Radiation + Androgen-Deprivation Therapy for Prostate Cancer

Recruiting at 517 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Radiation Therapy Oncology Group

Must not be taking: LHRH agonists, Antiandrogens, Estrogens, others

Disqualifiers: Gleason score ≥ 8, PSA > 20, Prior 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

1538 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells. Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective with or without androgen-deprivation therapy in treating patients with prostate cancer. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with androgen-deprivation therapy in treating patients with prostate cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used finasteride within 30 days or dutasteride within 90 days before joining the trial.

What data supports the effectiveness of the treatment Radiation + Androgen-Deprivation Therapy for Prostate Cancer?

Research shows that combining radiotherapy with hormone therapy, such as LHRH analogs and antiandrogens, improves survival rates and reduces the risk of cancer returning or spreading in patients with locally advanced prostate cancer. ^{1 2 3 4 5}

Is the combination of radiation and androgen-deprivation therapy safe for prostate cancer patients?

Research shows that using intensity-modulated radiotherapy (IMRT) with androgen deprivation therapy can reduce gastrointestinal side effects compared to three-dimensional conformal radiotherapy (3D-CRT). Additionally, a study found that combining docetaxel with 3D-CRT was safe and well tolerated in high-risk prostate cancer patients. ^{5 6 7 8 9}

What makes the Radiation + Androgen-Deprivation Therapy treatment for prostate cancer unique?

This treatment combines advanced radiation techniques like Intensity-Modulated Radiation Therapy (IMRT), which reduces side effects by targeting cancer more precisely, with androgen-deprivation therapy (hormone therapy that lowers male hormones) to enhance effectiveness, especially in high-risk prostate cancer patients. ^{5 6 10 11 12}

Research Team

Alvaro A. Martinez, MD, FACR

Principal Investigator

21st Century Oncology - Michigan Institute for Radiation Oncology

Eligibility Criteria

Men aged 18+ with intermediate-risk prostate cancer, characterized by specific Gleason scores, PSA levels, and clinical stages. Participants must have no severe co-morbidities or prior treatments like radical surgery for prostate cancer. They should not have used certain medications recently and must be free of other cancers for at least 5 years.

Inclusion Criteria

My prostate cancer has a Gleason score of 7.

My prostate cancer is at an intermediate risk of coming back, based on recent tests.

Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria

More than half of my biopsy samples show cancer, making me ineligible.

I have not taken dutasteride in the last 90 days.

I am HIV positive but do not have AIDS.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen-Deprivation Therapy

Participants receive androgen-deprivation therapy starting 8 weeks prior to radiation therapy

6 months

Radiation Therapy

Participants receive dose-escalated radiation therapy with or without androgen-deprivation therapy

9-17 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 3 months for a year, every 4 months for 4 years, then yearly

Treatment Details

Interventions

• 3-Dimensional Conformal Radiation Therapy
• bicalutamide
• buserelin
• Dose-Escalated Radiation Therapy
• flutamide
• goserelin acetate
• Intensity-Modulated Radiation Therapy
• leuprolide acetate
• triptorelin

Trial Overview This phase III trial is testing the effectiveness of radiation therapy alone versus in combination with androgen-deprivation therapy (ADT) in men with prostate cancer. ADT aims to reduce male hormones that can promote tumor growth.

Participant Groups

Group I: Dose-Escalated Radiation Therapy and Short-Term Androgen-Deprivation Experimental Treatment 4 Interventions

Radiation therapy consists of 79.2 Gy EBRT only or 45 Gy EBRT followed by low- or high-dose rate brachytherapy. EBRT is delivered in 1.8 Gy daily fractions. Six months of androgen-deprivation therapy starts 8 weeks prior to start of radiation therapy and consists of luteinizing-hormone releasing-hormone (LHRH) agonist (antagonist) therapy (leuprolide, goserelin, buserelin. triptorelin, or degarelix) and anti-androgen therapy (bicalutamide or flutamide).

Group II: Dose-Escalated Radiation Therapy Alone Active Control 1 Intervention

Radiation therapy consists of 79.2 Gy EBRT only or 45 Gy EBRT followed by low- or high-dose rate brachytherapy. EBRT is delivered in 1.8 Gy daily fractions.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Who Is Running the Clinical Trial?

Radiation Therapy Oncology Group

Lead Sponsor

Trials

191

Recruited

64,900+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a retrospective study of patients with locally advanced prostate cancer, treatment with radiotherapy (RT) plus LHRH analog triptorelin (monotherapy) showed similar overall survival rates compared to RT plus total androgen block (TAB).

While there was no significant difference in late gastrointestinal and genitourinary toxicities between the two treatment groups, a trend suggested that TAB might offer better progression-free survival, highlighting the importance of considering treatment options that minimize adverse events and maintain quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus Total Androgen Block Versus Radiotherapy Plus LHRH Analog Monotherapy for Non-metastatic Prostate Cancer. Marvaso, G., Viola, A., Fodor, C., et al.[2018]

In three clinical trials for locally advanced prostate cancer, combining external irradiation with LHRH analogues significantly improved various survival rates, including disease-free and overall survival, with a notable P-value of < 0.001.

The EORTC trial 22863 specifically demonstrated a significant overall survival benefit when using the LHRH analogue goserelin acetate from the start of irradiation for three years, while the RTOG trial 85-31 showed survival improvements in patients with poorly differentiated tumors when the LHRH analogue was started during the last week of irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current studies of combined radiotherapy-hormone therapy in localized and locally advanced prostatic cancers]. Bolla, M., Artignan, X., Chirpaz, E., et al.[2019]

In a study of 553 prostate cancer patients, intensity-modulated radiation therapy (IMRT) showed significantly better cancer control compared to three-dimensional conformal radiotherapy (3D-CRT) for intermediate- and high-risk patients, with higher rates of biochemical failure-free survival.

Both treatment methods had similar levels of genitourinary toxicity, but IMRT resulted in lower gastrointestinal toxicity compared to higher doses of 3D-CRT, indicating that IMRT can provide effective treatment without increasing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer. Dolezel, M., Odrazka, K., Zouhar, M., et al.[2022]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus Total Androgen Block Versus Radiotherapy Plus LHRH Analog Monotherapy for Non-metastatic Prostate Cancer. [2018]

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

Comparison of goserelin and leuprolide in combined androgen blockade therapy. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Analysis of testosterone suppression in men receiving histrelin, a novel GnRH agonist for the treatment of prostate cancer. [2013]

4. France pubmed.ncbi.nlm.nih.gov

[Current studies of combined radiotherapy-hormone therapy in localized and locally advanced prostatic cancers]. [2019]

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

The external radiotherapy with three-dimensional conformal boost after the neoadjuvant androgen suppression for patients with locally advanced prostatic carcinoma. [2022]

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

Intensity-modulated radiotherapy reduces gastrointestinal toxicity in patients treated with androgen deprivation therapy for prostate cancer. [2022]

7. 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]

8. Germany pubmed.ncbi.nlm.nih.gov

Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer. [2022]

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

A new paradigm for the treatment of high-risk prostate cancer: radiosensitization with docetaxel. [2023]

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

Does short-term androgen deprivation substitute for radiation dose in the treatment of high-risk prostate cancer? [2019]

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

Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study. [2006]

12. England pubmed.ncbi.nlm.nih.gov

Dose escalation with three-dimensional conformal radiotherapy for prostate cancer. Is more dose really better in high-risk patients treated with androgen deprivation? [2019]