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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04035486




Registration number
NCT04035486
Ethics application status
Date submitted
27/06/2019
Date registered
29/07/2019
Date last updated
6/08/2024

Titles & IDs
Public title
A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)
Scientific title
A Phase III, Open-label, Randomized Study of Osimertinib With or Without Platinum Plus Pemetrexed Chemo, as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA2).
Secondary ID [1] 0 0
2019-000650-61
Secondary ID [2] 0 0
D5169C00001
Universal Trial Number (UTN)
Trial acronym
FLAURA2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Osimertinib
Treatment: Drugs - Pemetrexed/Carboplatin
Treatment: Drugs - Pemetrexed/Cisplatin

Active comparator: Osimertinib 80mg QD - Osimertinib (AZD9291) 80mg QD.

All patients randomized into this will only receive Osimertinib 80mg.

Dose may be reduced to allow for the management of IP related toxicity.

Experimental: Osimertinib 80 mg QD and platinum-based chemotherapy - Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Dose may be reduced to allow for the management of IP related toxicity.


Treatment: Drugs: Osimertinib
Drug: Osimertinib (Oral)

Other Names:

AZD9291

Treatment: Drugs: Pemetrexed/Carboplatin
Drug: Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.

Treatment: Drugs: Pemetrexed/Cisplatin
Drug: Pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events Graded by Common Terminology Criteria for Adverse Event v5 (Safety Run-In Treatment Arms Only)
Timepoint [1] 0 0
From first dose date to 28 days following last dose, up to 45 months
Primary outcome [2] 0 0
Progression-free Survival (PFS) (Randomized Component)
Timepoint [2] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.3 months)
Primary outcome [3] 0 0
Sensitivity Analysis for Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment (Randomized Component)
Timepoint [3] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.2 months).
Secondary outcome [1] 0 0
Overall Survival (OS) (Safety Run-In Treatment Arms Only)
Timepoint [1] 0 0
Up to 45 months (maximum follow up 44.6 months)
Secondary outcome [2] 0 0
Duration of Response (DoR) (Safety Run-In Treatment Arms Only)
Timepoint [2] 0 0
Up to 45 months
Secondary outcome [3] 0 0
Objective Response Rate (ORR) (Safety Run-In Treatment Arms Only)
Timepoint [3] 0 0
Up to 45 months
Secondary outcome [4] 0 0
Depth of Response (Percent Change From Baseline in Tumor Diameter) (Safety Run-In Treatment Arms Only)
Timepoint [4] 0 0
Up to 45 months
Secondary outcome [5] 0 0
Disease Control Rate (DCR) by Investigator (Safety Run-In Treatment Arms Only)
Timepoint [5] 0 0
Up to 45 months
Secondary outcome [6] 0 0
Overall Survival (OS) (Randomized Component)
Timepoint [6] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 34.1 months)
Secondary outcome [7] 0 0
Landmark Overall Survival (LOS) at 1, 2, and 3 Years (Randomized Component)
Timepoint [7] 0 0
Up to approximately 33 months after the first patient is randomized (maximum follow up of 34.1 months)
Secondary outcome [8] 0 0
Objective Response Rate (ORR) (Randomized Component)
Timepoint [8] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [9] 0 0
Duration of Response (DoR) (Randomized Component)
Timepoint [9] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [10] 0 0
Depth of Response (Percent Change From Baseline in Tumor Diameter) (Randomized Component)
Timepoint [10] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [11] 0 0
Disease Control Rate (DCR) by Investigator (Randomized Component)
Timepoint [11] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [12] 0 0
Progression Free Survival 2 (PFS2) (Randomized Component)
Timepoint [12] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [13] 0 0
Time to First Subsequent Therapy (TFST) or Death (Randomized Component)
Timepoint [13] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [14] 0 0
Time to Second Subsequent Therapy (TSST) or Death (Randomized Component)
Timepoint [14] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [15] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) (Randomized Component)
Timepoint [15] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [16] 0 0
Median Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) (Randomized Component)
