Combination Therapy for Metastatic Prostate Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Zachery R. Reichert

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Michigan Rogel Cancer Center Ann Arbor, MI

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center Lead Sponsor

References

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

[Abiraterone in castration resistant prostate cancer.] [2018] Prostate cancer is the most frequent neoplasia diagnosed in males. Treatment of metastatic prostate cancer is based on androgen deprivation therapy (ADT) up to its change to the castration resistance state. Recently, new molecules have been developed that significantly increase survival and quality of life of these patients. Abiraterone acetate in combination with prednisone is the first oral hormone therapy that contributed to this change in the approach of the disease.

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] There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT.

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] Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.

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

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022] Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.

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] Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival.

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021] Oral abiraterone acetate (Zytiga®), a selective cytochrome P450 17A1 enzyme inhibitor, is used in combination with prednisone or prednisolone to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel-containing chemotherapy. In a clinical trial in patients with CRPC, abiraterone acetate plus prednisone significantly prolonged overall survival, the time to prostate-specific antigen progression and progression-free survival compared with placebo plus prednisone.

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

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. [2019] Oral abiraterone acetate (Zytiga®) is a selective inhibitor of CYP17 and thereby inhibits androgen biosynthesis, with androgen signalling crucial in the progression from primary to metastatic prostate cancer (PC) and subsequently, in the development of metastatic castration-resistant PC (mCRPC). In large phase 3 trials and in the clinical practice setting, oral abiraterone acetate in combination with prednisone was an effective treatment and had an acceptable, manageable tolerability and safety profile in chemotherapy-naive and docetaxel-experienced men with mCRPC. In the pivotal global phase 3 trials, relative to placebo (+prednisone), abiraterone acetate (+prednisone) prolonged overall survival (OS) at data maturity (final analysis) and radiographic progression-free survival (rPFS) at all assessed timepoints. Given its efficacy in prolonging OS and its convenient once-daily oral regimen, in combination with prednisone, abiraterone acetate is an important first-line option for the treatment of mCRPC.

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] In a randomized clinical trial (COU-AA-301), abiraterone acetate (Zytiga(®)) was shown to be superior to prednisone in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the value of abiraterone treatment for patients with mCRPC in clinical practice in Sweden is not known. The aim of this study was to compare the outcomes and treatment patterns of abiraterone treatment in a Swedish observational study to those of the pivotal clinical trial, thereby discussing the external validity of the postchemotherapy clinical trial from a Swedish perspective.

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] On December 10, 2012, the U.S. Food and Drug Administration granted full approval for a modified indication for abiraterone acetate (Zytiga tablets; Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The approval was based on clinical trial COU-AA-302, which randomly allocated asymptomatic or mildly symptomatic patients with chemotherapy-naïve mCRPC and no visceral metastases to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N = 542). The coprimary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). The median rPFS was 8.3 months in the placebo arm and had not yet been reached in the abiraterone acetate arm {HR, 0.43 [95% confidence interval (CI) 0.35-0.52]; P

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

Current advances in intratumoral androgen metabolism in castration-resistant prostate cancer. [2018] Androgen deprivation therapy is a cornerstone in the treatment of advanced prostate cancer and has extended the lives of countless patients. Unfortunately, many of these patients eventually succumb to metastatic castration-resistant prostate cancer (mCRPC). The efficacy of abiraterone acetate (AA, Zytiga) and enzalutamide (Enza, Xtandi) in the mCRPC setting prove that these tumors remain androgen-driven. We review recent studies that have shown that intratumoral androgen biosynthesis plays a significant role in the ever-evolving mCRPC tumor and we discuss the therapeutic implications of these findings.

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

Practical guide to the use of abiraterone in castration resistant prostate cancer. [2023] While androgen deprivation therapy remains the primary treatment modality for patients with metastatic prostate cancer, treatment is uniformly marked by progression to castration resistant prostate cancer (CRPC). Abiraterone is the first new drug to enter clinical practice in a series of novel agents designed to potently target adrenal and tumor androgen production.