Olaparib for Breast Cancer

(OlympiA Trial)

Not currently recruiting at 675 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Second primary malignancy, Metastatic cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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: 1

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug olaparib can help treat individuals with a specific type of breast cancer that is HER2 negative and linked to BRCA1 or BRCA2 gene mutations. The researchers aim to determine if olaparib benefits those who have already completed surgery and chemotherapy. Participants will receive either olaparib (also known as Lynparza) or a placebo to compare outcomes. Ideal candidates have previously undergone breast cancer surgery and chemotherapy and have a confirmed BRCA1 or BRCA2 gene mutation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. If you are using strong or moderate CYP3A inhibitors or inducers, you will need to stop them for a specific period (2 to 5 weeks) before starting the study treatment.

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

Research shows that olaparib is generally safe for patients. In earlier studies, olaparib showed positive results for people with BRCA mutations, a genetic change linked to breast cancer. Participants who took olaparib experienced fewer deaths compared to those on a placebo, with 59 deaths in the olaparib group and 86 in the placebo group. This suggests that olaparib may be safer.

Additionally, olaparib has been used for other conditions, demonstrating long-term benefits and high survival rates. In one study, 87.5% of patients treated with olaparib were alive after six years. While some side effects like nausea or tiredness can occur, extensive research supports olaparib's safety. ^{1 2 3 4 5}

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

Olaparib is unique because it specifically targets and inhibits the enzyme PARP, which plays a role in repairing damaged DNA in cells. Unlike traditional chemotherapy that attacks fast-growing cells in general, Olaparib zeroes in on cancer cells with specific genetic mutations, causing them to die while minimizing harm to normal cells. This precision approach offers hope for more effective treatment with potentially fewer side effects, making it an exciting option for those with certain types of breast cancer.

What evidence suggests that Olaparib might be an effective treatment for breast cancer?

Research has shown that Olaparib, which participants in this trial may receive, effectively treats breast cancer, particularly in patients with BRCA1/2 gene mutations. One study found that 87.5% of patients taking Olaparib were alive after six years, compared to 83.2% in the group not taking it. Olaparib reduced the risk of death by 32% for patients with early breast cancer compared to a placebo. It also prolonged the time before the cancer worsened in patients with certain types of breast cancer. These findings suggest that Olaparib could be a promising treatment option for breast cancer patients with specific genetic mutations. ^{2 6 7 8 9}

Who Is on the Research Team?

Charles Geyer, Doctor of Medicine

Principal Investigator

Virginia Commonwealth University Massey Cancer Center, McGlothlin Medical Education Center, Room 12-217, 1201 East Marshall St., PO Box 980070, Richmond, VA 23298-0070, USA

Andrew Tutt, Doctor of Medicine

Principal Investigator

Integrated Cancer Centre Guy's Hospital, King's College, London School of Medicine, London, UK

Judy Garber, Doctor of Medicine

Principal Investigator

Harvard Medical School, Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Susan F. Smither Center for Women's Cancers, 450 Brookline Avenue, Boston; MA 02215, US

Are You a Good Fit for This Trial?

This trial is for adults with high-risk HER2 negative breast cancer who have a BRCA1/2 mutation. They must have finished at least 6 cycles of certain chemotherapies and surgery, not be on strong CYP3A inhibitors or inducers, and can't have had prior treatment with PARP inhibitors like olaparib.

Inclusion Criteria

I have a harmful BRCA1 or BRCA2 gene mutation.

I've completed 6 or more cycles of chemotherapy with anthracyclines, taxanes, or both.

My breast cancer is invasive and not spread to other parts.

Exclusion Criteria

Known hypersensitivity to any of the excipients of study treatment

I have never been treated with a PARP inhibitor like olaparib.

I have another cancer type but it's either treated, was caught early, or happened over 5 years ago with no recurrence.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Randomised patients receive olaparib or placebo for up to 12 months with safety assessments every 2 weeks during the first month, every 4 weeks for the following 5 months, and every 3 months for the remaining 6 months

12 months

Bi-weekly visits for 1 month, monthly visits for 5 months, quarterly visits for 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with efficacy assessments every 3 months for the first 2 years, then every 6 months for years 3-5, and annually thereafter

10 years

Annual visits for mammogram/breast MRI

Survival Follow-up

Participants enter the survival follow-up phase after completing 10 years of clinical assessment, continuing until approximately 10 years after the last patient is randomised

Approximately 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Placebo

Trial Overview The study tests Olaparib as an additional (adjuvant) therapy against a placebo in patients with specific genetic mutations after they've completed initial treatments for breast cancer. The goal is to see if Olaparib can prevent cancer from coming back.

How Is the Trial Designed?

Group I: Olaparib Experimental Treatment 1 Intervention

Olaparib tablets 300mg b.i.d. p.o.

Group II: Placebo Placebo Group 1 Intervention

Placebo tablets b.i.d. p.o.

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

The Breast Adjuvant Study Team

Collaborator

Trials

1

Recruited

1,800+

Breast International Group

Collaborator

Trials

34

Recruited

53,600+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Myriad Genetic Laboratories, Inc.

Industry Sponsor

Trials

32

Recruited

14,600+

Frontier Science & Technology Research Foundation, Inc.

Industry Sponsor

Trials

8

Recruited

7,400+

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

Br.E.A.S.T. -Data Center & Operational Office Institut Jules Bordet

Collaborator

Trials

1

Recruited

1,800+

Published Research Related to This Trial

Olaparib, an oral PARP-inhibitor, significantly improves progression-free survival in HER2-negative advanced breast cancer patients with BRCA1/2 mutations compared to standard chemotherapy, based on a randomized Phase III trial.