Timepoint [16] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [17] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 Items (EORTC QLQ-LC13) (Randomized Component)
Timepoint [17] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [18] 0 0
Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 Items (EORTC QLQ-LC13) (Randomized Component)
Timepoint [18] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [19] 0 0
Concordance of Epidermal Growth Factor Receptor (EGFR) Mutation Status Between the Local EGFR Mutation Test and the Central Cobas® EGFR Mutation Test v2 Results: Exon 19 Deletion (Randomized Component)
Timepoint [19] 0 0
Screening/Baseline
Secondary outcome [20] 0 0
Concordance of Epidermal Growth Factor Receptor (EGFR) Mutation Status Between the Local EGFR Mutation Test and the Central Cobas® EGFR Mutation Test v2 Results: L858R (Randomized Component)
Timepoint [20] 0 0
Screening/Baseline
Secondary outcome [21] 0 0
Progression-free Survival (PFS) by Investigator by Plasma Epidermal Growth Factor Receptor Mutation Status: Exon 19 Deletion - Participants With an Event (Randomized Component)
Timepoint [21] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [22] 0 0
Progression-free Survival (PFS) by Investigator by Plasma Epidermal Growth Factor Receptor Mutation Status: L858R - Participants With an Event (Randomized Component)
Timepoint [22] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [23] 0 0
Plasma Concentration of Osimertinib When Given With or Without Chemotherapy (Randomized Component)
Timepoint [23] 0 0
Pre-dose and 1-hour post-dose on Day 22; pre-dose, 1-, 2-, 4-, and 6-hours post-dose on Day 43; pre-dose and 1-hour post-dose on Day 106.
Secondary outcome [24] 0 0
Plasma Concentration of Metabolite AZ5104 When Osimertinib is Given With or Without Chemotherapy (Randomized Component)
Timepoint [24] 0 0
Pre-dose and 1-hour post-dose on Day 22; pre-dose, 1-, 2-, 4-, and 6-hours post-dose on Day 43; pre-dose and 1-hour post-dose on Day 106.
Secondary outcome [25] 0 0
Mean Cmin,ss and Mean Cmax,ss of Osimertinib (Randomized Component)
Timepoint [25] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [26] 0 0
Mean Cmin,ss and Mean Cmax,ss of AZ5104 (Randomized Component)
Timepoint [26] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [27] 0 0
Mean AUCss of Osimertinib (Randomized Component)
Timepoint [27] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [28] 0 0
Mean AUCss of AZ5104 (Randomized Component)
Timepoint [28] 0 0
Up to approximately 33 months after the first patient is randomized.
Secondary outcome [29] 0 0
Mean CLss/F of Osimertinib (Randomized Component)
Timepoint [29] 0 0
Up to approximately 33 months after the first patient is randomized.

Eligibility
Key inclusion criteria
1. Male or female, at least 18 years of age; patients from Japan at least 20 years of age.
2. Pathologically confirmed non-squamous Non-Small Cell Lung Cancer (NSCLC). NSCLC of mixed histology is allowed.
3. Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic Non-Small Cell Lung Cancer (NSCLC) (clinical stage IVA or IVB) or recurrent Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
4. The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M.
5. Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
6. WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.
7. Life expectancy >12 weeks at Day 1.
8. Willing to use contraception as appropriate during the study and for a period of time after discontinuing study treatment.
Minimum age
18 Years
Maximum age
110 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Spinal cord compression; and unstable brain metastases, with stable brain metastases who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids can be enrolled. Patients with asymptomatic brain metastases can be eligible for inclusion if in the opinion of the Investigator immediate definitive treatment is not indicated
2. Past medical history of Interstitial Lung Disease (ILD), drug-induced Interstitial Lung Disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active Interstitial Lung Disease.
3. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including Hep. B, Hep. C and HIV. Screening for chronic conditions is not required. Active infection will include any patients receiving treatment for infection.
4. QT prolongation or any clinically important abnormalities in rhythm.
5. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

