Combination Therapy for Metastatic Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must be taking: Androgen deprivation therapy

Must not be taking: Strong CYP3A inducers, Strong CYP3A inhibitors

Disqualifiers: Prior orchiectomy, Brain metastasis, Hepatitis, 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: Unknown

Duration: 24 months

21 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and effectiveness of radiation therapy with hormone therapy (ADT) and chemotherapy as an investigational study treatment for prostate cancer. This is a phase 2 study to deliver focal radiation with pulsed systemic therapy of Abiraterone, ADT and Lynparza (olaparib) in men with castration sensitive oligometastatic prostate cancer.

Do I need to stop taking my current medications to join the trial?

The trial requires a washout period (time without taking certain medications) for specific drugs. If you are taking strong or moderate CYP3A inducers or inhibitors, you will need to stop them for a certain period before starting olaparib. The washout period is 5 weeks for phenobarbital or enzalutamide and 3 weeks for other inducers, and 2 weeks for inhibitors.

What data supports the effectiveness of the drug combination therapy for metastatic prostate cancer?

Research shows that adding abiraterone acetate with prednisone to androgen deprivation therapy (ADT) significantly improves survival and quality of life for patients with metastatic prostate cancer. This combination has been effective in both hormone-sensitive and castration-resistant forms of the disease, indicating its broad applicability in improving patient outcomes. ^{1 2 3 4 5}

Is the combination therapy for metastatic prostate cancer safe for humans?

Abiraterone acetate (Zytiga) combined with prednisone has been shown to have an acceptable and manageable safety profile in clinical trials for metastatic castration-resistant prostate cancer. It is generally well-tolerated, with safety data supporting its use in patients who have or have not received chemotherapy. ^{6 7 8 9 10}

What makes the combination therapy for metastatic prostate cancer unique?

This treatment is unique because it combines multiple therapies, including abiraterone, which is an oral drug that blocks hormone production, with prednisone, ADT, radiotherapy, and olaparib, offering a comprehensive approach to improve survival and quality of life in patients with metastatic prostate cancer. ^{1 2 6 8 11}

Research Team

Zachery R. Reichert

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

Men with castration sensitive oligometastatic prostate cancer, who are medically fit for radiotherapy and have had prior prostate surgery or radiation. They must not have more than 5 metastatic sites suitable for radiation, no brain metastases, and an ECOG performance status of ≤1. Participants need normal organ function, a rising PSA level post-treatment, and agree to use contraception.

Inclusion Criteria

My organ and bone marrow functions are normal as tested within the last 28 days.

I am fully active and can carry on all my pre-disease activities without restriction.

I am a candidate for hormone therapy for my cancer, as advised by my oncologist.

Exclusion Criteria

Life expectancy ≤3 years in view of treating provider

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

I have been diagnosed with MDS, AML, or have symptoms that suggest these conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive focal radiation with pulsed systemic therapy of Abiraterone, ADT, and Lynparza

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long-term follow-up

Participants are monitored for long-term outcomes and adverse events

36 months

Treatment Details

Interventions

• Abiraterone
• Androgen Deprivation Therapy (ADT)
• External Beam Radiotherapy
• Olaparib
• Prednisone

Trial Overview The trial is testing the combination of focal radiation therapy with systemic hormone therapy (ADT) and chemotherapy drugs Abiraterone and Olaparib in men with limited spread prostate cancer. It's a phase 2 study aiming to see if this treatment can effectively manage the disease.

Participant Groups

Group I: Abiraterone, ADT, Radiation and Olaparib Experimental Treatment 5 Interventions

Abiraterone, ADT, radiation to all metastases and Olaparib.

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

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Findings from Research

Abiraterone acetate combined with prednisone significantly improves overall survival (34.7 months vs 30.3 months) and radiologic progression-free survival (16.5 months vs 8.3 months) in patients with metastatic castration-resistant prostate cancer compared to placebo.

The treatment is generally well-tolerated, with manageable side effects primarily related to mineral corticoid excess, and it also enhances the perceived quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] Juárez Soto, A., Caballero Cobos, R., Campanario Pérez, R., et al.[2018]

Adding abiraterone acetate plus prednisone/prednisolone (AAP) to androgen deprivation therapy (ADT) significantly reduces the risk of death in men with metastatic hormone-sensitive prostate cancer (mHSPC) by 38%, translating to a 14% absolute improvement in overall survival over three years, based on data from two major trials involving 82% of participants.

The addition of AAP also leads to a 55% reduction in the risk of clinical or radiological progression-free survival, with a 28% absolute improvement at three years, although there is an increased risk of certain grade III-IV toxicities, particularly cardiac and hepatic, without an increase in overall mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis. Rydzewska, LHM., Burdett, S., Vale, CL., et al.[2023]

In a real-world study involving 1108 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate plus prednisone (AAP) was found to be effective as both first-line and second-line treatment, with median overall survival of 27.1 months for first-line and 23.4 months for second-line therapy.

The treatment was well tolerated across all patient subgroups, including those with cardiovascular comorbidities, and no unexpected adverse events were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry. Bjartell, A., Lumen, N., Maroto, P., et al.[2021]

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

Oral abiraterone acetate (Zytiga®) effectively inhibits androgen biosynthesis, which is crucial for the progression of metastatic castration-resistant prostate cancer (mCRPC), and has been shown to prolong overall survival and radiographic progression-free survival in large phase 3 trials.

In combination with prednisone, abiraterone acetate has a manageable safety profile and is a convenient once-daily treatment option, making it a significant first-line therapy for men with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Scott, LJ.[2019]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

Intratumoral androgen biosynthesis is crucial in the development of metastatic castration-resistant prostate cancer (mCRPC), suggesting that these tumors continue to rely on androgens for growth even after androgen deprivation therapy.

A novel metabolite of abiraterone, D4A, shows strong antitumor effects by inhibiting androgen biosynthesis and blocking the androgen receptor, indicating its potential as a new treatment option for mCRPC, especially in cases resistant to existing therapies like enzalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in intratumoral androgen metabolism in castration-resistant prostate cancer. Penning, TM., Tamae, D.[2018]

Abiraterone is an effective treatment for metastatic castration-resistant prostate cancer (CRPC) as it targets both adrenal and tumor androgen production, addressing the issue of residual tumor androgens that contribute to cancer progression.

Phase III data supports its approval, and there is emerging evidence suggesting that abiraterone may also be beneficial in earlier stages of prostate cancer, indicating its potential for broader use beyond just CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical guide to the use of abiraterone in castration resistant prostate cancer. Mostaghel, EA., Lin, DW.[2023]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Abiraterone in castration resistant prostate cancer.] [2018]

2. England pubmed.ncbi.nlm.nih.gov

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis. [2023]

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

Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry. [2021]

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

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023]

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

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

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. [2019]

8. Sweden pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. [2017]

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

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. [2018]

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

Current advances in intratumoral androgen metabolism in castration-resistant prostate cancer. [2018]

11. Canada pubmed.ncbi.nlm.nih.gov

Practical guide to the use of abiraterone in castration resistant prostate cancer. [2023]