HER2-ve Metastatic Breast CancerPhase 3NCT03286842
To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.
A Phase 3 study testing Olaparib in people with HER2-ve Metastatic Breast Cancer and Germline BRCA1/2 Mutations, run by AstraZeneca at 123 sites in 15 countries.
Trial summary
This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve metastatic breast cancer associated with germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- HER2-ve Metastatic Breast Cancer, Germline BRCA1/2 Mutations, Somatic BRCA1/2 Mutations
- What is being tested?
- Olaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 256 participants
- Where
- 123 sitesin 15 countries
- Study dates
- 17 Jan 2018to 8 Oct 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures. For patients aged <20 years and screened in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
- Patients must be ≥18 years of age.
- Histologically or cytologically confirmed HER2-ve breast cancer with evidence of metastatic disease. Patients can have either TNBC (defined as oestrogen receptor and progesterone receptor negative [immunohistochemistry nuclear staining <1%] and HER2-ve [immunohistochemistry 0, 1+ or 2+ and/or in situ hybridization nonamplified with ratio less than 2.0]) or oestrogen receptor / progesterone receptor positive breast cancer as long as they are HER2-ve.
- Documented BRCA1/2 status
- To be regarded as BRCA1/2 (+ve), the patient must have a mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function). Mutations that are not clearly pathogenic may be assessed by a committee of genetic specialists to adjudicate if the patient is eligible.
- Patients with tBRCA mutations: must be confirmed by a validated method (e.g. results from a CLIA-certified laboratory or CE-IVD device)
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- Prior treatment with a taxane or an anthracycline in either an adjuvant (may include neoadjuvant) or metastatic breast cancer treatment setting.
- Patients should have received no more than two prior cytotoxic chemotherapy regimens in the metastatic setting. If a patient has oestrogen receptor and/or progesterone receptor positive HER2 negative metastatic breast cancer and has completed a prior line of hormonal treatment, then if the current or currently planned choice of treatment for the patient does not include a hormonal treatment then they would be a suitable patient to enter the study. Previous endocrine therapy could be in either an adjuvant or a metastatic setting and include endocrine therapy in combination with a targeted agent such as a CDK4/6 or mTOR inhibitor.
- Be considered suitable, by the Investigator, for further treatment with single-agent chemotherapy for the metastatic disease
- Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below:
- Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless the patient has documented Gilbert's Syndrome
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase (SGPT)) ≤ 2.5 x institutional ULN unless liver metastases are present in which case they must be ≤ 5x ULN
- Patients must have creatinine clearance (CrCl) estimated using the Cockcroft- Gault equation of ≥ 51 mL/min or 24 hour urine test may be done if standard of care:
- Estimated CrCl = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72
- a- where F=0.85 for females and F=1 for males
- Patients must have a life expectancy ≥ 16 weeks
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1
- Postmenopausal is defined as (at least one criterion met):
- amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
- luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range for women under 50
- radiation-induced oophorectomy with last menses >1 year ago
- chemotherapy-induced menopause with >1 year interval since last menses
- surgical sterilisation (bilateral oophorectomy or hysterectomy).
- Women of childbearing potential, who are sexually active, must agree to the use of one highly effective form of contraception and their male partners must use a condom from the signing of the informed consent, throughout the period of taking study treatment and for at least 1 month after last dose of study drug, or they must totally/truly abstain from any form of sexual intercourse.
- Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use one highly effective form of contraception if they are of childbearing potential.
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations for greater than 6 months.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous enrolment in the present study
- Exposure to an investigational product (IP) during the last 1 month or 5 half-lives (whichever is longer) prior to enrolment
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
- Any previous treatment with a PARP inhibitor, including olaparib
- Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
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- Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
- Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
- Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
- Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML
- Patients with symptomatic uncontrolled brain metastases.
- Exception: Patients with adequately treated brain metastases documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids (except ≤10 mg/day prednisone or equivalent for at least 14 continuous days prior to dosing) for management of CNS symptoms are eligible, provided that a repeat CT or MRI following the identification of CNS metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases.
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
- Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
- Breastfeeding women
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product
- Patients with known active hepatitis (i.e., hepatitis B or C)
- Whole blood transfusions in the last 28 days prior to entry to the study.
Trial locations and contacts
123 sites in 15 countries.