* Absolute neutrophil count below the lower limit of normal (<LLN)
* Platelet count below the LLN
* Hemoglobin <90 g/L. The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted.
* ALT >2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
* AST >2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
* Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
* Creatinine clearance <60 mL/min calculated by Cockcroft and Gault equation or 24 hour urine collection (refer to Appendix I for appropriate calculation)
6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib.
7. Prior treatment with any systemic anti-cancer therapy for advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiation including chemotherapy, biologic therapy, immunotherapy, or any investigational drug. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapies, investigational agents are permitted as long as treatment was completed at least 12 months prior to the development of recurrent disease.
8. Prior treatment with an Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).
9. Major surgery within 4 weeks of the first dose of investigational product (IP). Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery are permitted.
10. Radiotherapy treatment to more than 30% of the bone marrow or( with a wide field of radiation within 4 weeks of the first dose of investigational product (IP).
11. History of hypersensitivity to active or inactive excipients of investigational product (IP) or drugs with a similar chemical structure or class to investigational product (IP).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/06/2026
Actual
Sample size
Target
Accrual to date
Final
587
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Chermside
Recruitment hospital [3] 0 0
Research Site - Elizabeth Vale
Recruitment hospital [4] 0 0
Research Site - Heidelberg
Recruitment hospital [5] 0 0
Research Site - Kogarah
Recruitment hospital [6] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kansas
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Caba
Country [15] 0 0
Argentina
State/province [15] 0 0
Ciudad de Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Cordoba
Country [17] 0 0
Argentina
State/province [17] 0 0
Santa Fe
Country [18] 0 0
Brazil
State/province [18] 0 0
Barretos
Country [19] 0 0
Brazil
State/province [19] 0 0
Florianópolis
Country [20] 0 0
Brazil
State/province [20] 0 0
Londrina
Country [21] 0 0
Brazil
State/province [21] 0 0
Porto Alegre
Country [22] 0 0
Brazil
State/province [22] 0 0
Ribeirão Preto
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Brazil
State/province [24] 0 0
São José do Rio Preto
Country [25] 0 0
Brazil
State/province [25] 0 0
São Paulo
Country [26] 0 0
Brazil
State/province [26] 0 0
Vitoria
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Chile
State/province [29] 0 0
Santiago
Country [30] 0 0
Chile
State/province [30] 0 0
Temuco
Country [31] 0 0
Chile
State/province [31] 0 0
Viña del Mar
Country [32] 0 0
China
State/province [32] 0 0
Beijing
Country [33] 0 0
China
State/province [33] 0 0
Changchun
Country [34] 0 0
China
State/province [34] 0 0
Changsha
Country [35] 0 0
China
State/province [35] 0 0
Chengdu
Country [36] 0 0
China
State/province [36] 0 0
Chongqing
Country [37] 0 0
China
State/province [37] 0 0
Guangzhou
Country [38] 0 0
China
State/province [38] 0 0
Haikou
Country [39] 0 0
China
State/province [39] 0 0
Hangzhou
Country [40] 0 0
China
State/province [40] 0 0
Harbin
Country [41] 0 0
China
State/province [41] 0 0
Hefei
Country [42] 0 0
China
State/province [42] 0 0
Jinan
Country [43] 0 0
China
State/province [43] 0 0
Nanjing
Country [44] 0 0
China
State/province [44] 0 0
Shanghai
Country [45] 0 0
China
State/province [45] 0 0
Shenyang
Country [46] 0 0
China
State/province [46] 0 0
Urumqi
Country [47] 0 0
China
State/province [47] 0 0
Wuhan
Country [48] 0 0
China
State/province [48] 0 0
Xi'an
Country [49] 0 0
China
State/province [49] 0 0
Zhengzhou
Country [50] 0 0
Czechia
State/province [50] 0 0
Olomouc
Country [51] 0 0
Czechia
State/province [51] 0 0
Ostrava - Vitkovice
Country [52] 0 0
Czechia
State/province [52] 0 0
Praha 5
Country [53] 0 0
Czechia
State/province [53] 0 0
Praha
Country [54] 0 0
France
State/province [54] 0 0
Bordeaux Cedex
Country [55] 0 0
France
State/province [55] 0 0
Lyon
