Hormone + Radiation Therapy for Metastatic Prostate Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: Anti-hormone therapy

Disqualifiers: Brain metastases, Orchiectomy, Unstable conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining hormone therapy with specialized radiation can effectively treat prostate cancer that has spread. Hormone therapy reduces androgens, which aid cancer cell growth, using medications like goserelin (Goserelin Acetate), leuprolide (Leuprolide Acetate), or bicalutamide. Radiation therapy targets tumors with high-energy x-rays to kill cancer cells while sparing healthy tissue. The trial seeks participants with prostate cancer that has spread and who have not received radiation or chemotherapy for this condition, although previous non-chemotherapy treatments may be acceptable. This trial may suit those who have experienced cancer spread but remain sensitive to hormone treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you can continue using bisphosphonates if your doctor agrees. 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?

In a previous study, bicalutamide, a hormone therapy, was well-tolerated by men with prostate cancer. Another study showed that bicalutamide is generally safe, with manageable side effects.

Goserelin acetate, another hormone therapy used in the trial, has been shown by research to be well-tolerated, with common side effects like mild hot flashes and pain.

Leuprolide acetate, also used in hormone therapy, has a well-known safety record. Most doctors rate its safety and tolerability as good or excellent. However, there is a small risk of heart-related issues, so discussing this with a doctor is important.

For radiation therapy, intensity-modulated radiation therapy (IMRT) has been studied for safety. One study found no severe side effects, suggesting it is a safe treatment option. Some patients might experience mild urinary issues.

Overall, these treatments are generally well-tolerated based on past research, but discussing potential side effects with a healthcare provider is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for metastatic prostate cancer because it combines hormone therapy with a precise form of radiation called Intensity-Modulated Radiation Therapy (IMRT). Unlike other treatments that might use more generalized radiation methods, IMRT allows for targeted radiation that minimizes damage to surrounding healthy tissue. Additionally, the combination of hormone therapies, including bicalutamide, goserelin acetate, and leuprolide acetate, aims to aggressively reduce androgen levels, which can help slow down the growth of prostate cancer cells. This dual approach has the potential to improve outcomes by both shrinking tumors and limiting the cancer's ability to spread.

What evidence suggests that hormone and radiation therapy might be an effective treatment for metastatic prostate cancer?

This trial will evaluate the combination of hormone therapy and intensity-modulated radiation therapy (IMRT) for treating metastatic prostate cancer. Participants may receive Bicalutamide, which research has shown can lower the risk of cancer progression by 42% when combined with standard care. Goserelin acetate, another treatment option in this trial, helps maintain low testosterone levels, slowing cancer growth. Similarly, Leuprolide acetate reduces testosterone to help control prostate cancer. IMRT, part of the treatment regimen, has proven very effective, keeping cancer under control in 99% of cases over the long term. These treatments work together to target cancer cells more precisely and slow their growth. ^{1 6 7 8 9}

Who Is on the Research Team?

Cy A Stein

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for men with metastatic prostate cancer who haven't had prior radiation for metastasis, have a good performance status (WHO 0-2), and have limited number of lesions. They should not have brain metastases or severe medical conditions, no history of orchiectomy, and must not be refractory to hormone therapy.

Inclusion Criteria

I may have had hormone therapy for up to 36 weeks before joining this study.

I have not had radiation for cancer that has spread.

I understand the trial's nature and can give my written consent.

Exclusion Criteria

Patients undergoing therapy with other investigational agents

I do not have any severe ongoing health issues or uncontrolled infections.

I have had surgery to remove one or both of my testicles.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Deprivation Therapy (ADT)

Patients receive androgen deprivation therapy using goserelin acetate or leuprolide acetate and bicalutamide for up to 36 weeks

36 weeks

Every 4 or 12 weeks

Radiation Therapy

Patients undergo intensity-modulated radiation therapy daily for 2-7 weeks during or after completion of androgen deprivation therapy

2-7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 61.4 months

Every 4 weeks for 2 years, then every 3 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bicalutamide
• Goserelin Acetate
• Intensity-Modulated Radiation Therapy
• Leuprolide Acetate

Trial Overview The study tests if combining hormone therapy (goserelin, leuprolide acetate, bicalutamide) with targeted high-dose radiation (intensity-modulated radiation therapy) can better treat prostate cancer that has spread compared to standard treatments.

How Is the Trial Designed?

Group I: Treatment (androgen therapy, radiation therapy) Experimental Treatment 5 Interventions

ADT: Patients not currently on ADT receive goserelin acetate SC or leuprolide acetate via injection once every 4 or 12 weeks and bicalutamide PO QD. Treatment repeats every 12 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients already receiving ADT at the time of enrollment continue treatment until they have received 36 weeks of therapy. RADIATION THERAPY: Patients achieving PSA normalization after initiation of androgen deprivation therapy undergo intensity-modulated radiation therapy daily for 2-7 weeks during or after completion of androgen deprivation therapy.