The trial also indicated an overall survival benefit for patients who had not received prior chemotherapy for metastatic disease, highlighting olaparib's potential as an effective treatment option in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. Griguolo, G., Dieci, MV., Miglietta, F., et al.[2021]

In a phase I study involving 79 patients, the combination of the PARP inhibitor olaparib with endocrine therapies (tamoxifen, anastrozole, or letrozole) was found to be generally safe and well tolerated, with no significant pharmacokinetic interactions between the drugs.

While tamoxifen slightly decreased olaparib exposure, the overall safety profile remained acceptable, indicating that these combinations could be a viable treatment option for patients with advanced solid tumors, including breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Effects and Safety of Olaparib Administered with Endocrine Therapy: A Phase I Study in Patients with Advanced Solid Tumours. Plummer, R., Verheul, HM., De Vos, FYFL., et al.[2019]

In the OlympiA trial involving 1,836 patients with early breast cancer and gBRCA1/2 pathogenic variants, olaparib significantly improved overall survival (OS) compared to placebo, with a 4-year OS rate of 89.8% versus 86.4%.

The study also maintained significant improvements in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS), with no new safety concerns identified, indicating that olaparib is a safe and effective adjuvant therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Geyer, CE., Garber, JE., Gelber, RD., et al.[2023]

Olaparib is a powerful inhibitor of PARP-1 and PARP-2, showing effectiveness in treating ovarian cancer, particularly in patients with germline BRCA mutations.

Phase III trials are currently evaluating olaparib's efficacy as a maintenance therapy after initial treatment in patients with BRCA mutations, highlighting its potential role in long-term cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. Gunderson, CC., Moore, KN.[2016]

Olaparib is an oral medication that inhibits poly (ADP-ribose) polymerase and is primarily developed for treating BRCA mutation-positive ovarian cancer, with its capsule formulation already approved in the EU and USA.

The drug is currently undergoing extensive clinical trials for various cancers, including breast, gastric, and pancreatic cancers, indicating its potential broad application in oncology beyond ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib: first global approval. Deeks, ED.[2020]

The combination of olaparib and carboplatin was found to be safe and effective in treating breast and ovarian cancer in patients with germline BRCA1 or BRCA2 mutations, with 50% of patients showing a partial response and one patient achieving a complete response.

Proteomic analysis indicated that high levels of FOXO3a expression before treatment may predict a better response to the therapy, suggesting a potential biomarker for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. Lee, JM., Hays, JL., Annunziata, CM., et al.[2022]

Olaparib, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

In the phase III OlympiAD trial, olaparib significantly improved progression-free survival (PFS) in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer, with a median PFS of 8.0 months compared to 3.8 months for chemotherapy, indicating a strong efficacy of olaparib.

Subgroup analyses showed consistent benefits of olaparib across various patient characteristics, including hormone receptor status and prior chemotherapy, with higher objective response rates and improved quality of life compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial. Senkus, E., Delaloge, S., Domchek, SM., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39544591/

Real-World Clinical Outcomes of Treatment With Olaparib ... Olaparib is effective in the treatment of metastatic breast cancer (MBC) patients, mainly confirmed by deleterious germline BRCA mutations.

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

LYNPARZA® (olaparib) demonstrated clinically meaningful ... 87.5% of patients treated with LYNPARZA were alive at six years vs. 83.2% in the comparator arm. First and only PARP inhibitor to improve ...

3. lynparza.com lynparza.com/breast-cancer/results/early-breast-cancer.html

Early Breast Cancer - Clinical Study Results of ... LYNPARZA lowered the risk of death by 32% in early breast cancer compared with placebo. In this study, 846 out of 921 patients treated with LYNPARZA were alive ...

4. lynparzahcp.com lynparzahcp.com/breast-cancer/efficacy/olympiad.html

LYNPARZA® (olaparib) Efficacy for gBRCAm, HER2-negative ... LYNPARZA significantly improved PFS vs physician's choice of chemotherapy in the OlympiAD trial. 1,2 Primary endpoint: progression-free survival.

5. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/lynparza-demonstrated-clinically-meaningful-prolonged-survival-benefit-in-early-breast-cancer-in-olympia-phase-iii-trial.html

Lynparza demonstrated clinically meaningful prolonged ... 87.5% of patients treated with Lynparza were alive at six years vs. 83.2% in the comparator arm. First and only PARP inhibitor to improve ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10948524/

Clinical effectiveness and safety of olaparib in BRCA-mutated ... The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated ...

7. dana-farber.org dana-farber.org/newsroom/news-releases/2024/parp-inhibition-shows-long-term-survival-benefits-for-patients-with-high-risk-brca-positive-breast-cancer

PARP Inhibition Shows Long-term Survival Benefits for ... After a median follow-up of 6.1 years, patients treated with olaparib continued to show significant improvements in survival outcomes, in both ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2105215

Adjuvant Olaparib for Patients with BRCA1- or BRCA2- ... Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, ...

9. lynparzahcp.com lynparzahcp.com/breast-cancer/safety-tolerability/olympiad.html

gBRCAm, HER2-Negative, Metastatic Breast Cancer Learn about the safety and tolerability for LYNPARZA® (olaparib) in the OlympiAD trial for patients with gBRCAm, HER2-negative, metastatic breast cancer.