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

600 Participants Needed

Trial Summary

What is the purpose of this trial?

The hypothesis of the proposed study would be that, due to the six months of total androgen blockade, which would include neoadjuvant hormonal therapy for four months and concomitant hormonal therapy for two months with irradiation, the investigators could reduce local failure rates for these two dosage levels, namely 70 Gy and 76 Gy. Since increasing the dose to the prostate also seems to reduce local relapse rates, the results of the two hormonal therapy groups would be compared with the results of prostate irradiation at doses of 76 Gy. This study would verify the possibility of compensating a six Gy dosage increase of radiation therapy with six months of hormonal therapy between the 70 Gy and 76 Gy groups who received hormonal therapy, and also match these results with a dose escalation to the prostate of 76 Gy. In the future, this could result in more therapeutic choices, such as reducing the doses of radiation therapy and, consequently, its related complications, if hormonal therapy proves to be beneficial; or rather, to continue in the direction of dose escalation for this intermediate-risk patient group, everything being correlated to the side effects of hormonal therapy and irradiation.

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.

What data supports the effectiveness of this treatment for prostate cancer?

Research shows that combining hormone therapy (which blocks male hormones) with radiation can improve survival rates in prostate cancer patients, especially those with higher risk. Studies have found that this combination reduces cancer markers and improves outcomes compared to radiation alone. ^{1 2 3 4 5}

Is hormone therapy combined with radiation safe for prostate cancer treatment?

The combination of hormone therapy and radiation for prostate cancer has been studied, and while it can be effective, it may cause side effects like hypogonadism (reduced hormone production). Safety data suggests that while there are potential toxicities, the treatment is generally considered safe for use in humans. ^{1 2 5 6 7}

How does the treatment of hormone therapy combined with radiation differ from other prostate cancer treatments?

This treatment is unique because it combines hormone therapy, which blocks male hormones that fuel prostate cancer, with radiation therapy to target and kill cancer cells. The combination is particularly effective for locally advanced prostate cancer, improving survival rates compared to using either treatment alone. ^{2 3 8 9 10}

Research Team

Abdenour Nabid, MD

Principal Investigator

CRC - CHUS

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

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

Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. [2019]

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

Short-course androgen ablation combined with external-beam radiation therapy and low-dose-rate permanent brachytherapy in early-stage prostate cancer: a matched subset analysis. [2006]

3. France pubmed.ncbi.nlm.nih.gov

[Combination of external irradiation and androgen suppression for prostate cancer: facts and questions]. [2010]

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

Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy. [2020]

5. Greece pubmed.ncbi.nlm.nih.gov

Dose-escalated radiation therapy with and without short-course androgen deprivation for intermediate-risk prostate cancer. [2014]

6. United States 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. [2021]

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

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. [2016]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Hormone and radiotherapy versus hormone or radiotherapy alone for non-metastatic prostate cancer: a systematic review with meta-analyses. [2022]

10. 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]