Radium-223 + Hormone Therapy + SBRT for Metastatic Prostate Cancer

Overseen By Savita Dandapani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: LHRH agonist/antagonist

Must not be taking: Chemotherapy

Disqualifiers: Brain metastases, Uncontrolled HIV, 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: 9

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 2 trial studies radium Ra 223 dichloride, hormone therapy and stereotactic body radiation in treating patients with prostate cancer that has spread to other places in the body. Radium Ra 223 dichloride contains a radioactive substance that collects in the bone and gives off radiation that may kill cancer cells. Hormone therapy using leuprolide acetate or goserelin acetate may fight prostate cancer by lowering the amount of testosterone the body makes. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving radium Ra 223 dichloride, hormone therapy and stereotactic body radiation may work better at treating prostate cancer.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like prior radium Ra 223 dichloride and chemotherapy for metastatic disease are not allowed. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Goserelin Acetate in treating metastatic prostate cancer?

Research shows that Goserelin Acetate effectively lowers testosterone levels to a range that helps manage advanced prostate cancer, with a 62% objective response rate in patients. It is considered effective, simple, and safe for treating advanced prostate cancer. ^{1 2 3 4 5}

Is the combination of Radium-223, hormone therapy, and SBRT safe for treating metastatic prostate cancer?

The hormone therapy component, specifically goserelin acetate (Zoladex), has been shown to be generally safe in humans for treating prostate cancer, with common side effects including increased triglyceride levels and hot flushes. In studies, adverse reactions were mostly mild and related to the drug's intended effects. ^{1 3 6 7 8}

What makes the Radium-223 + Hormone Therapy + SBRT treatment unique for metastatic prostate cancer?

This treatment is unique because it combines Radium-223, a radiopharmaceutical that specifically targets bone metastases to improve survival and quality of life, with hormone therapies like Goserelin and Leuprolide Acetate, which help manage hormone levels, and SBRT (stereotactic body radiation therapy), which precisely targets cancer cells. This combination aims to enhance the effectiveness of treatment for metastatic prostate cancer, particularly in cases with bone involvement. ^{2 9 10 11 12}

Research Team

Savita Dandapani, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for men with prostate cancer that has spread, who have started hormone therapy recently and have a life expectancy over 12 months. They should not have had chemotherapy for metastatic disease but may have tried one non-chemotherapy treatment. Men must be able to undergo radiation if they haven't already treated the primary tumor site, and their blood counts and liver function need to meet specific levels.

Inclusion Criteria

Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 14 days prior to day 1 of protocol therapy)

Platelets >= 100,000/mm^3 (to be performed within 14 days prior to day 1 of protocol therapy)

Total serum bilirubin =< 2 x upper limit of normal (ULN) (to be performed within 14 days prior to day 1 of protocol therapy)

Exclusion Criteria

I have previously received radium Ra 223 treatment.

I have or am receiving chemotherapy for cancer that has returned or spread, with some exceptions.

I am receiving radiation therapy targeted at my prostate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hormone Therapy

Participants receive leuprolide acetate or goserelin acetate, or degarelix for up to 32 weeks

32 weeks

Regular visits for hormone administration

Stereotactic Body Radiation Therapy (SBRT)

Participants undergo 3-5 fractions of SBRT every 40 hours over 7-21 days

1-3 weeks

3-5 visits for radiation therapy

Radium Ra 223 Dichloride Treatment

Participants receive radium Ra 223 dichloride intravenously on day 1 of courses 2-7

6 months

6 visits for radium administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular follow-up visits

Treatment Details

Interventions

• Goserelin Acetate
• Leuprolide Acetate
• Radium Ra 223 Dichloride
• Stereotactic Body Radiation Therapy

Trial Overview The study tests combining radium Ra 223 (a radioactive substance targeting bone metastases), hormone therapy (lowering testosterone), and stereotactic body radiation (precise high-dose radiation) in treating advanced prostate cancer. The goal is to see if this combination works better than current treatments.

Participant Groups

Group I: Treatment (hormone therapy, SBRT, radium Ra 223 dichloride) Experimental Treatment 6 Interventions

Beginning 4 weeks (28 days) prior to radiation therapy, patients receive leuprolide acetate or goserelin acetate, for up to 32 weeks. Patients also undergo 3-5 fractions of SBRT every 40 hours over 7-21 days beginning on day 1 of course 1, and receive radium Ra 223 dichloride IV over 1 minute on day 1 of courses 2-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

Goserelin Acetate is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Zoladex for:

• Breast cancer
• Prostate cancer
• Endometriosis
• Uterine fibroids

Approved in United States as Zoladex for:

• Advanced breast cancer
• Prostate cancer
• Endometriosis
• Uterine bleeding

Approved in Canada as Zoladex for:

• Breast cancer
• Prostate cancer
• Endometriosis

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Findings from Research

Radium-223 is an effective treatment for bone metastatic castration-resistant prostate cancer, improving overall survival and quality of life, as demonstrated in a Phase III randomized placebo-controlled study.

Unlike traditional chemotherapy, radium-223 specifically targets bone metastases and can be administered without complex shielding, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer - role of radium-223. Mukherji, D., El Dika, I., Temraz, S., et al.[2021]

References

1. Austria pubmed.ncbi.nlm.nih.gov

[Chemical castration using a depot LHRH-agonist as a palliative therapy concept in prostatic carcinoma--clinical, endocrinological and experimental studies]. [2013]

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

Efficacy of a second line luteinizing hormone-releasing hormone agonist after advanced prostate cancer biochemical recurrence. [2013]

3. 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]

4. 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]

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

A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. The International Prostate Cancer Study Group. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot) in advanced prostate cancer: results from an Italian, open, multicenter trial. [2017]

7. 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]

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

[Clinical effects of a 3-month formulation LH-RH agonist (Zoladex LA 10.8 mg depot) in patients with prostate cancer]. [2022]

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

Radium-223 Therapy of Bone Metastases in Prostate Cancer. [2017]

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

Three years' clinical practice of Radium-223 therapy in patients with symptomatic bone metastases from metastatic castrate-resistant prostate cancer: a single-centre experience. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer - role of radium-223. [2021]

12. Greece pubmed.ncbi.nlm.nih.gov

Risk Scoring System for Ra-223 Discontinuation and Its Effect on Prognosis: A Retrospective Study. [2022]