Olaparib + Abiraterone for Prostate Cancer

Not currently recruiting at 166 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding olaparib (Lynparza, a targeted cancer therapy) to abiraterone (Zytiga, a hormonal therapy) improves treatment for metastatic castration-resistant prostate cancer compared to using abiraterone alone. The researchers aim to determine if this combination is more effective and safe for patients whose prostate cancer has spread and who have not yet received chemotherapy or new hormonal treatments. The trial seeks participants with prostate cancer that continues to progress despite other treatments and who are suitable for abiraterone therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of olaparib and abiraterone is generally well-tolerated by patients with advanced prostate cancer that no longer responds to hormone therapy. Earlier studies demonstrated that this combination reduced the risk of cancer progression or death by 34% compared to standard treatments, indicating relative safety.

However, some patients experienced side effects. Common side effects included nausea, fatigue, and low red blood cell levels (anemia). These were usually manageable with supportive care, such as dose adjustments or additional medications.

Olaparib has been used in other cancer treatments and received FDA approval for certain conditions, providing reassurance about its safety. Overall, despite side effects, the treatment has been deemed safe enough for advanced testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike the standard of care for prostate cancer, which typically involves hormone therapies like abiraterone alone, the combination of olaparib and abiraterone is unique because it harnesses the power of a PARP inhibitor. Olaparib targets cancer cells by preventing them from repairing their DNA, which could lead to more effective cancer cell death. Researchers are excited because this dual approach might enhance treatment efficacy and offer new hope for patients with advanced prostate cancer.

What evidence suggests that this trial's treatments could be effective for metastatic castration-resistant prostate cancer?

Research has shown that using olaparib with abiraterone may help treat metastatic castration-resistant prostate cancer (mCRPC). In this trial, one group of participants will receive this combination. The PROpel study found that this combination helped patients live longer without their cancer worsening compared to using abiraterone alone. Another study reported that patients taking both drugs lived an average of 42.1 months, while those taking only abiraterone lived about 34.7 months. Previous research also found that olaparib alone improved survival in some prostate cancer patients, especially those with certain genetic changes like BRCA1 or BRCA2. This combination works well because olaparib makes it harder for cancer cells to repair themselves, enhancing the effectiveness of abiraterone. ^{1 2 6 7 8}

Who Is on the Research Team?

Fred Saad, MD

Principal Investigator

University of Montreal Hospital Center

Noel Clarke, M.D.

Principal Investigator

Christie Hospital Foundation Trust

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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®) 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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10587563/

Efficacy and safety of olaparib combined with abiraterone ... In the phase III PROfound study (NCT02987543), olaparib monotherapy showed clinical improvement in radiographic progression-free survival (rPFS) ...

2. lynparza.com lynparza.com/prostate-cancer/results.html

Metastatic Prostate Cancer Treatment Results The median time of survival after the start of LYNPARZA was 19.1 months vs 14.7 months on enzalutamide or abiraterone. FOR ADULTS WITH BRCA1, BRCA2, OR ATM ...

3. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200043

Abiraterone and Olaparib for Metastatic Castration-Resistant ... At primary analysis at this first data cutoff, abiraterone combined with olaparib significantly prolonged ibPFS compared with abiraterone and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124000828

Tolerability of Olaparib Combined with Abiraterone in ... The PROpel study (NCT03732820) demonstrated a statistically significant progression-free survival benefit with olaparib plus abiraterone versus placebo plus ...

5. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-prostate-cancer/149313-asco-gu-2024-efficacy-of-olaparib-plus-abiraterone-versus-placebo-plus-abiraterone-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-with-single-homologous-recombination-repair-gene-mutations-in-the-propel-trial.html

ASCO GU 2024: Efficacy of Olaparib plus Abiraterone ... In an updated report at a median follow-up of 36.6 months, the median overall survival was 42.1 months with olaparib plus abiraterone and 34.7 ...

6. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2022/lynparza-olaparib-plus-abiraterone-reduced-risk-of-disease-progression-by-34-vs-standard-of-care-in-1st-line-metastatic-castration-resistant-prostate-cancer-02142022.html

LYNPARZA® (olaparib) plus abiraterone reduced risk of ... In a predefined interim analysis, LYNPARZA in combination with abiraterone reduced the risk of disease progression or death by 34% versus ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2588931123002183

Olaparib plus Abiraterone for Metastatic Castration- ... A positive phase 3 trial that demonstrated a clinically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01972217

NCT01972217 | Ph II Study to Evaluate Olaparib With ... This is a 2-part study in patients with metastatic CRPC. Part A is an open-label safety run-in study to assess the safety, tolerability and PK of olaparib when ...