Hormone Therapy + Radiation for Prostate Cancer

(PCS IV Trial)

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Université de Sherbrooke

Must be taking: Hormonal therapy

Disqualifiers: Severe medical, psychiatric, chronic hepatic, 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 explores whether hormone therapy for prostate cancer, specifically androgen blockade, can be as effective when administered for 18 months instead of the usual 36 months. The study compares two groups: one receiving the standard three-year hormone treatment plus radiation, and another receiving an 18-month hormone treatment with the same radiation. Researchers aim to determine if the shorter treatment is equally effective for survival and quality of life. Men with high-risk prostate cancer, indicated by factors like advanced tumor classification or high PSA levels, might be suitable candidates for this trial. 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 information does not specify if you need to stop taking your current medications. However, hormonal therapy is allowed up to two months before joining the study, so you may be able to continue some treatments. It's best to discuss your specific medications with the trial team.

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

Research has shown that using medications like bicalutamide and goserelin together, known as combined androgen blockade, is generally safe for treating prostate cancer. Studies have found that this combination can extend patients' lives without major safety concerns. Most patients tolerate these treatments well, rarely experiencing severe side effects.

Research confirms that radiation therapy is generally safe and effective for prostate cancer. Some patients might experience mild urinary problems, but these are neither serious nor long-lasting. Overall, radiation therapy is well-tolerated, with only minor side effects.

Both combined androgen blockade and radiation therapy have been widely used in treating prostate cancer and are known for their safety. These factors make them promising options for patients considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of hormone therapy and radiation for prostate cancer because it offers a potentially more effective approach compared to traditional hormone therapy alone. Unlike standard treatments, which usually involve shorter hormone therapy durations, this study explores the effects of extending androgen blockade to either 18 or 36 months. The longer hormone therapy period, combined with radiation, might improve outcomes by more effectively reducing testosterone levels, which prostate cancer cells need to grow. Additionally, this approach could lead to better long-term control of cancer progression, making it a promising option for patients.

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

This trial will compare two durations of hormone therapy combined with radiation treatment for prostate cancer. Studies have shown that combining hormone therapy with radiation treatment effectively treats prostate cancer. Specifically, patients receiving both treatments have a 5-year survival rate of 75.3%, compared to 63.4% for those using only hormone therapy. This combination also reduces the risk of death by 20% compared to hormone therapy alone. Radiation treatment is a proven method for controlling prostate cancer that hasn't spread, offering long-term disease management. These findings support the potential effectiveness of combining these therapies for improved outcomes in prostate cancer treatment. ^{2 4 6 7 8}

Who Is on the Research Team?

Abdenour Nabid, MD

Principal Investigator

Centre de Recherche Clinique Étienne LeBel/CHUS Fleurimont

Are You a Good Fit for This Trial?

Men with high-risk prostate cancer who have a tumor classified as T3 or T4, Gleason score of 8-10, or PSA level >20. They must be in good physical condition (performance status 0-1), without distant metastasis or regional disease, and no progression of any previous cancers for over five years. Participants can have had up to two months of hormonal therapy before joining.

Inclusion Criteria

No distant metastasis. These patients must all have a negative bone scan 12 weeks prior to randomization

To have at least one of the following three risk factors: Tumour classified T3 or T4

Gleason score 8-10

Exclusion Criteria

Severe medical or psychiatric problems that could compromise study compliance

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Hormonal Therapy

Participants receive one month of total androgen blockade followed by a luteinizing hormone releasing hormone (LHRH) agonist

36 months or 18 months depending on the arm

Radiation Therapy

Participants receive pelvic and prostate irradiation

Concurrent with hormonal therapy

Follow-up

Participants are monitored for survival, local control, and quality of life

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Blockade
• Radiation Therapy

Trial Overview The trial is testing if an 18-month course of androgen blockade combined with pelvic irradiation is as effective as the standard three-year treatment for improving survival rates in high-risk prostate cancer patients. It will also assess quality of life and side effects related to the duration of hormone therapies.

How Is the Trial Designed?

