Hormone + Radiation Therapy for Metastatic Prostate Cancer

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

29 Participants Needed

Trial Summary

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.

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

Research shows that Zoladex, a hormone therapy, effectively reduces testosterone levels, which can help manage prostate cancer. Additionally, combining intensity-modulated radiotherapy (IMRT) with hormone therapy like Casodex and Zoladex has been shown to improve quality of life in patients with advanced prostate cancer. ^{1 2 3 4 5}

Is hormone and radiation therapy for metastatic prostate cancer generally safe for humans?

The treatments, including Zoladex (goserelin acetate) and Casodex (bicalutamide), have been generally well-tolerated in clinical trials for prostate cancer. Common side effects include hot flashes and decreased libido, but no severe side effects required stopping the treatment. Safety profiles were similar across different formulations and dosages. ^{1 6 7 8 9}

How is the treatment for metastatic prostate cancer using hormone and radiation therapy unique?

This treatment combines hormone therapy with radiation, using drugs like Bicalutamide and Goserelin Acetate, which can improve survival rates compared to radiation alone. Bicalutamide is a non-castration-based therapy that can be taken orally, offering an alternative to traditional castration methods, and is often well-tolerated with fewer side effects. ^{1 10 11 12 13}

What is the purpose of this trial?

This phase II trial studies how well hormone therapy and intensity-modulated radiation therapy work in treating patients with prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Anti-hormone therapy using goserelin, leuprolide acetate, or bicalutamide, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving hormone therapy and intensity-modulated radiation therapy may work better in treating patients with prostate cancer.

Research Team

Cy A Stein

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

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

Patients undergoing therapy with other investigational agents

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Zoladex (ICI 118,630): clinical trial of new luteinizing hormone-releasing hormone analog in metastatic prostatic carcinoma. [2019]

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

Long-term quality of life outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with androgen deprivation. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Clinical experience with leuprorelin acetate before radiotherapy for prostatic cancer. [2017]

4. United States 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. [2023]

5. England 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). [2022]

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

The non-steroidal antiandrogen, bicalutamide ('Casodex'), may preserve bone mineral density as compared with castration: results of a preliminary study. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[A new LH-RH agonist for treatment of prostate cancer, 3-month controlled-release formulation of goserelin acetate (Zoladex LA 10.8 mg depot)--outline of pre-clinical and clinical studies]. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

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

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

Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells. [2014]

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

A randomised comparison of monotherapy with Casodex 50 mg daily and castration in the treatment of metastatic prostate carcinoma. Casodex Study Group. [2019]