Clinical trial NCT02151981: AZD9291 (Osimertinib) Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Phase III, Open Label, Randomized Study of AZD9291 Versus Platinum-Based Doublet Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene (AURA3).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anticancer Treatment
Keywords: Advanced Non-Small Cell Lung Cancer; T790M Mutation Positive
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-06-02
Enrollment: 421
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene

Detailed description: This is a phase III, open label, randomized study assessing Osimertinib (80 mg, orally, once daily) versus platinum-based doublet chemotherapy (standard of care) in subjects with confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive NSCLC, who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a T790M mutation within the EGFR Gene. Subjects must be chemotherapy naive and must agree to provide a biopsy for central confirmation of T790 mutation status following confirmed disease progression on their first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or afatinib). Suitable subjects will then be randomized to receive either Osimertinib (80mg orally, once daily) or platinum-based doublet chemotherapy (pemetrexed 500 mg/m2 + carboplatin area under the plasma concentration-time curve AUC 5 or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2) on Day 1 of every 21-day cycle in a 2:1 (Osimertinib: platinum-based doublet chemotherapy) ratio. Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review, they will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These subjects may continue treatment with Osimertinib even after disease progression, as long as they are continuing to show clinical benefit, as judged by the investigator. The primary objective of the study is to assess the efficacy of Osimertinib compared with platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS), using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1), as well as asensitivity analysis of Progression Free Survival using Blinded Independent Central Review (BICR).

Eligibility criteria: Inclusion Criteria:

* Subjects with histologically or cytologically documented NSCLC.
* Locally advanced or metastatic NSCLC
* Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment
* Eligible to receive treatment with the selected doublet-chemotherapy
* Central confirmation of T790M+ mutation status
* World Health Organization (WHO) performance status 0-1
* At least one lesion, not previously irradiated.

Exclusion Criteria:

* • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of starting 1st EGFR TKI treatment
* Treatment with more than one prior line of treatment for advanced NSCLC
* Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8 days or approximately 5x half-life of the first dose of study treatment
* Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment
* Previous treatment with Osimertinib, or a 3rd generation EGFR TKI

For subjects who cross-over to Osimertinib:

* Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by independent central imaging review.
* At least 14 days since last dose of platinum-based doublet chemotherapy

Primary outcomes:
measure: Progression Free Survival (PFS) by Investigator Assessment
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
Secondary outcomes:
measure: Objective Response Rate (ORR) by Investigator Assessment
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
measure: Duration of Response (DoR) by Investigator Assessment
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
measure: Disease Control Rate (DCR) by Investigator Assessment
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
measure: Tumour Shrinkage by Investigator Assessment
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression up to 19 months (at the time of the primary PFS analysis).
measure: Secondary: Overall Survival (OS)
timeFrame: From date of randomization until time of final OS analysis, a median follow-up of 43 months
Other outcomes:
measure: Time to First Subsequent Therapy (TFST)
timeFrame: From date of randomisation until time of final OS analysis, a median follow-up of 43 months
measure: Time to Second Subsequent Therapy (TSST)
timeFrame: From date of randomisation until time of final OS analysis, a median follow-up of 43 months
Locations:
city: Anaheim
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Norwalk
country: United States
facility: Research Site
state: Connecticut
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Park Ridge
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Marrero
country: United States
facility: Research Site
state: Louisiana
city: Chevy Chase
country: United States
facility: Research Site
state: Maryland
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Brick
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: Lacey
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
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state: Washington
city: Milwaukee
country: United States
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state: Wisconsin
city: Darlinghurst
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Kogarah
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Woolloongabba
country: Australia
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Ürümqi
country: China
facility: Research Site
city: Clermont Ferrand
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Marseille Cedex 20
country: France
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city: Paris
country: France
facility: Research Site
city: Strasbourg Cedex
country: France
facility: Research Site
city: Toulouse Cedex 09
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Gerlingen
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Avellino
country: Italy
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Akashi-shi
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fukuoka
country: Japan
facility: Research Site
city: Hirakata-shi
country: Japan
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city: Kanazawa
country: Japan
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city: Kitaadachi-gun
country: Japan
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city: Kobe-shi
country: Japan
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city: Kurashiki-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Natori-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Ulsan
country: Korea, Republic of
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Oaxaca
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Ekaterinburg
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: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Changhua
country: Taiwan
facility: Research Site
city: Hsinchu
country: Taiwan
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
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: Aberdeen
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Huddersfield
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Guangdong General Hospital, Guangdong, 510030, China
name: Yilong Wu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas/M.D. Anderson Cancer Center, Houston, Tx, USA
name: Vassiliki A Papadimitrakopoulou, MD
role: PRINCIPAL_INVESTIGATOR
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