Hormone Therapy + Radiation for Prostate Cancer

(PCS III Trial)

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Abdenour Nabid

Must be taking: Hormonal therapy

Disqualifiers: Severe psychiatric problems, Chronic hepatic disease, others

Stay on Your Current Meds You can continue your current medications while participating

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 tests whether combining hormone therapy with radiation can more effectively treat prostate cancer by reducing local relapse. Participants will receive either hormone therapy (androgen blockade) with lower or higher doses of radiation, or a higher dose of radiation alone. The goal is to determine if hormone therapy allows for lower radiation doses, potentially leading to fewer side effects. The trial seeks men with early-stage prostate cancer who have not received prior treatment and meet specific health criteria, such as a certain PSA level (a protein produced by the prostate) and no signs of cancer spread. 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 information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that combining hormone therapy with radiation is generally safe for prostate cancer patients. One study found that long-term hormone therapy with radiation increased survival rates without major safety issues. Similarly, 76 Gy radiation proved safe, with a good five-year survival rate.

Another study demonstrated that hormone therapy combined with 76 Gy radiation did not cause unexpected major side effects. However, some patients reported issues like sexual problems, which are common in prostate cancer treatments.

Overall, studies indicate that both treatment methods have been well-tolerated by patients, with no serious safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they explore different combinations of hormone therapy and radiation to optimize outcomes. Androgen blockade, a hormone therapy that reduces male hormones fueling cancer growth, is combined with two different doses of radiotherapy (70 Gy and 76 Gy) to see which combination works best. While the standard treatment often involves either hormone therapy or radiation alone, this trial investigates the potential benefits of synergizing the two. By comparing these combinations with higher-dose radiation alone, researchers aim to discover more effective ways to manage prostate cancer and potentially improve survival rates.

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

This trial will compare different treatment combinations for prostate cancer. Studies have shown that combining hormone-blocking treatment with radiotherapy can be effective. Participants may receive hormone blockers with 70 Gy radiotherapy, which has demonstrated a 5-year survival rate as high as 98.7% for prostate cancer, suggesting a strong potential for improving survival rates. Another group will receive hormone blockers with 76 Gy radiotherapy. Research indicates that higher doses of radiotherapy, along with hormone-blocking treatment, can significantly reduce deaths from prostate cancer. Adding hormone blockers to this higher dose of radiotherapy has been linked to better overall survival outcomes. These findings highlight the promise of these treatment combinations for effectively managing prostate cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

Abdenour Nabid, MD

Principal Investigator

CRC - CHUS

Are You a Good Fit for This Trial?

Men with intermediate-risk prostate cancer, specifically untreated stage T1 or T2 adenocarcinoma of the prostate. Participants must have a Gleason score ≤7 and PSA levels within certain ranges. They should be disease-free from other cancers for over five years, able to attend treatments and follow-ups, and not have severe liver issues or medical/psychiatric conditions that could affect compliance.

Inclusion Criteria

If you had cancer in the past, you can participate if you have been cancer-free for at least five years.

Patients with stage T1 or T2 untreated adenocarcinoma of the prostate, with a Gleason score that is less than or equal to 6, as well as a prostate-specific antigen (PSA) between 10-20 (intermediate risk) or patients with stage T1 or T2 untreated adenocarcinoma of the prostate, with a Gleason score that is equal to 7, as well as a PSA equal to or less than 20 (intermediate risk).

Patients must sign a consent form before starting the study.

Exclusion Criteria

Chronic hepatic disease; abnormal hepatic function, i.e. aspartate aminotransferase and alanine aminotransferase > 1.5 times the upper normal limit.