Bicalutamide is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Casodex for:

• Metastatic prostate cancer

Approved in Japan as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A case study of a patient with castration-resistant prostate cancer showed that combining ablative stereotactic body radiation therapy with ongoing enzalutamide treatment resulted in a durable complete remission, despite prior progression on the medication.

This finding highlights the potential for innovative treatment strategies in advanced prostate cancer and suggests the need for further clinical trials to explore this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer. Nguyen, TC., Bajwa, R., Bari, S., et al.[2020]

In a study of 1,370 patients with locally advanced prostate cancer, bicalutamide 150 mg combined with radiotherapy significantly improved progression-free survival (PFS) by 44% and overall survival by 35% compared to radiotherapy alone, indicating its efficacy as an adjuvant therapy.

Bicalutamide also showed a substantial reduction in the risk of prostate-specific antigen (PSA) progression by 59%, making it a promising non-castration-based treatment option that offers quality-of-life benefits over traditional castration therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer. See, WA., Tyrrell, CJ.[2018]

Bicalutamide, when used in conjunction with radiation therapy, showed cytotoxic effects in androgen-dependent prostate cancer cells (LNCaP), leading to cell cycle arrest and reduced expression of prostate serum antigen (PSA) and androgen receptor (AR).

The study found that bicalutamide decreased the effectiveness of radiation in LNCaP cells, suggesting that it should not be administered close to radiation treatment to avoid antagonistic interactions, while showing an additive effect in androgen-independent DU145 cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells. Quéro, L., Giocanti, N., Hennequin, C., et al.[2014]

In a study of 40 patients with stages A2 to C prostatic cancer, leuprorelin acetate depot treatment resulted in 72% of patients showing major responses and 84% achieving normal prostate-specific antigen levels after 2 months.

The treatment effectively suppressed testosterone to castration levels, and while there were three deaths related to the disease, the protocol was well tolerated and showed effectiveness in managing advanced prostatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with leuprorelin acetate before radiotherapy for prostatic cancer. Bourdin, S., Karam, G., Clemain, P., et al.[2017]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[2023]

The ENZA-p trial is investigating the safety and efficacy of combining lutetium-177 (177 Lu)-PSMA-617 with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), aiming to improve prostate-specific antigen (PSA) progression-free survival (PFS) in high-risk patients.

This phase 2 trial will enroll 160 participants and assess various outcomes, including overall survival and quality of life, while also identifying potential biomarkers to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). Emmett, L., Subramaniam, S., Joshua, AM., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9643663/

A randomised comparison of 'Casodex' (bicalutamide) 150 ... Conclusions: 'Casodex' 150 mg is less effective than castration in patients with M1 disease. However, 'Casodex' has shown a benefit in terms of quality of life ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1569905602000830

Results from the Bicalutamide ('Casodex') EPC Programme Bicalutamide 150 mg significantly reduced the risk of objective progression by 42% (p⪡0.0001) compared with standard care alone. This effect was seen in ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2775631

Clinical Efficacy of Enzalutamide vs Bicalutamide ... Enzalutamide is associated with improved outcomes compared with bicalutamide, in terms of the rate and duration of PSA response, in Black patients with mHSPC.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9428389/

Bicalutamide (Casodex) in the treatment of prostate cancer A 150-mg daily dose is considered to provide equivalent survival outcome compared with castration in patients with locally advanced prostate cancer, whereas ...

5. valueinhealthjournal.com valueinhealthjournal.com/article/S1098-3015(10)60207-0/pdf

Cost-Effectiveness Analysis of Bicalutamide (Casodex™)* ... Conclusion: Based on the current data, bicalutamide appears to be a cost-effective option for adjuvant treat- ment of EPC. Keywords: adjuvant, bicalutamide, ...

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

Patient-reported outcomes of rezvilutamide versus ... In metastatic castration-resistant prostate cancer patients, clinical studies have demonstrated the promising efficacy and favorable safety ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.122

Outcomes, frailty status, and body composition of men with ... Only 3 patients have died, and 5-year OS is 81.3% for the entire cohort. Sarcopenia was found in 11 patients (52%) and sarcopenic obesity in 3 ( ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124000282

A 3-year Interim Analysis of the Observational J-ROCK Study Overall, seven patients (1.9%) in cohort 1 and ten (1.7%) in cohort 2 died from AEs (Table 3). Table 3. Safety outcomes in patients with high-risk metastatic ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00673205

(Bicalutamide) Casodex vs Placebo in Non-metastatic ... The purpose of this trial is to study the effect of adjuvant or immediate hormonal therapy, versus placebo, in subjects who have either undergone a primary ...