To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.

NCT03286842 | Completed Phase 3 Results FDA Drug

• 1 other identifier: D0816C00018
• Study Type: interventional
• Target: 256
• Locations: 15 countries
• Sites: 123

Brief 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.

Conditions

HER2-ve Metastatic Breast Cancer; Germline BRCA1/2 Mutations; Somatic BRCA1/2 Mutations

Keywords

HER2-ve metastatic breast cancer; Germline BRCA1/2 mutations; Somatic BRCA1/2 mutations; BRCA1; BRCA2

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  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

  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

  At every visit until second progression or death or end of study (up to 3 years)

Study Arms (1)

Olaparib

EXPERIMENTAL

Olaparib 150mg tablets administered orally twice daily continuously

Drug: Olaparib

Interventions

Olaparib DRUG

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.

Olaparib

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (123)

Research Site

Towson, Maryland, 21204, United States

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Jackson, Mississippi, 39202, United States

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Plovdiv, 4004, Bulgaria

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Sofia, 1303, Bulgaria

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Sofia, 1330, Bulgaria

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Varna, 9000, Bulgaria

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Vancouver, British Columbia, V5Z 4E6, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Québec, Quebec, G1S 4L8, Canada

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Angers, 49055, France

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Avignon, 84000, France

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Besançon, 25000, France

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Bordeaux, 33076, France

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Caen, 14076, France

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Le Mans, 72000, France

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Lille, 59000, France

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Limoges, 87042, France

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Lorient, 56322, France

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Marseille, 13273, France

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Montpellier, 34070, France

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Nancy, 54100, France

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Nantes, 44202, France

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Paris, 75475, France

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Paris, 75908, France

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Pierre-Bénite, 69495, France

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Plerin SUR MER, 22190, France

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Rennes, 35042, France

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Rouen, 76021, France

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Saint-Herblain, 44805, France

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Saint-Quentin, 02321, France

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Toulouse, 31059, France

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Cologne, 50931, Germany

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Dresden, 1307, Germany

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Erlangen, 91054, Germany

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Essen, 45130, Germany

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Essen, 45147, Germany

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Hanover, 30625, Germany

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München, 80637, Germany

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München, 81675, Germany

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Münster, 48149, Germany

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Rostock, 18059, Germany

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Budapest, 1032, Hungary

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Budapest, 1083, Hungary

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Aviano, 33081, Italy

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Bologna, 40138, Italy

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Candiolo, 10060, Italy

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Catania, 95122, Italy

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Genova, 16132, Italy

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Milan, 20132, Italy

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Napoli, 80131, Italy

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Padua, 35128, Italy

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Perugia, 06132, Italy

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Prato, 59100, Italy

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Roma, 00144, Italy

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Roma, 00161, Italy

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Roma, 00189, Italy

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Rozzano, 20089, Italy

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Nagoya, 464-8681, Japan

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Shinagawa-ku, 142-8666, Japan

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Suita-shi, 565-0871, Japan

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Gdansk, 80-214, Poland

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Gliwice, 44-101, Poland

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Grzepnica, 72-003, Poland

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Lublin, 20-090, Poland

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Poznan, 61-866, Poland

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Szczecin, 70-111, Poland

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Warsaw, 02-781, Poland

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Wroclaw, 53-413, Poland

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Irkutsk, 664035, Russia

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Kazan', 420029, Russia

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Moscow, 115478, Russia

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Omsk, 644013, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, 191014, Russia

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Saint Petersburg, 197758, Russia

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Samara, 443031, Russia

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Surgut, 628408, Russia

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Ufa, 450054, Russia

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Daegu, 41404, South Korea

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Goyang-si, 10408, South Korea

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Incheon, 21565, South Korea

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Seongnam, 13620, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 135-710, South Korea

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Alicante, 03550, Spain

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Barcelona, 08036, Spain

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Cáceres, 10003, Spain

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Granada, 18014, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Madrid, 08035, Spain

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Madrid, 28040, Spain

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Madrid, 28050, Spain

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Majadahonda, 28222, Spain

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Pamplona, 31008, Spain

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San Cristóbal de La Laguna, 38320, Spain

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Seville, 41009, Spain

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Seville, 41013, Spain

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Vigo, 36312, Spain

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Zaragoza, 50009, Spain

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Kaohsiung City, 80756, Taiwan

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Taichung, 40447, Taiwan

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Taipei, 10048, Taiwan

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Taipei, 11217, Taiwan

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Taoyuan, 333, Taiwan

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Adana, 01120, Turkey (Türkiye)

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Adana, 01130, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Istanbul, 34390, Turkey (Türkiye)

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Izmir, 35575, Turkey (Türkiye)

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Kayseri, 38039, Turkey (Türkiye)

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Konya, 42080, Turkey (Türkiye)

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Mersin, 33343, Turkey (Türkiye)

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Tekirdağ, 59100, Turkey (Türkiye)

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Cardiff, CF14 2TL, United Kingdom

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Colchester, CO4 5JL, United Kingdom

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Edinburgh, EH4 2XR, United Kingdom

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Glasgow, G12 0YN, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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London, SE1 9RT, United Kingdom

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London, SW3 6JJ, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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Related Publications (2)

• 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.

  PMID: 38112922 DERIVED

• Gelmon 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.

  PMID: 34087573 DERIVED

Related Links

• CSP\_redacted
• SAP\_redacted
• Related Info

MeSH Terms

Interventions

olaparib

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Karen Gelmon, MD, FRCPC

  BritishColumbiaCancerAgency, 600W.10th Ave,Vancouver,Canada.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: September 19, 2017
• Study Start: January 17, 2018
• Primary Completion: October 8, 2021
• Study Completion: October 8, 2021
• Last Updated: January 17, 2023
• Results First Posted: January 17, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

HU (2); GB (9); TU (9); BU (4); KR (7); FR (22); CA (3); US (2); JP (3); DE (10); IT (14); RU (10); ES (15); TW (5); PL (8)