Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.

Breast Cancer Metastatic Clinical Trial

— OlympiAD  

Official title:

A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02000622
• Other study ID #: D0819C00003
• Secondary ID: 2013-005137-20
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 27, 2014
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open label, randomised, controlled, multi-centre phase III study will assess the efficacy and safety of single agent olaparib vs standard of care based on physician's choice of capecitabine, vinorelbine or eribulin in metastatic breast cancer patients with gBRCA 1/2 mutations.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 302
• Est. completion date: December 31, 2024
• Est. primary completion date: December 9, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious.
• Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
• Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting.
• Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study entry elapsed.
• ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.
• ECOG performance status 0-1.
• Adequate bone marrow, kidney and liver function.

Exclusion Criteria:

• Prior treatment with PARP inhibitor.
• Patients with HER2 positive disease.
• More than 2 prior lines of chemotherapy for metastatic breast cancer.
• Untreated and/or uncontrolled brain metastases.
• Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed.
• Known HIV (Human Immunodeficiency Virus) infection.
• Pregnant or breast-feeding women.

Related Conditions & MeSH terms

• BRCA 1 Gene Mutation
• BRCA 2 Gene Mutation
• Breast Cancer Metastatic
• Breast Neoplasms

Intervention

Drug:
• Olaparib
Patients will be administered olaparib orally twice daily (bid) at 300 mg. Two (2) x 150 mg olaparib tablets should be taken at the same times each morning and evening of each day, approximately 12 hours apart with approximately 240 mL of water.
• Physician's choice chemotherapy
Investigators will declare one of the following regimens: Capecitabine 2500 mg/m2 po daily (divided in 2 doses) x 14 days, repeat every 21 days Vinorelbine 30 mg/m2 IV Day 1 and Day 8, repeat every 21 days Eribulin 1.4 mg/m2 IV Day 1 and Day 8, repeat every 21 days

Locations

Country	Name	City	State
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Varna
Bulgaria	Research Site	Vratza
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Dalian
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
Czechia	Research Site	Brno
Czechia	Research Site	Olomouc
Czechia	Research Site	Praha 2
France	Research Site	Caen Cedex
France	Research Site	Montpellier
France	Research Site	Rouen
France	Research Site	Strasbourg Cedex
France	Research Site	Villejuif
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Veszprém
Italy	Research Site	Bologna
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osaka-city
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Suita-city
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Estado de México
Mexico	Research Site	Merida
Mexico	Research Site	Merida
Mexico	Research Site	Mérida
Mexico	Research Site	Mexico
Mexico	Research Site	San Juan del Rio
Peru	Research Site	Cusco
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	San Borja
Poland	Research Site	Elblag
Poland	Research Site	Gdansk
Poland	Research Site	Grzepnica
Poland	Research Site	Lódz
Poland	Research Site	Tarnobrzeg
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Cluj Napoca
Romania	Research Site	Cluj-Napoca
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saransk
Russian Federation	Research Site	St-Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Yaroslavl
Spain	Research Site	Barcelona
Spain	Research Site	Córdoba
Spain	Research Site	Granada
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Oviedo
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Switzerland	Research Site	Bern
Switzerland	Research Site	Lausanne
Switzerland	Research Site	Zürich
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Gaziantep
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Kayseri
Turkey	Research Site	Konya
Turkey	Research Site	Mersin
United Kingdom	Research Site	Aberdeen
United Kingdom	Research Site	Colchester
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Plymouth
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Burlington	Vermont
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbia	Missouri
United States	Research Site	Columbus	Georgia
United States	Research Site	Commack	New York
United States	Research Site	Denver	Colorado
United States	Research Site	Detroit	Michigan
United States	Research Site	Germantown	Tennessee
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Harrison	New York
United States	Research Site	Houston	Texas
United States	Research Site	Jackson	Mississippi
United States	Research Site	Jacksonville	Florida
United States	Research Site	Lafayette	Louisiana
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Marietta	Georgia
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Niles	Illinois
United States	Research Site	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Plantation	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Rochester	Minnesota
United States	Research Site	Rockville Centre	New York
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Louis Park	Minnesota
United States	Research Site	San Diego	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Sayre	Pennsylvania
United States	Research Site	Syracuse	New York
United States	Research Site	Tyler	Texas
United States	Research Site	Washington	District of Columbia
United States	Research Site	Whittier	California
United States	Research Site	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
AstraZeneca	Merck Sharp & Dohme LLC, Myriad Genetic Laboratories, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  China,  Czechia,  France,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to First Subsequent Cancer Therapy or Death (TFST)	Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.	Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
Other	Time to Second Subsequent Cancer Therapy or Death (TSST)	Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.	Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
Other	Time to First Subsequent Cancer Therapy or Death (TFST) at Extended OS	Time from randomisation to the earliest of first subsequent cancer therapy start date following study treatment discontinuation, or death.	Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.
Other	Time to Second Subsequent Cancer Therapy or Death (TSST) at Extended OS	Time from randomisation to the earliest of second subsequent cancer therapy start date following study treatment discontinuation, or death.	Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.
Primary	Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)	Time from randomisation to the earliest of objective radiological progression or death by any cause in the absence of objective progression. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Secondary	Time to Second Progression or Death (PFS2)	Time from randomisation to the earliest of the progression event subsequent to the first objective radiological progression, or death. Second progression may involve any of; objective radiological or symptomatic progression or death. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Symptomatic progression is assessed by investigators based on clinical examination.	Second progression status reviewed every 8 weeks following the first objective radiological progression as per investigator assessment. Assessed up to a maximum of 30 months.
Secondary	Overall Survival (OS)	Time from randomisation until death due to any cause.	Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 30 months.
Secondary	Objective Response Rate (ORR) Using Blinded Independent Central Review (BICR) Data Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)	Number of responders according to blinded independent central review (BICR) assessment. Per Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions; Overall Response = CR + PR.	Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Secondary	Adjusted Mean Change in Global Health Status/Quality of Life (QoL) Score From the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)	Change from baseline in global health status/quality of life (QoL) score assessed using a mixed model for repeated measures (MMRM) analysis, including all post-baseline global health status/QoL scores up to the latest scheduled visit where at least 20 patients on each treatment arm have a score. Global health status/QoL score is on a scale from 0 to 100. A higher score represents an improved health status/QoL.	EORTC QLQ-C30 assessments performed at baseline then every ~6 weeks until objective radiological disease progression. Assessed up to a maximum of 30 months.
Secondary	Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1) in Patients Confirmed as Myriad CDx gBRCAm	Time from randomisation to the earliest of objective radiological progression or death by any cause in the absence of objective progression. Objective radiological progression is defined using Response Evaluation Criteria In Solid Tumours Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Assessed in patients with a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).	Radiological scans performed at baseline then every ~6 weeks up to 24 weeks, then every ~ 12 weeks thereafter until objective radiological disease progression. Assessed up to a maximum of 30 months.
Secondary	Overall Survival (OS) at Final OS	Time from randomisation until death due to any cause.	Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 40 months.
Secondary	Overall Survival (OS) at Extended OS	Time from randomisation until death due to any cause.	Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks until Sep 2017 (final OS DCO), then every 3 months. Assessed up to a maximum of 64 months.

External Links

•   Redacted Protocol