Country [56] 0 0
France
State/province [56] 0 0
Montpellier
Country [57] 0 0
France
State/province [57] 0 0
Villejuif Cedex
Country [58] 0 0
India
State/province [58] 0 0
Belagavi
Country [59] 0 0
India
State/province [59] 0 0
Bengaluru
Country [60] 0 0
India
State/province [60] 0 0
Gurgaon
Country [61] 0 0
India
State/province [61] 0 0
Kolkata
Country [62] 0 0
India
State/province [62] 0 0
New Delhi
Country [63] 0 0
India
State/province [63] 0 0
Pune
Country [64] 0 0
Japan
State/province [64] 0 0
Bunkyo-ku
Country [65] 0 0
Japan
State/province [65] 0 0
Fukuoka
Country [66] 0 0
Japan
State/province [66] 0 0
Hidaka-shi
Country [67] 0 0
Japan
State/province [67] 0 0
Himeji-shi
Country [68] 0 0
Japan
State/province [68] 0 0
Iwakuni-shi
Country [69] 0 0
Japan
State/province [69] 0 0
Kanazawa
Country [70] 0 0
Japan
State/province [70] 0 0
Kashiwa
Country [71] 0 0
Japan
State/province [71] 0 0
Koto-ku
Country [72] 0 0
Japan
State/province [72] 0 0
Osaka-shi
Country [73] 0 0
Japan
State/province [73] 0 0
Sakai-shi
Country [74] 0 0
Japan
State/province [74] 0 0
Sapporo-shi
Country [75] 0 0
Japan
State/province [75] 0 0
Sendai-shi
Country [76] 0 0
Japan
State/province [76] 0 0
Sunto-gun
Country [77] 0 0
Japan
State/province [77] 0 0
Yokohama-shi
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Cheongju-si
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Goyang-si
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Seoul
Country [81] 0 0
Peru
State/province [81] 0 0
Arequipa
Country [82] 0 0
Peru
State/province [82] 0 0
Lima
Country [83] 0 0
Peru
State/province [83] 0 0
San Isidro
Country [84] 0 0
Philippines
State/province [84] 0 0
Cebu City
Country [85] 0 0
Philippines
State/province [85] 0 0
Davao City
Country [86] 0 0
Philippines
State/province [86] 0 0
Iloilo City
Country [87] 0 0
Philippines
State/province [87] 0 0
Las Pinas
Country [88] 0 0
Philippines
State/province [88] 0 0
Legazpi City
Country [89] 0 0
Philippines
State/province [89] 0 0
Quezon City
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Moscow
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Murmansk
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Saint Petersburg
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Saint-Petersburg
Country [94] 0 0
Russian Federation
State/province [94] 0 0
Syktyvkar
Country [95] 0 0
Slovakia
State/province [95] 0 0
Bratislava
Country [96] 0 0
Slovakia
State/province [96] 0 0
Kosice
Country [97] 0 0
Slovakia
State/province [97] 0 0
Poprad
Country [98] 0 0
South Africa
State/province [98] 0 0
Johannesburg
Country [99] 0 0
South Africa
State/province [99] 0 0
Port Elizabeth
Country [100] 0 0
South Africa
State/province [100] 0 0
Rondebosch
Country [101] 0 0
Taiwan
State/province [101] 0 0
Changhua
Country [102] 0 0
Taiwan
State/province [102] 0 0
Hualien City
Country [103] 0 0
Taiwan
State/province [103] 0 0
Kaohsiung City
Country [104] 0 0
Taiwan
State/province [104] 0 0
Taichung
Country [105] 0 0
Taiwan
State/province [105] 0 0
Taipei
Country [106] 0 0
Thailand
State/province [106] 0 0
Bangkok
Country [107] 0 0
Thailand
State/province [107] 0 0
Hat Yai
Country [108] 0 0
Thailand
State/province [108] 0 0
Khon Kaen
Country [109] 0 0
Thailand
State/province [109] 0 0
Muang
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Cambridge
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Leicester
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Liverpool
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Maidstone
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Manchester
Country [115] 0 0
Vietnam
State/province [115] 0 0
Hanoi
Country [116] 0 0
Vietnam
State/province [116] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The reason for the study is to find out if an experimental combination of an oral medication called osimertinib (TAGRISSO®) when used in combination with chemotherapy is more effective than giving osimertinib alone for the treatment of locally advanced or metastatic non-small cell lung cancer. Some lung cancers are due to mutations in the Deoxyribonucleic acid (DNA) which, if known, can help physicians decide the best treatment for their patients. One type of mutation can occur in the gene that produces a protein on the surface of cells called the Epidermal Growth Factor Receptor (EGFR).

