Olaparib + Abiraterone for Prostate Cancer

Recruiting at 132 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Androgen deprivation therapy

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Additional malignancy, Cardiovascular disease, Hypertension, Brain metastases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Approx. 3 years 11 months

895 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety (including evaluating side effects) of combination of olaparib and abiraterone versus placebo and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have received no prior cytotoxic chemotherapy or new hormonal agents (NHAs) at metastatic castration-resistant prostate cancer (mCRPC) stage.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some drugs. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them 2 to 5 weeks before starting the study treatment, depending on the specific medication. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination of Olaparib and Abiraterone for prostate cancer?

Research shows that combining Olaparib with Abiraterone significantly improves progression-free survival (the time during which the cancer does not get worse) in patients with metastatic castration-resistant prostate cancer compared to using Abiraterone alone. ^{1 2 3 4 5}

Is the combination of Olaparib and Abiraterone safe for humans?

The combination of Olaparib and Abiraterone has been studied in patients with metastatic castration-resistant prostate cancer, and safety data from these studies suggest it is generally safe for use in humans. However, as with any treatment, there may be side effects, and it's important to discuss these with your doctor. ^{1 2 4 5 6}

How is the drug combination of Olaparib and Abiraterone unique for treating prostate cancer?

The combination of Olaparib and Abiraterone is unique because it targets prostate cancer by combining a PARP inhibitor (Olaparib) with an androgen pathway inhibitor (Abiraterone), which has shown improved progression-free survival in patients with metastatic castration-resistant prostate cancer, regardless of specific genetic mutations. ^{1 2 5 6 7}

Research Team

Fred Saad, MD

Principal Investigator

University of Montreal Hospital Center

Noel Clarke, M.D.

Principal Investigator

Christie Hospital Foundation Trust

Eligibility Criteria

Men over 18 with metastatic castration-resistant prostate cancer who haven't had chemotherapy or new hormonal agents for this stage of cancer. They must be on androgen deprivation therapy, have normal organ and bone marrow function, an ECOG status of 0-1, a life expectancy of at least 6 months, and agree to use contraception. Those with other active cancers, heart issues, uncontrolled conditions or infections are excluded.

Inclusion Criteria

I have given my consent for genetic research.

I have given my consent for biomarker research.

My prostate cancer was confirmed through a tissue test.

Exclusion Criteria

I do not have any conditions that prevent me from taking prednisone.

I am scheduled for heart surgery or a procedure to open my heart's arteries.

I haven't had chemotherapy or radiotherapy (except for comfort care) in the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral treatment with olaparib plus abiraterone or placebo plus abiraterone, along with prednisone or prednisolone

Approx. 3 years 11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Abiraterone Acetate
• Olaparib

Trial Overview The trial is testing the effectiveness and safety of combining olaparib with abiraterone versus placebo plus abiraterone in men with mCRPC. It aims to see if this combination can help control the cancer better without causing severe side effects.

Participant Groups

Group I: olaparib plus abiraterone Experimental Treatment 2 Interventions

Olaparib is available as a film-coated tablet containing 100 milligrams (mg) or 150 milligrams (mg) of olaparib. Subjects will be administered olaparib orally at a dose of 300 milligrams (mg) twice daily (bid). The initial dosage of 300 milligrams (mg) twice daily will be composed of 2 x 150 milligrams (mg) tablets per dose. The 100 milligrams (mg) and 150 milligrams (mg) tablets will be used to manage dose reductions during the study. Abiraterone acetate with prednisone or prednisolone will be sourced locally as commercially available materials. Subjects will be administered abiraterone orally at a dose of 1000 milligrams (mg) once daily, in combination with prednisone or prednisolone 5 milligrams (mg) administered orally twice daily.

Group II: placebo plus abiraterone Placebo Group 1 Intervention

Placebo to match olaparib is available as a film-coated tablet in 100 milligrams (mg) or 150 milligrams (mg). Subjects will be administered placebo orally at a dose of 300 milligrams (mg) twice daily (bid). The initial dosage of 300 milligrams (mg) twice daily will be composed of 2 x 150 milligrams (mg) tablets per dose. The 100 milligrams (mg) and 150 milligrams (mg) tablets will be used to manage dose reductions during the study. Abiraterone acetate with prednisone or prednisolone will be sourced locally as commercially available materials. Subjects will be administered abiraterone orally at a dose of 1000 milligrams (mg) once daily, in combination with prednisone or prednisolone 5 milligrams (mg) administered orally twice daily.

Abiraterone Acetate 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
• Metastatic high-risk castration-sensitive prostate cancer

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Newly diagnosed high-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in Japan as Zytiga for:

• Prostate cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The combination of olaparib and abiraterone significantly improves radiographic progression-free survival and other key progression metrics in patients with metastatic castration-resistant prostate cancer, based on a meta-analysis of two randomized controlled trials involving 938 patients.

While the combination therapy shows efficacy, it is associated with a higher risk of high-grade anemia compared to monotherapy, indicating a need for careful management of treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized controlled trials. Luo, Z., Zhu, B., Xu, H., 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]

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]

In a phase 2 trial involving 142 patients with metastatic castration-resistant prostate cancer, the combination of olaparib and abiraterone significantly improved progression-free survival compared to placebo plus abiraterone, indicating its potential efficacy in extending patient survival.

However, exploratory analyses showed no significant differences in pain levels or health-related quality of life between the two treatment groups, suggesting that while the combination therapy may improve survival, it does not necessarily enhance the quality of life or reduce pain for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration-resistant prostate cancer: a randomised, double-blind, phase 2 trial. Saad, F., Thiery-Vuillemin, A., Wiechno, P., et al.[2022]

In a phase 2 trial involving 142 patients with metastatic castration-resistant prostate cancer, the combination of olaparib and abiraterone significantly improved radiographic progression-free survival (rPFS) to a median of 13.8 months compared to 8.2 months with placebo and abiraterone, indicating enhanced efficacy of the treatment.

While the combination treatment showed clinical benefits, it also resulted in a higher incidence of serious adverse events, including a treatment-related death, suggesting that while effective, the combination may carry increased risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Clarke, N., Wiechno, P., Alekseev, B., et al.[2019]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized controlled trials. [2023]

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

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

3. 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]

4. 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]

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

Patient-reported outcomes with olaparib plus abiraterone versus placebo plus abiraterone for metastatic castration-resistant prostate cancer: a randomised, double-blind, phase 2 trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. [2019]

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

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