Group I: Arm 2 : 18 months AB + RT Experimental Treatment 1 Intervention

Androgen blockade 18 months : bicalutamide 50 mg die for one month, goserelin 10.8 mg x 6 Q 3 months + radiation therapy ( pelvis 44 grays , prostate 70 grays ,2 grays/fraction)

Group II: Arm 1 : 36 months AB + RT Active Control 1 Intervention

Androgen blockade : 36 months of androgen blockade : bicalutamide 50 mg die for one month, goserelin 10.8 mg x 12 Q 3 months + radiation therapy : pelvis 44 grays , prostate 70 grays (2 grays/fraction)

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

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

Intensity-modulated radiation therapy (IMRT) resulted in significantly lower rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity compared to (125)I seed implants, with 3-year rates of 3.5% GU and 2.4% GI toxicity for IMRT versus 19.2% GU and 7.7% GI for (125)I.

Both treatments showed similar biochemical failure rates, with IMRT having a 4-year freedom from failure rate of 99.5% compared to 93.5% for (125)I, indicating that while both are effective, IMRT may be safer with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Eade, TN., Horwitz, EM., Ruth, K., et al.[2022]

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 a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

In a study of 260 men with localized prostate cancer treated with high-dose IGRT and IMRT, the combination resulted in a low rate of late toxicity, with only 4.4% experiencing grade 2 gastrointestinal issues and 7.1% with grade 2 genitourinary issues after 7 years.

The treatment showed high efficacy, with a 7-year prostate-specific antigen relapse-free survival rate of 97.1% for low-risk patients, indicating that this approach is both safe and effective for managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. Doležel, M., Odrážka, K., Vaňásek, J., et al.[2021]

A systematic review of 40 studies found that combining external beam radiotherapy (EBRT) with high-dose rate (HDR) brachytherapy (EBTI) provides superior biochemical control and overall survival for prostate cancer patients.

Specifically, the risk of biochemical recurrence and overall survival was significantly better with EBTI compared to EBRT and EBSeeds, with hazard ratios indicating a 40% and 50% increased risk of recurrence and mortality, respectively, for EBRT compared to EBTI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: a systematic review. Pieters, BR., de Back, DZ., Koning, CC., et al.[2018]

Radiotherapy is as effective as radical prostatectomy for localized prostate cancer when administered at sufficient doses, with various modalities like interstitial brachytherapy and external beam radiotherapy available.

Advancements such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) allow for higher radiation doses while reducing toxicity, and combining radiotherapy with hormonal ablation enhances local control rates in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy in prostate cancer]. Ganswindt, U., Belka, C.[2021]

Prostate cancer treatment has advanced significantly from traditional 2D radiotherapy to more precise methods like intensity-modulated radiation therapy (IMRT) and stereotactic radiotherapy, enhancing treatment efficacy and reducing side effects.

Emerging techniques such as proton therapy and carbon therapy are being explored to further improve treatment outcomes, shorten treatment times, and minimize toxicity and costs for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What is the level of evidence of new techniques in prostate cancer radiotherapy?]. Khadige, M., Peiffert, D., Supiot, S.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6198209/

Combined androgen blockade achieved better oncological ... The CAB group showed a significantly better progression‐free survival (PFS) rate (65.6% vs 59.6% at 5 years; median time to progression, 11.6 vs 7.1 years; ...

2. nature.com nature.com/articles/s41392-024-02064-z

Patient-reported outcomes of rezvilutamide versus ... REZ-ADT is superior to BIC-ADT regarding the pain alleviation and enhancement of functional scales for high-volume mHSPC.

3. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.24395

Combined androgen blockade with bicalutamide for advanced ... The 5-year overall survival rate estimated by the Kaplan-Meier method was 75.3% for CAB versus 63.4% for LHRH-A monotherapy. The results from ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3735079/

Use of androgen deprivation therapy in prostate cancer Patients randomized to the combination arm had a significantly higher survival (P=0.04), lower prostate cancer-specific mortality (P=0.02) and higher survival ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1558767311701008

Combined Androgen Blockade in Advanced Prostate Cancer This analysis showed that combined androgen blockade with bicalutamide was associated with a 20% reduction in the risk of death compared with castration alone.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21091846/

Combined androgen blockade for prostate cancer CAB using this new antiandrogen was found to prolong overall survival (OS) in patients with prostate cancer, with favorable safety profiles and cost- ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5048

Patient-reported outcomes (PROs) for rezvilutamide versus ... The 25th percentile for the time to average pain progression was 25.8 months (95% CI 14.8–31.4) in the rezvilutamide plus ADT group and 11.7 ...

8. 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- ...