Combination Therapy for Prostate Cancer

Recruiting at 10 trial locations

Overseen By Sean McBride, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: GnRH analogs

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: Malignancy, Brain metastasis, Hypertension, 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: Unknown

Duration: 6 months

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is to find out whether adding the study drug atezolizumab and stereotactic body radiotherapy (SBRT) to standard treatment with abiraterone acetate, prednisone, and Lupron® (leuprolide) is a safe and effective way to treat previously untreated metastatic prostate cancer, and to see whether the study treatment works better than the standard treatment.

Will I have to stop taking my current medications?

The trial requires that participants stop taking anti-androgens like bicalutamide (Casodex) before starting the study. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

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

The combination of abiraterone acetate and enzalutamide has been shown to improve outcomes for patients with metastatic prostate cancer when added to androgen deprivation therapy, according to the STAMPEDE trials. ^{1 2 3 4 5}

Is the combination therapy for prostate cancer safe for humans?

The combination of abiraterone acetate with prednisone and enzalutamide has been studied for safety in patients with metastatic castration-resistant prostate cancer. These treatments are generally considered safe, but they can have side effects, and their tolerability may vary among individuals. ^{1 4 6 7 8}

How is the combination therapy of Abiraterone, Atezolizumab, and Enzalutamide unique for prostate cancer?

This combination therapy is unique because it combines Abiraterone and Enzalutamide, which target androgen receptors (proteins that bind male hormones), with Atezolizumab, an immunotherapy drug that helps the immune system attack cancer cells. This approach aims to address resistance mechanisms in prostate cancer by using both hormonal and immune system strategies. ^{1 2 5 6 9}

Research Team

Dana Rathkopf, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Men over 18 with untreated metastatic hormone-sensitive prostate cancer, who can consent to treatment and have normal organ function. They must be eligible for SBRT, have an ECOG status of 0 or 1, and agree to use birth control during the study. Exclusions include HIV/HBV/HCV infection, large prostate volume (>80cc), certain allergies, other recent cancers or treatments, uncontrolled conditions like hypertension or infections.

Inclusion Criteria

My prostate cancer was confirmed through a biopsy.

Willing and able to provide or have a legally authorized representative to provide written informed consent and HIPAA authorization for the release of personal health information

Subjects must agree to use a medically acceptable method of birth control or sexual abstinence for the duration of the study, including 150 days after the last dose of study drug

Exclusion Criteria

Treatment with investigational therapy within 28 days prior to initiation of study treatment

I haven't had major heart problems in the last 6 months.

I have brain metastasis or active leptomeningeal disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with atezolizumab, abiraterone acetate, prednisone, GnRH analog, and SBRT

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Abiraterone
• Atezolizumab
• Enzalutamide
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The trial is testing if adding atezolizumab (an immunotherapy drug) and SBRT to standard treatment with abiraterone acetate (a hormonal therapy), prednisone (a steroid), and Lupron® improves outcomes in men with newly diagnosed metastatic prostate cancer compared to standard treatment alone.

Participant Groups

Group I: Metastatic Prostate Cancer Experimental Treatment 7 Interventions

Participants will have untreated metastatic (M1a/b/c) hormone-sensitive prostate cancer documented by positive bone scan or metastatic lesion on CT or MRI; untreated is defined as having never received surgical, radiotherapeutic, or systemic therapy for their prostate cancer.Group 1 and 2. The first 20 patients enrolled will be in Group 1 and the remaining patients (and those who are already on a GnRH analog) will be assigned to Group 2. All study participants will receive treatment with atezolizumab, abiraterone acetate, prednisone, GnRH analog, and SBRT, at the same doses.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Findings from Research

Combining atezolizumab, an anti-PD-L1 immunotherapy, with enzalutamide, an androgen receptor antagonist, did not improve survival rates in patients with metastatic prostate cancer.

Further research is needed to understand the mechanisms of resistance to immunotherapy in the prostate tumor microenvironment, which may help improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. Siddiqui, BA., Subudhi, SK., Sharma, P.[2023]

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]

In a study of 133 patients with non-metastatic castration-resistant prostate cancer, abiraterone acetate (AA) plus prednisone showed comparable overall survival and cancer-specific survival to enzalutamide (Enz) over a median follow-up of 36 months.

However, patients treated with AA plus prednisone had a significantly higher risk of non-cancer-caused death compared to those treated with Enz, suggesting that while both treatments are effective, AA plus prednisone may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. Tsujino, T., Tokushige, S., Komura, K., et al.[2023]

In a study of 100 patients with metastatic castration-resistant prostate cancer, those treated with enzalutamide (ENZA) reported significantly more fatigue and neurocognitive issues compared to those treated with abiraterone acetate plus prednisone (AA+P).

While both treatments had similar rates of severe adverse events, ENZA was associated with unique neuropsychiatric side effects such as memory impairment and confusion, indicating a need for careful monitoring of cognitive function in patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). Shore, ND., Saltzstein, D., Sieber, P., et al.[2021]

In a study involving 132 patients with metastatic castration-resistant prostate cancer, the combination of cabozantinib and atezolizumab demonstrated an objective response rate of 23%, indicating promising antitumor activity after prior hormonal therapies.

While the treatment showed efficacy, 55% of patients experienced grade 3-4 treatment-related adverse events, with pulmonary embolism and diarrhea being the most common, suggesting that while the combination is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). Agarwal, N., McGregor, B., Maughan, BL., et al.[2022]

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]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

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]

RNA sequencing of circulating tumor cells (CTCs) from patients treated with abiraterone or enzalutamide revealed mutations in the androgen receptor and identified the TGFβ and cyclin D1 signaling pathways as key players in resistance to these therapies.

Targeting the downstream effects of SMAD3 and CCND1 may offer new treatment strategies for patients with metastatic castration-resistant prostate cancer who develop resistance to current androgen receptor-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of mechanisms of resistance to treatment with abiraterone acetate or enzalutamide in patients with castration-resistant prostate cancer (CRPC). Pal, SK., Patel, J., He, M., et al.[2021]

References

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

Anti-PD-L1 plus enzalutamide does not improve overall survival in prostate cancer. [2023]

2. 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]

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

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. [2023]

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

Results of a Real-world Study of Enzalutamide and Abiraterone Acetate With Prednisone Tolerability (REAAcT). [2021]

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

Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). [2022]

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

8. 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]

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

Identification of mechanisms of resistance to treatment with abiraterone acetate or enzalutamide in patients with castration-resistant prostate cancer (CRPC). [2021]