123 sites in 15 countries
France22 sites
Research Site
Angers, 49055
Research Site
Avignon, 84000
Research Site
Besançon, 25000
Research Site
Bordeaux, 33076
Research Site
Caen, 14076
Research Site
Le Mans, 72000
Research Site
Lille, 59000
Research Site
Limoges, 87042
Research Site
Lorient, 56322
Research Site
Marseille, 13273
Research Site
Montpellier, 34070
Research Site
Nancy, 54100
Research Site
Nantes, 44202
Research Site
Paris, 75475
Research Site
Paris, 75908
Research Site
Pierre-Bénite, 69495
Research Site
Plerin SUR MER, 22190
Research Site
Rennes, 35042
Research Site
Rouen, 76021
Research Site
Saint-Herblain, 44805
Research Site
Saint-Quentin, 02321
Research Site
Toulouse, 31059
Spain15 sites
Research Site
Alicante, 03550
Research Site
Barcelona, 08036
Research Site
Cáceres, 10003
Research Site
Granada, 18014
Research Site
L'Hospitalet de Llobregat, 08907
Research Site
Madrid, 08035
Research Site
Madrid, 28040
Research Site
Madrid, 28050
Research Site
Majadahonda, 28222
Research Site
Pamplona, 31008
Research Site
San Cristóbal de La Laguna, 38320
Research Site
Seville, 41009
Research Site
Seville, 41013
Research Site
Vigo, 36312
Research Site
Zaragoza, 50009
Italy14 sites
Research Site
Aviano, 33081
Research Site
Bologna, 40138
Research Site
Candiolo, 10060
Research Site
Catania, 95122
Research Site
Genova, 16132
Research Site
Milan, 20132
Research Site
Naples, 80131
Research Site
Padova, 35128
Research Site
Perugia, 06132
Research Site
Prato, 59100
Research Site
Roma, 00144
Research Site
Roma, 00161
Research Site
Roma, 00189
Research Site
Rozzano, 20089
Germany10 sites
Research Site
Cologne, 50931
Research Site
Dresden, 1307
Research Site
Erlangen, 91054
Research Site
Essen, 45130
Research Site
Essen, 45147
Research Site
Hanover, 30625
Research Site
München, 80637
Research Site
München, 81675
Research Site
Münster, 48149
Research Site
Rostock, 18059
Russia10 sites
Research Site
Irkutsk, 664035
Research Site
Kazan', 420029
Research Site
Moscow, 115478
Research Site
Omsk, 644013
Research Site
Ryazan, 390011
Research Site
Saint Petersburg, 191014
Research Site
Saint Petersburg, 197758
Research Site
Samara, 443031
Research Site
Surgut, 628408
Research Site
Ufa, 450054
Turkey (Türkiye)9 sites
Research Site
Adana, 01120
Research Site
Adana, 01130
Research Site
Ankara, 06230
Research Site
Istanbul, 34390
Research Site
Izmir, 35575
Research Site
Kayseri, 38039
Research Site
Konya, 42080
Research Site
Mersin, 33343
Research Site
Tekirdağ, 59100
United Kingdom9 sites
Research Site
Cardiff, CF14 2TL
Research Site
Colchester, CO4 5JL
Research Site
Edinburgh, EH4 2XR
Research Site
Glasgow, G12 0YN
Research Site
Leeds, LS9 7TF
Research Site
London, SE1 9RT
Research Site
London, SW3 6JJ
Research Site
Manchester, M20 4BX
Research Site
Sutton, SM2 5PT
Poland8 sites
Research Site
Gdansk, 80-214
Research Site
Gliwice, 44-101
Research Site
Grzepnica, 72-003
Research Site
Lublin, 20-090
Research Site
Poznan, 61-866
Research Site
Szczecin, 70-111
Research Site
Warsaw, 02-781
Research Site
Wroclaw, 53-413
South Korea7 sites
Research Site
Daegu, 41404
Research Site
Goyang-si, 10408
Research Site
Incheon, 21565
Research Site
Seongnam, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 135-710
Taiwan5 sites
Research Site
Kaohsiung City, 80756
Research Site
Taichung, 40447
Research Site
Taipei, 10048
Research Site
Taipei, 11217
Research Site
Taoyuan City, 333
Bulgaria4 sites
Research Site
Plovdiv, 4004
Research Site
Sofia, 1303
Research Site
Sofia, 1330
Research Site
Varna, 9000
Canada3 sites
Research Site
Québec, Quebec, G1S 4L8
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Vancouver, British Columbia, V5Z 4E6
Japan3 sites
Research Site
Nagoya, 464-8681
Research Site
Shinagawa-ku, 142-8666
Research Site
Suita-shi, 565-0871
United States2 sites
Research Site
Jackson, Mississippi, 39202
Research Site
Towson, Maryland, 21204
About this study
Official title: A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Monotherapy in the Treatment of HER2-ve Metastatic Breast Cancer Patients With Germline or Somatic BRCA1/2 Mutations.
