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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05498155




Registration number
NCT05498155
Ethics application status
Date submitted
5/07/2022
Date registered
11/08/2022
Date last updated
30/10/2024

Titles & IDs
Public title
Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer
Scientific title
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
Secondary ID [1] 0 0
2021-005231-22
Secondary ID [2] 0 0
D931CC00001
Universal Trial Number (UTN)
Trial acronym
OlympiaN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Neoadjuvant Olaparib monotherapy group
Other interventions - Neoadjuvant combination therapy with olaparib plus durvalumab

Experimental: Cohort A - Cohort A will consist of a lower-risk population of participants with HER2-negative ER-negative or ER-low defined as having a tumour size \>5 mm and =20 mm and N0 (T1b-c/N0).

Experimental: Cohort B - Cohort B will consist of a higher-risk population of participants with HER2-negative ER-negative or ER-low defined as having a tumour size of \>20 mm but =50 mm and N0 (T2/N0), or having a tumour size of \>1 mm but =20 mm and N1 (T1/N1).


Treatment: Drugs: Neoadjuvant Olaparib monotherapy group
Neoadjuvant olaparib monotherapy (300 mg BID) for four to six 28-day cycles.

Other interventions: Neoadjuvant combination therapy with olaparib plus durvalumab
Neoadjuvant combination therapy with olaparib (300 mg BID) plus durvalumab (1500 mg IV Q4W) for four to six 28-day cycles.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Approx. 4 to 6 months
Secondary outcome [1] 0 0
To evaluate the efficacy, measured by pCR rate, of olaparib monotherapy and olaparib plus durvalumab combination therapy as assessed by local pathology review
Timepoint [1] 0 0
Approx. 4 to 6 months
Secondary outcome [2] 0 0
To evaluate the efficacy, measured by RCB (residual cancer burden), of olaparib monotherapy and olaparib plus durvalumab combination therapy as assessed by central pathology review
Timepoint [2] 0 0
Approx. 4 to 6 months
Secondary outcome [3] 0 0
To evaluate the efficacy, measured by RCB, of olaparib monotherapy and olaparib plus durvalumab combination therapy as assessed by local pathology review
Timepoint [3] 0 0
Approx. 4 to 6 months
Secondary outcome [4] 0 0
To evaluate the efficacy of olaparib monotherapy and olaparib plus durvalumab combination therapy in terms of change from baseline tumour volume. Tumour volume will be assessed by local radiology review.
Timepoint [4] 0 0
Approx. 4 to 6 months
Secondary outcome [5] 0 0
To evaluate the efficacy of olaparib monotherapy and olaparib plus durvalumab combination therapy in terms of change from baseline tumour volume. Tumour volume will be assessed by local radiology review.
Timepoint [5] 0 0
Approx. 4 to 6 months
Secondary outcome [6] 0 0
To evaluate the efficacy of olaparib monotherapy and olaparib plus durvalumab combination therapy by assessment of EFS (event-free survival).
Timepoint [6] 0 0
Approx. 3 years
Secondary outcome [7] 0 0
Safety and tolerability profile of olaparib monotherapy and olaparib plus durvalumab combination therapy by assessment of advers events and seriuos advers events (AEs/SAEs)
Timepoint [7] 0 0
Through study completion, around 15 months for single patient
Secondary outcome [8] 0 0
The number of participants with adverse events /serious adverse events of olaparib monotherapy and olaparib plus durvalumab combination therapy.
Timepoint [8] 0 0
Through study completion, around 15 months for single patient
Secondary outcome [9] 0 0
Safety and tolerability profile of olaparib monotherapy when given as adjuvant therapy to participants who achieve pCR by assessment of AEs/SAEs
Timepoint [9] 0 0
Through study completion, around 15 months for single patient
Secondary outcome [10] 0 0
The number of participants with adverse events / serious adverse events of olaparib monotherapy when given as adjuvant therapy to participants who achieve pCR.
Timepoint [10] 0 0
Through study completion, around 15 months for single patient
Secondary outcome [11] 0 0
Systolic blood pressure (SBP), diastolic blood pressure (DBP)
Timepoint [11] 0 0
Through study completion, around 15 months for single patient
Secondary outcome [12] 0 0
Body Temperature
Timepoint [12] 0 0
Through study completion, around 15 months for single patient
Secondary outcome [13] 0 0
Pulse rate (heart rate)
Timepoint [13] 0 0
Through study completion, around 15 months for single patient
Secondary outcome [14] 0 0
Weight
Timepoint [14] 0 0
Through study completion, around 15 months for single patient

Eligibility
Key inclusion criteria
* Males or Females =18 years
* Minimum body weight of 30 kg
* Capable of giving signed informed consent.
* Male and Female participants of childbearing potential must use effective methods of contraception
* Histologically confirmed, newly diagnosed, primary, operable, nonmetastatic invasive breast cancer with the following characteristics:

--ER-negative or ER-low defined as IHC nuclear staining =10%
* HER2-negative (not eligible for anti-HER2 therapy) defined as:

* IHC 0, 1+ without in situ hybridization OR
* In situ hybridization non-amplified with ratio less than 2.0 OR
* In situ hybridization average HER2 copy number < 6 signals/cells
* Clinical TNM staging (per AJCC 8th Edition) as follows:

* T1b (>5 mm but =10 mm), N0, no known metastases (M0 or MX); OR
* T1c (>10 mm but =20 mm), N0, no known metastases (M0 or MX); OR
* T1 (>1 mm but =20 mm), N1, no known metastases (M0 or MX); OR
* T2 (>20 mm but =50 mm), N0, no known metastases (M0 or MX).).
* Documented deleterious or suspected deleterious mutation in BRCA1 or BRCA2 from local BRCA testing using either a germline or tumour test.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants must have adequate organ and bone marrow function
* Participant must be willing to undergo a baseline research biopsy prior to start of study treatment.
* Participant must be willing to have any leftover tumour tissue/FFPE from the diagnostic biopsy submitted for research purposes, if available.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any evidence of other diseases (such as severe or uncontrolled systemic diseases or active, uncontrolled infections, including but not limited to, uncontrolled ventricular arrhythmia, uncontrolled hypertension, recent [within 3 months] myocardial infarction, uncontrolled major seizure disorder, renal transplant, active bleeding diseases, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan
* Refractory nausea and vomiting, chronic gastrointestinal disease likely to interfere with absorption of the study medication, inability to swallow the formulated product
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease for =5 years before the first dose of study intervention and of low potential risk for recurrence
* Participants with MDS or AML
* For higher risk (Cohort B) participants only: Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc), autoimmune pneumonitis, and autoimmune myocarditis
* Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody
* Known to have tested positive for human immunodeficiency virus unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months
* History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
* Participant must not have had any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation, or experimental therapy
* For higher risk (Cohort B) participants only: Prior exposure to anti-PD1, anti-PD-L1, or anti-CTLA4 agents (ICIs); OR an agent directed to other co-inhibitory or co-stimulatory T-cell receptors
* Any concurrent anticancer treatment
* Major surgical procedure (excluding placement of vascular access, local surgery of isolated lesions, or diagnostic staging) within 2 weeks of the first dose of study intervention
* For higher risk (Cohort B) participants only: Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
* Concomitant use of:

* Known strong cytochrome P450 (CYP3A) inhibitors or moderate CYP3A inhibitors within 2 weeks prior to first dose of study intervention
* Known strong CYP3A inducers or moderate CYP3A inducers .The required washout period prior to starting study therapy is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
Austria
State/province [6] 0 0
Rankweil
Country [7] 0 0
Austria
State/province [7] 0 0
Salzburg
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Liège
Country [10] 0 0
Germany
State/province [10] 0 0
Augsburg, BY
Country [11] 0 0
Germany
State/province [11] 0 0
Düsseldorf
Country [12] 0 0
Germany
State/province [12] 0 0
Essen
Country [13] 0 0
Germany
State/province [13] 0 0
Hamburg
Country [14] 0 0
Germany
State/province [14] 0 0
Hannover
Country [15] 0 0
Germany
State/province [15] 0 0
Heidelberg
Country [16] 0 0
Germany
State/province [16] 0 0
Köln
Country [17] 0 0
Germany
State/province [17] 0 0
Muenster
Country [18] 0 0
Germany
State/province [18] 0 0
Munchen
Country [19] 0 0
Israel
State/province [19] 0 0
Jerusalem
Country [20] 0 0
Israel
State/province [20] 0 0
Kfar Saba
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Israel
State/province [22] 0 0
Rehovot
Country [23] 0 0
Israel
State/province [23] 0 0
Tel Aviv
Country [24] 0 0
Italy
State/province [24] 0 0
Bologna
Country [25] 0 0
Italy
State/province [25] 0 0
Meldola
Country [26] 0 0
Italy
State/province [26] 0 0
Modena
Country [27] 0 0
Italy
State/province [27] 0 0
Roma
Country [28] 0 0
Italy
State/province [28] 0 0
Rozzano
Country [29] 0 0
Spain
State/province [29] 0 0
A Coruña
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Caceres
Country [32] 0 0
Spain
State/province [32] 0 0
Hospitalet deLlobregat
Country [33] 0 0
Spain
State/province [33] 0 0
Lérida
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Malaga
Country [36] 0 0
Spain
State/province [36] 0 0
Sevilla
Country [37] 0 0
Spain
State/province [37] 0 0
Valencia
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05498155
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anitra Fielding, MBChB
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05498155