Olaparib for Breast Cancer

(OlympiA Trial)

Recruiting at 601 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

1837 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Olaparib for breast cancer?

Research shows that Olaparib, a drug used for breast cancer, significantly extends the time patients live without their cancer getting worse compared to standard chemotherapy. It is particularly effective for patients with specific genetic mutations (BRCA1/2) and has shown benefits in both advanced and early stages of breast cancer. ^{1 2 3 4 5}

Is Olaparib safe for humans?

Olaparib (Lynparza) has been shown to have a manageable safety profile in clinical trials for breast cancer, meaning that while it can cause side effects, they are generally considered tolerable. It has been tested in various studies and is used for certain types of breast cancer, indicating it is generally safe for human use. ^{1 2 4 6 7}

How is the drug Olaparib unique for treating breast cancer?

Olaparib is unique because it is an oral medication specifically designed for patients with BRCA-mutated breast cancer, and it works by inhibiting PARP enzymes, which help repair DNA damage in cancer cells. This makes it particularly effective for certain types of breast cancer, like triple-negative breast cancer, where traditional chemotherapy might not be as effective. ^{4 7 8 9 10}

What is the purpose of this trial?

Olaparib treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 (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]

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]

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. [2021]

2. United States 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. [2023]

3. England 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. [2023]

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

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

5. United States 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. [2019]

6. United States 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

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

Olaparib: first global approval. [2020]

9. England pubmed.ncbi.nlm.nih.gov

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

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

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]