Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer (OlympiaN)
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ClinicalTrials.gov Identifier: NCT05498155 |
Recruitment Status :
Active, not recruiting
First Posted : August 11, 2022
Last Update Posted : May 9, 2024
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Tracking Information | |||||
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First Submitted Date ICMJE | July 5, 2022 | ||||
First Posted Date ICMJE | August 11, 2022 | ||||
Last Update Posted Date | May 9, 2024 | ||||
Actual Study Start Date ICMJE | November 7, 2022 | ||||
Estimated Primary Completion Date | May 2, 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
To evaluate the efficacy, measured by pCR (pathological complete response) rate, of olaparib monotherapy and olaparib plus durvalumab combination therapy, as assessed by central pathology review. [ Time Frame: Approx. 4 to 6 months ] pCR is defined as ypT0/Tis ypN0 (ie, no invasive residual in breast and the axillary lymph nodes on evaluation of the complete resected breast specimen and all sampled regional lymph nodes) following completion of neoadjuvant systemic therapy.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer | ||||
Official Title ICMJE | A Phase II, Multicentre, Open-Label Study to Assess the Efficacy and Safety of Olaparib Monotherapy and Olaparib Plus Durvalumab Combination as Neoadjuvant Therapy in Patients With BRCA Mutations and Early Stage HER2-Negative Breast Cancer | ||||
Brief Summary | This study to learn more about olaparib and olaparib plus durvalumab combination therapy and also to better understand the studied disease, breast cancer, and associated health problems. Olaparib is a type of drug called a PARP (poly [adenosine diphosphate-ribose] polymerase) inhibitor. PARP inhibitors can destroy cancer cells that are not good at repairing DNA damage. Olaparib is also approved by US Food and Drug Administration (FDA), European Medicines Agency (EMA) and in other countries for treating women with BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Durvalumab is a type of anticancer drug called immunotherapy that targets cancer cells by blocking the signal that prevents the immune system from seeing the cancer cell. Your immune system can then attack and kill the cancer cells. Durvalumab is approved by the FDA and the EMA for the treatment of patients with locally advanced non-small cell lung cancer after receiving chemoradiation therapy and extensive-stage small cell lung cancer in combination with chemotherapy. Some parts of this study are experimental, which means that durvalumab and the combination of olaparib and durvalumab are still in the development stage for the treatment of breast cancer, and they are not approved for treatment of breast cancer, except for use in research studies like this. |
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Detailed Description | The investigation of olaparib as monotherapy or olaparib in combination with durvalumab in patients with early stage BRCAm, oestrogen receptor (ER)-negative or ER-low, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who are candidates for neoadjuvant therapy supports the ongoing effort to identify novel agents and new drug combinations that can improve pathological complete response (pCR) rates and event-free survival (EFS). In patients at a lower risk (T1b-c/N0) of disease recurrence and a higher chance for cure, monotherapy olaparib may provide adequate neoadjuvant treatment. In contrast, monotherapy olaparib may be inadequate neoadjuvant treatment for those patients at a higher risk (T2/N0 or T1/N1) of recurrence, and the addition of an immune checkpoint inhibitor (ICI) to the neoadjuvant regimen may improve long-term outcomes as was seen in KEYNOTE-522 and GeparNuevo. However, the risk of irreversible immune-mediated adverse events (AEs) of the endocrine system due to ICI use supports the use of ICIs only in the cohort of patients at higher risk for disease recurrence. For both the lower and higher risk groups, the study treatments have the potential for the development of de-escalation strategies in this disease setting where traditional chemotherapy regimens may be avoided altogether. While assessment of the efficacy of the combination of olaparib and durvalumab is ongoing, there are sufficient safety data available to develop a safety and tolerability profile for the combination. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Intervention Model Description: There will be 2 cohorts: Cohort A will consist of a lower-risk population Cohort B will consist of a higher-risk population Participants will be allocated to receive 300 mg oral olaparib twice daily as monotherapy or in combination with durvalumab 1500 mg via intravenous infusion every 4 weeks for a minimum of 4 and a maximum of six 28-day cycles before undergoing definitive surgery. Each participant will undergo definitive surgery, preferably within 6 weeks after receiving the final dose of neoadjuvant olaparib therapy, followed by standard treatment (radiation therapy, systemic therapy per institutional standards). Participants who achieve pCR at surgery, will be allowed to continue on treatment with olaparib in the adjuvant setting in lieu of standard adjuvant systemic therapy, per physician's choice. If the physician chooses adjuvant olaparib, then the total duration of olaparib therapy in the neoadjuvant and adjuvant setting should be 12 cycles. Primary Purpose: Treatment |
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Condition ICMJE | Breast Cancer | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Active, not recruiting | ||||
Actual Enrollment ICMJE |
56 | ||||
Original Estimated Enrollment ICMJE |
80 | ||||
Estimated Study Completion Date ICMJE | December 31, 2026 | ||||
Estimated Primary Completion Date | May 2, 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 130 Years (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | Australia, Austria, Belgium, Germany, Israel, Italy, Spain, United Kingdom, United States | ||||
Removed Location Countries | France | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT05498155 | ||||
Other Study ID Numbers ICMJE | D931CC00001 2021-005231-22 ( EudraCT Number ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | AstraZeneca | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | AstraZeneca | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | AstraZeneca | ||||
Verification Date | May 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |