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

630 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to use as a reference the 36-month duration of hormonal therapy according to the European Organization for Research of the Treatment of Cancer (EORTC protocol 22863) : namely one-month of total androgen blockade followed by a luteinizing hormone releasing hormone (LHRH) agonist, all for three years, combined with pelvic and prostate irradiation; this arm is currently considered to be a standard for high-risk prostate cancers. The proposed study intends to challenge the duration of hormonal therapy and verify whether the five-year outcomes in favour of combined treatment in regard to survival (79% versus 62%) and local control (85% versus 48%) can be transposed for hormonal therapy that is half as long, namely 18 months, with the possibility of hormone salvage therapy in the event of biochemical and/or clinical failure (local, regional, or distant); this applies to both arms. The proposed study will compare survival in the two groups and evaluate in each one the total duration of initial hormonal therapy, followed by initial hormonal therapy combined with salvage hormonal therapy, the duration of salvage hormonal therapy until hormonal therapy resistance, and the side effects of this hormonal therapy, with everything being related to an assessment of the quality of life of these patients.

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.

What data supports the effectiveness of the treatment Hormone Therapy + Radiation for Prostate Cancer?

Research shows that combining radiotherapy with hormonal therapy can improve local control rates in prostate cancer patients. Techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) allow for higher treatment doses with lower side effects, making them effective options for treating localized prostate cancer. ^{1 2 3 4 5}

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

Research shows that combining hormone therapy with various forms of radiation, like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), is generally safe for treating prostate cancer. These treatments have been shown to reduce side effects and spare normal tissue, with studies reporting decreased acute toxicities and manageable long-term effects. ^{6 7 8 9 10}

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

This treatment combines hormone therapy, which blocks male hormones that fuel prostate cancer, with radiation therapy to target and kill cancer cells. It is unique because it has shown improved outcomes in controlling the disease and increasing survival rates, especially in men with locally advanced or high-risk prostate cancer, compared to using either therapy alone. ^{11 12 13 14 15}

Research Team

Abdenour Nabid, MD

Principal Investigator

Centre de Recherche Clinique Étienne LeBel/CHUS Fleurimont

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Radiotherapy in prostate cancer]. [2021]

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

Beyond Just Androgen Deprivation Therapy: Novel Therapies Combined With Radiation. [2018]

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

[What is the level of evidence of new techniques in prostate cancer radiotherapy?]. [2018]

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

Salvage of locally recurrent prostate cancer after external beam radiation using reduced-dose brachytherapy with neoadjuvant plus adjuvant androgen deprivation. [2022]

5. Ireland 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. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Percutaneous radiotherapy for low-risk prostate cancer: options for 2007. [2018]

7. Japan 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. [2018]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. [2021]

9. Thailand pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy combined with endocrine therapy for intermediate and advanced prostate cancer: long-term outcome of Chinese patients. [2019]

10. United States 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. [2022]

11. 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]

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

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

13. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer. [2022]

14. Greece pubmed.ncbi.nlm.nih.gov

Feasibility of simultaneous integrated boost IMRT (SIB-IMRT) for castration-resistant prostate cancer. [2014]

15. England pubmed.ncbi.nlm.nih.gov

A systematic overview of radiation therapy effects in prostate cancer. [2019]