiation and hormone therapy together can be more effective than using radiation alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Alan Pollack, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Men aged 18+ who've had prostate surgery for adenocarcinoma of the prostate with no lymph node involvement or unknown status, a PSA level between 0.1 and <2.0 ng/mL post-surgery, and a Gleason score ≤9. They must not have distant metastases, prior pelvic radiotherapy, other recent cancers except certain skin cancers, severe co-morbidities like heart failure or inflammatory bowel disease, HIV/AIDS, or previous allergic reactions to study drugs.

Inclusion Criteria

My cancer has not spread to distant parts of my body.

My prostate cancer was treated with surgery and either no lymph nodes were affected or their status is unknown.

One of the following pathologic classifications: T3N0/Nx disease with or without a positive prostatectomy surgical margin; or T2N0/Nx disease with or without a positive prostatectomy surgical margin; Prostatectomy Gleason score of 9 or less; Zubrod Performance Status of 0-1; Age ≥ 18

Exclusion Criteria

I have a lump in the prostate area that might indicate cancer has returned.

I received chemotherapy before or after my prostate surgery.

I have not had certain cancer treatments like cryosurgery or radiation in the pelvic area recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive prostate bed radiotherapy (PBRT) with or without pelvic lymph node radiotherapy (PLNRT) and short-term androgen deprivation therapy (STAD)

4-6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

3, 6, and 12 months after completion of radiation therapy, then every 6 months for 6 years, and annually thereafter

What Are the Treatments Tested in This Trial?

Interventions

• AA
• LHRH agonist
• Pelvic Lymph Node Radiation Therapy
• Prostate Radiation Therapy

Trial Overview This phase III trial is testing whether radiation therapy alone is as effective as combining it with short-term hormone therapy in treating men whose PSA levels are rising after prostate cancer surgery. It compares pelvic lymph node radiation with/without prostate radiation against androgen deprivation therapy plus pelvic lymph node radiation.

How Is the Trial Designed?

Group I: PLNRT + PBRT + STADT Experimental Treatment 4 Interventions

Pelvic lymph node radiotherapy (PLNRT), prostate bed radiotherapy (PBRT), and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before RT, and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).

Group II: PBRT + STAD Experimental Treatment 3 Interventions

Prostate bed radiotherapy (PBRT) and short term androgen deprivation therapy (STAD) consisting of antiandrogen (AA) and luteinizing hormone-releasing hormone (LHRH) agonist therapy begins within 6 weeks (+/- 2 weeks) after registration. STAD starts first, 2 months (+/- 2 weeks) before radiotherapy (RT), and lasts for 4-6 months. LHRH can last 4-6 months. AA starts at the same time as LHRH (or up to 2 weeks prior ), lasts approximately 4 months, and should end on the last day of RT (+/- 2 weeks).

Group III: PBRT Alone Active Control 1 Intervention

Prostate bed radiotherapy (PBRT) begins within 6 weeks (+/- 2 weeks) after registration.

Who Is Running the Clinical Trial?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Cancer and Leukemia Group B

Collaborator

Trials

81

Recruited

118,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10134326/

Ten‐year outcomes of whole‐pelvic intensity‐modulated ... The reported failure‐free survival rates at 2 years were 81% and 53%, respectively, in the ADT + RT and ADT‐alone groups, and the adjusted ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2287888225000054

Pelvic lymph node management in prostate cancer A MARCAP consortium meta-analysis demonstrated improvement in MFS (metastasis-free survival) 8.6% and OS 7.7% with the addition of any ADT duration, and it is ...

3. redjournal.org redjournal.org/article/S0360-3016(23)08012-4/fulltext

Pelvic Irradiation for Node-Positive Prostate Cancer After ... Pelvic lymph node radiation therapy as field abutment after prostate bed radiation therapy is feasible with long-term survival and no high ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8638529/

Long-Term Outcomes of Dose-Escalated Pelvic Lymph ... The prostate cancer specific survival was 95.2%, and mean prostate cancer specific survival was 8.7 years (95% CI, 8.0-9.4). Five-year distant metastases free ...

5. academic.oup.com academic.oup.com/bjro/article/5/1/20220030/7468230

Outcomes following external beam radiotherapy to the ... 5-year overall survival and prostate cancer-specific survival were 74.4 and 89.1% respectively. 5-year failure-free survival was 55.4%; with 5-year biochemical ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38164028/

Comparison of Short-Term Outcomes and Safety Profiles ... This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4094624/

Androgen deprivation therapy for prostate cancer: long-term ... ADT can normalize serum prostate specific antigen in over 90% of patients and results in sizable tumor response in 80% to 90%. This treatment can be done either ...

8. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/view/42825

Adverse health outcomes for prostate cancer patients ... Overall, 43% (PCa patients) and 20% (controls) reported major sexual problems. In patients aged < 75 years, longer than short ADT duration ...

9. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Treatment advances including ADT have led to improvements in PCa management and survival, with trials reporting median survival of over 6 years ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124000282

A 3-year Interim Analysis of the Observational J-ROCK Study In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone- ...