This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve metastatic breast cancer associated with germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations.
Read the detailed description
The study is a phase IIIb, multicenter, single-arm, open-label study designed to evaluate the clinical effectiveness in a real-world setting of olaparib monotherapy in patients with confirmed germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations. This study will generate additional data to support other olaparib studies, which may help inform and guide clinical practice. Physician defined the progression-free survival (PFS) for gBRCAm patients is the primary outcome measure. Based on the prevalence of gBRCA1/2 mutations, it is estimated that up to 1400 patients may require screening in order to identify 250 gBRCA mutated patients and 20 sBRCA mutated patients. Patients will be administered two olaparib 150mg tablets in morning and evening of every day after a light meal. Dose reductions may be required for olaparib treatment related toxicities. Patients should continue to receive study treatment until documented physician-defined disease progression as assessed by the investigator (gBRCA mutated patients), RECIST1.1 disease progression (sBRCA mutated patients) or unacceptable toxicity, or for as long as they do not meet any other discontinuation criteria. A positive benefit/risk profile is expected and no ethical issues are identified from exposing patients to olaparib within the planned clinical study.
- Being tested
- Olaparib
- Keywords
- HER2-ve metastatic breast cancer, Germline BRCA1/2 mutations, Somatic BRCA1/2 mutations, BRCA1, BRCA2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Patients will be administered olaparib orally, twice daily at 300 mg. Two (2) 150 mg olaparib tablets should be taken at the same time each morning and evening of every day, approximately 12 hours apart.
| Study group | Role | What they receive |
|---|---|---|
| Olaparib | Experimental | Olaparib 150mg tablets administered orally twice daily continuously Receives: Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.
Measured: At every visit until the earliest of disease progression, death or end of study (up to 3 years)
Secondary outcomes (8)
Overall Survival (OS) in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of overall survival in germline BRCA mutated participants was determined. OS is defined as the time from first dose of olaparib to the date of death from any cause.
Measured: At every visit and until death or end of study (up to 3 years)
Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TFST is defined as the time from first dose of olaparib to first subsequent treatment commencement or death if this occurs before commencement of first subsequent treatment.
Measured: At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)
Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. TSST is defined as the time from first dose of olaparib to second subsequent treatment commencement or death if this occurs before commencement of second subsequent treatment.
Measured: At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)
Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated patients was determined. TDT is defined as the time from first dose of olaparib to study treatment discontinuation or death if this occurs before discontinuation of study treatment.
Measured: At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)
Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of time to use of subsequent therapies, second progression, and study treatment discontinuation in germline BRCA mutated participants was determined. PFS2 is defined as the time from first dose of olaparib to the earliest progression event subsequent to that used for the primary variable PFS or death from any cause. Patients alive and for whom a second disease progression has not been observed will be censored at the last time known to be alive and without a second disease progression. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented
Measured: At every visit until second progression or death or end of study (up to 3 years)
Clinical Response Rate (CRR) in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. CRR is defined as the percentage of patients assessed by the Investigator as responding. Response in gBRCAm patients were based on the Investigator's assessment. Data obtained up until progression, or last evaluable assessment in the absence of progression, will be included in the assessment of CRR. However, any responses, which occurred after a further anticancer therapy was received, will not be included in the numerator for the CRR calculation.
Measured: At every visit until disease progression or death or end of study (up to 3 years)
Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting by assessment of clinical response rate and duration of clinical response in germline BRCA mutated participants was determined. DoCR is defined as the time from the date the Investigator first assessed the patient as responding to the date the Investigator assessed the patient as progressing or the date of death from any cause. The end of response should coincide with the date of progression or death used for the PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit response. If a patient does not progress following a response, they will be censored at the PFS censoring date.
