Clinical trial NCT02000622: 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.
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer Metastatic
BRCA 1 Gene Mutation
BRCA 2 Gene Mutation
Keywords: Breast Cancer
Metastatic
Olaparib
BRCA
PARP inhibitor
HER2
chemotherapy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Myriad Genetic Laboratories, Inc.
name: Merck Sharp & Dohme LLC
First posted: 2013-12-04
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival (PFS) Using Blinded Independent Central Review (BICR) According to Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)
timeFrame: 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 outcomes:
measure: Time to Second Progression or Death (PFS2)
timeFrame: 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.
measure: Overall Survival (OS)
timeFrame: Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 30 months.
measure: Objective Response Rate (ORR) Using Blinded Independent Central Review (BICR) Data Assessed by Modified Response Evaluation Criteria In Solid Tumours (RECIST v1.1)
timeFrame: 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.
measure: 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)
timeFrame: EORTC QLQ-C30 assessments performed at baseline then every ~6 weeks until objective radiological disease progression. Assessed up to a maximum of 30 months.
measure: 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
timeFrame: 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.
measure: Overall Survival (OS) at Final OS
timeFrame: Survival status reviewed every 3 weeks until treatment discontinued, then every 8 weeks. Assessed up to a maximum of 40 months.
measure: Overall Survival (OS) at Extended OS
timeFrame: 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.
Other outcomes:
measure: Time to First Subsequent Cancer Therapy or Death (TFST)
timeFrame: Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
measure: Time to Second Subsequent Cancer Therapy or Death (TSST)
timeFrame: Subsequent cancer therapy status reviewed every 8 weeks following study treatment discontinuation. Assessed up to a maximum of 30 months.
measure: Time to First Subsequent Cancer Therapy or Death (TFST) at Extended OS
timeFrame: 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.
measure: Time to Second Subsequent Cancer Therapy or Death (TSST) at Extended OS
timeFrame: 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.
Locations:
city: San Diego
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Plantation
country: United States
facility: Research Site
state: Florida
city: Columbus
country: United States
facility: Research Site
state: Georgia
city: Marietta
country: United States
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state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Niles
country: United States
facility: Research Site
state: Illinois
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Lafayette
country: United States
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state: Louisiana
city: Boston
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state: Massachusetts
city: Boston
country: United States
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state: Massachusetts
city: Boston
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state: Massachusetts
city: Detroit
country: United States
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state: Michigan
city: Grand Rapids
country: United States
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state: Michigan
city: Rochester
country: United States
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state: Minnesota
city: Saint Louis Park
country: United States
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state: Minnesota
city: Jackson
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state: Mississippi
city: Columbia
country: United States
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state: Missouri
city: Saint Louis
country: United States
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state: Missouri
city: Lebanon
country: United States
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state: New Hampshire
city: Commack
country: United States
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state: New York
city: Harrison
country: United States
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state: New York
city: New York
country: United States
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state: New York
city: New York
country: United States
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state: New York
city: Rockville Centre
country: United States
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city: Syracuse
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city: Cincinnati
country: United States
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state: Ohio
city: Cleveland
country: United States
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city: Cleveland
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city: Sayre
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city: Houston
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city: Tyler
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city: Burlington
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state: Vermont
city: Plovdiv
country: Bulgaria
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country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Varna
country: Bulgaria
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city: Vratza
country: Bulgaria
facility: Research Site
city: Beijing
country: China
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city: Beijing
country: China
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city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
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city: Changsha
country: China
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city: Chengdu
country: China
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city: Dalian
country: China
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city: Guangzhou
country: China
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city: Hangzhou
country: China
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city: Harbin
country: China
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city: Nanjing
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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city: Tianjin
country: China
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city: Brno
country: Czechia
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city: Olomouc
country: Czechia
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city: Praha 2
country: Czechia
facility: Research Site
city: Caen Cedex
country: France
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city: Montpellier
country: France
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city: Rouen
country: France
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city: Strasbourg Cedex
country: France
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city: Villejuif
country: France
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Nyíregyháza
country: Hungary
facility: Research Site
city: Veszprém
country: Hungary
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
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city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
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city: Nagoya-shi
country: Japan
facility: Research Site
city: Osaka-city
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Shinagawa-ku
country: Japan
facility: Research Site
city: Suita-city
country: Japan
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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facility: Research Site
city: Estado de México
country: Mexico
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city: Merida
country: Mexico
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country: Mexico
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country: Mexico
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country: Peru
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country: Peru
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country: Peru
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country: Peru
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country: Peru
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country: Poland
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country: Poland
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city: Grzepnica
country: Poland
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city: Tarnobrzeg
country: Poland
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city: Warszawa
country: Poland
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city: Warszawa
country: Poland
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city: Łódź
country: Poland
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city: Bucharest
country: Romania
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city: Bucuresti
country: Romania
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city: Bucuresti
country: Romania
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city: Cluj Napoca
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Ivanovo
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saransk
country: Russian Federation
facility: Research Site
city: St-Petersburg
country: Russian Federation
facility: Research Site
city: St.Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Zürich
country: Switzerland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Gaziantep
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
facility: Research Site
city: Konya
country: Turkey
facility: Research Site
city: Mersin
country: Turkey
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: Colchester
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Memorial Sloan-Kettering Cancer Center, New York
name: Mark Robson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.