You have severe medical or mental health issues that may make it difficult for you to follow the study requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Hormonal Therapy

Participants receive neoadjuvant hormonal therapy for four months

16 weeks

Concomitant Hormonal Therapy with Radiation

Participants receive concomitant hormonal therapy for two months with irradiation

8 weeks

Radiation Therapy

Participants receive prostate radiation therapy at either 70 Gy or 76 Gy

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Blockade
• Radiotherapy 70 Gy
• Radiotherapy 76 Gy

Trial Overview The study is testing if six months of hormonal therapy (androgen blockade) can improve outcomes when combined with radiation therapy at two different doses (70 Gy and 76 Gy). It aims to see if hormonal treatment can reduce local failure rates like increasing radiation dose does, potentially offering more treatment options.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 2 Interventions

Androgen blockade for 6 months + Radiotherapy 76 Gy

Group II: Arm 1 Experimental Treatment 2 Interventions

Androgen blockade for 6 months + Radiotherapy 70 Gy

Group III: Arm 3 Active Control 1 Intervention

Radiotherapy alone with 76 Gy

Who Is Running the Clinical Trial?

Abdenour Nabid

Lead Sponsor

Trials

1

Recruited

600+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Combining androgen suppression therapy with external-beam radiation therapy has become the standard treatment for men with locally advanced prostate cancer, significantly improving outcomes such as disease control and survival rates.

Hormonal therapy should be started before radiation and continued throughout the treatment, with recent studies showing that shorter courses of hormone therapy (4 to 6 months) can be effective, challenging the previous belief that longer courses were always necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy combined with hormone therapy for prostate cancer. Lee, AK.[2007]

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 37 men with intermediate- or high-risk localized prostate cancer, a combination of 6 months of androgen-deprivation therapy (ADT) with abiraterone acetate and radiation therapy resulted in a 55% rate of undetectable prostate-specific antigen (PSA) levels at 12 months, indicating effective disease control.

The treatment was associated with manageable toxicity, primarily grade 3 hypertension in 32% of patients, and 81% of participants experienced testosterone recovery within a median time of 9.2 months, suggesting a favorable impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Radiation Therapy and Short-Term Androgen Blockade With Abiraterone Acetate Plus Prednisone for Men With High- and Intermediate-Risk Localized Prostate Cancer. Koontz, BF., Hoffman, KE., Halabi, S., et al.[2021]

In a study of 98 hypogonadal men with prostate cancer treated with radiation therapy, testosterone therapy led to a significant increase in serum testosterone levels, from a median of 209 ng/dl to 420 ng/dl, indicating effective treatment.

The therapy was associated with only a minor increase in prostate specific antigen (PSA) levels and a low rate of biochemical recurrence (6.1%), suggesting that testosterone therapy may be safe for men post-radiation treatment for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. Pastuszak, AW., Khanna, A., Badhiwala, N., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11756135/

Hypofractionated image-guided radiotherapy with 70 Gy in ... For intermediate- to high-risk localized prostate cancer patients, the 5-year overall survival rate was 93.7%, while the 5-year biochemical ...

2. 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 ...

3. 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.

4. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-prostate-cancer/149339-asco-gu-2024-long-term-results-of-dose-escalation-80-vs-70-gy-combined-with-long-term-androgen-deprivation-in-high-risk-prostate-cancer-getug-afu-18-randomized-trial.html

GETUG-AFU 18 Randomized Trial The 5-year prostate cancer specific survival rate was 98.7% (95% CI, 96.2-99.6%) and 96.6% (95% CI, 93.3-98.3%), and the 10-year rate was 95.6% ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9887024/

Androgen deprivation therapy and radiotherapy in ... Androgen deprivation therapy combined with radiotherapy did not show some advantages in terms of overall survival and biochemical recurrence-free survival.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6000067/

Outcomes and toxicity from a prospective study of ... Our results show that moderate hypofractionation with 64 Gy in 20 fractions is feasible and safe in patients with low- to intermediate-risk prostate cancer.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214122

Fifteen-Year Outcomes after Monitoring, Surgery, or ... After median follow-up of 15 years, 45 patients (2.7%) had died of prostate cancer: 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the ...