Measured: At every visit until disease progression or death or end of study (up to 3 years)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
The safety and tolerability of olaparib treatment in HER2-ve metastatic breast cancer patients in a real-word setting was evaluated.
Measured: From Screening (Day -28 to Day -1) until post DCO [up to 3 years]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2017
- Study start17 Jan 2018
- Primary completion8 Oct 2021
- Study completion8 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HER2-ve Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 256 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Karen Gelmon, MD, FRCPC, Principal investigator, BritishColumbiaCancerAgency, 600W.10th Ave,Vancouver,Canada.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03286842
- Sponsor's protocol ID
- D0816C00018
- Status last verified
- Nov 2022
- First submitted
- 17 Aug 2017
- Last updated
- 17 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Balmana J, Fasching PA, Couch FJ, Delaloge S, Labidi-Galy I, O'Shaughnessy J, Park YH, Eisen AF, You B, Bourgeois H, Goncalves A, Kemp Z, Swampillai A, Jankowski T, Sohn JH, Poddubskaya E, Mukhametshina G, Aksoy S, Timcheva CV, Park-Simon TW, Anton-Torres A, John E, Baria K, Gibson I, Gelmon KA; LUCY investigators. Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY. Breast Cancer Res Treat. 2024 Apr;204(2):237-248. doi: 10.1007/s10549-023-07165-x. Epub 2023 Dec 19.
PubMed 38112922Gelmon KA, Fasching PA, Couch FJ, Balmana J, Delaloge S, Labidi-Galy I, Bennett J, McCutcheon S, Walker G, O'Shaughnessy J; Collaborating Investigators. Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis. Eur J Cancer. 2021 Jul;152:68-77. doi: 10.1016/j.ejca.2021.03.029. Epub 2021 Jun 1.
PubMed 34087573
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Monotherapy in the Treatment of HER2-ve Metastatic Breast Cancer Patients With Germline or Somatic BRCA1/2 Mutations.
- ClinicalTrials.gov ID
- NCT03286842
- Acronym / sponsor ID
- D0816C00018
- Keywords
- HER2-ve metastatic breast cancer, Germline BRCA1/2 mutations, Somatic BRCA1/2 mutations, BRCA1, BRCA2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 256 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 17 Jan 2018 (actual)
- Primary completion
- 8 Oct 2021 (actual)
- Study completion
- 8 Oct 2021 (actual)
- First posted
- 19 Sep 2017 (actual)
- Results
- Posted 17 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve metastatic breast cancer associated with germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations.
Detailed description
The study is a phase IIIb, multicenter, single-arm, open-label study designed to evaluate the clinical effectiveness in a real-world setting of olaparib monotherapy in patients with confirmed germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations. This study will generate additional data to support other olaparib studies, which may help inform and guide clinical practice. Physician defined the progression-free survival (PFS) for gBRCAm patients is the primary outcome measure. Based on the prevalence of gBRCA1/2 mutations, it is estimated that up to 1400 patients may require screening in order to identify 250 gBRCA mutated patients and 20 sBRCA mutated patients. Patients will be administered two olaparib 150mg tablets in morning and evening of every day after a light meal. Dose reductions may be required for olaparib treatment related toxicities. Patients should continue to receive study treatment until documented physician-defined disease progression as assessed by the investigator (gBRCA mutated patients), RECIST1.1 disease progression (sBRCA mutated patients) or unacceptable toxicity, or for as long as they do not meet any other discontinuation criteria. A positive benefit/risk profile is expected and no ethical issues are identified from exposing patients to olaparib within the planned clinical study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib | Experimental | Drug: OlaparibOlaparib 150mg tablets administered orally twice daily continuously |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Provision of informed consent prior to any study specific procedures. For patients aged <20 years and screened in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
- Patients must be ≥18 years of age.
- Histologically or cytologically confirmed HER2-ve breast cancer with evidence of metastatic disease. Patients can have either TNBC (defined as oestrogen receptor and progesterone receptor negative [immunohistochemistry nuclear staining <1%] and HER2-ve [immunohistochemistry 0, 1+ or 2+ and/or in situ hybridization nonamplified with ratio less than 2.0]) or oestrogen receptor / progesterone receptor positive breast cancer as long as they are HER2-ve.
- Documented BRCA1/2 status
- Prior treatment with a taxane or an anthracycline in either an adjuvant (may include neoadjuvant) or metastatic breast cancer treatment setting.
Key exclusion criteria (22 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Previous enrolment in the present study
- Exposure to an investigational product (IP) during the last 1 month or 5 half-lives (whichever is longer) prior to enrolment
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
- Any previous treatment with a PARP inhibitor, including olaparib
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaparibPatients will be administered olaparib orally, twice daily at 300 mg. Two (2) 150 mg olaparib tablets should be taken at the same time each morning and evening of every day, approximately 12 hours apart. | Drug | Olaparib |
Primary outcome
Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants
Time frame: At every visit until the earliest of disease progression, death or end of study (up to 3 years)
The clinical effectiveness of olaparib treatment in HER2-ve metastatic breast cancer participants in a real-world setting through assessment of PFS in germline BRCA mutated patients was evaluated. PFS is defined as the time from first dose of olaparib to the date of progression or death from any cause. In this study, disease progression in gBRCAm patients will be based on Investigator assessment, i.e. radiological ( e.g. RECIST) progression, symptomatic progression, or clear progression of non-measurable disease, as long as progression can be documented.
8 secondary outcomes
Overall Survival (OS) in Germline BRCA Mutated Participants
Time frame: At every visit and until death or end of study (up to 3 years)
Time to First Subsequent Treatment or Death (TFST) in Germline BRCA Mutated Participants
Time frame: At every visit until start of first subsequent anticancer treatment or death or end of study (up to 3 years)
Time to Second Subsequent Treatment or Death (TSST) in Germline BRCA Mutated Participants
Time frame: At every visit until start of second subsequent anticancer treatment or death or end of study (up to 3 years)
Time to Study Treatment Discontinuation or Death (TDT) in Germline BRCA Mutated Participants
Time frame: At every visit and until discontinuation of study treatment or death or end of study (up to 3 years)
Time to Second Progression or Death (PFS2) in Germline BRCA Mutated Participants
Time frame: At every visit until second progression or death or end of study (up to 3 years)
Clinical Response Rate (CRR) in Germline BRCA Mutated Participants
Time frame: At every visit until disease progression or death or end of study (up to 3 years)
Duration of Clinical Response (DoCR) in Germline BRCA Mutated Participants
Time frame: At every visit until disease progression or death or end of study (up to 3 years)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Screening (Day -28 to Day -1) until post DCO [up to 3 years]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38112922Balmana J, Fasching PA, Couch FJ, Delaloge S, Labidi-Galy I, O'Shaughnessy J, Park YH, Eisen AF, You B, Bourgeois H, Goncalves A, Kemp Z, Swampillai A, Jankowski T, Sohn JH, Poddubskaya E, Mukhametshina G, Aksoy S, Timcheva CV, Park-Simon TW, Anton-Torres A, John E, Baria K, Gibson I, Gelmon KA; LUCY investigators. Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: final analysis of LUCY. Breast Cancer Res Treat. 2024 Apr;204(2):237-248. doi: 10.1007/s10549-023-07165-x. Epub 2023 Dec 19.
- Derived from this study: PubMed 34087573Gelmon KA, Fasching PA, Couch FJ, Balmana J, Delaloge S, Labidi-Galy I, Bennett J, McCutcheon S, Walker G, O'Shaughnessy J; Collaborating Investigators. Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis. Eur J Cancer. 2021 Jul;152:68-77. doi: 10.1016/j.ejca.2021.03.029. Epub 2021 Jun 1.
- CSP\_redactedLink provided by the sponsor.
- SAP\_redactedLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen Gelmon, MD, FRCPC principal investigator
BritishColumbiaCancerAgency, 600W.10th Ave,Vancouver,Canada.
123 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Olaparib in people with HER2-ve Metastatic Breast Cancer and Germline BRCA1/2 Mutations, run by AstraZeneca at 123 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 123 sites in France, Spain, Italy, Germany, Russia and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants (time frame: At every visit until the earliest of disease progression, death or end of study (up to 3 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03286842, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2023.