Osimertinib is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets Epidermal Growth Factor Receptor (EGFR) mutations. Unfortunately, despite the benefit observed for patients treated with osimertinib, the vast majority of cancers are expected to develop resistance to the drug over time. The exact reasons why resistance develops are not fully understood but based upon clinical research it is hoped that combining osimertinib with another type of anti-cancer therapy known as chemotherapy will delay the onset of resistance and the worsening of a patient's cancer.

In total the study aims to enroll approximately 586 patients, consisting of approximately 30 patients who will participate in a safety run-in component of the trial, and approximately 556 who will receive osimertinib alone or osimertinib in combination with chemotherapy in the main trial. In the main part of the trial there is a one in two chance of receiving osimertinib alone, and the treatment is decided at random by a computer.

The study involves a Screening Period, Treatment Period, and Follow up Period. Whilst receiving study medication, it is expected patients will attend, on average, approximately 15 visits over the first 12 months and then approximately 4 visits per year afterwards. Each visit will last about 2 to 6 hours depending on the arrangement of medical assessments by the study centre.
Trial website
https://clinicaltrials.gov/study/NCT04035486
Trial related presentations / publications
Planchard D, Feng PH, Karaseva N, Kim SW, Kim TM, Lee CK, Poltoratskiy A, Yanagitani N, Marshall R, Huang X, Howarth P, Janne PA, Kobayashi K. Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study. ESMO Open. 2021 Oct;6(5):100271. doi: 10.1016/j.esmoop.2021.100271. Epub 2021 Sep 17.
White MN, Piotrowska Z, Stirling K, Liu SV, Banwait MK, Cunanan K, Sequist LV, Wakelee HA, Hausrath D, Neal JW. Combining Osimertinib With Chemotherapy in EGFR-Mutant NSCLC at Progression. Clin Lung Cancer. 2021 May;22(3):201-209. doi: 10.1016/j.cllc.2021.01.010. Epub 2021 Jan 27.
Asahina H, Tanaka K, Morita S, Maemondo M, Seike M, Okamoto I, Oizumi S, Kagamu H, Takahashi K, Kikuchi T, Isobe T, Sugio K, Kobayashi K. A Phase II Study of Osimertinib Combined With Platinum Plus Pemetrexed in Patients With EGFR-Mutated Advanced Non-Small-cell Lung Cancer: The OPAL Study (NEJ032C/LOGIK1801). Clin Lung Cancer. 2021 Mar;22(2):147-151. doi: 10.1016/j.cllc.2020.09.023. Epub 2020 Oct 16.
Public notes

Contacts
Principal investigator
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Pasi A. Jänne, MD
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Dana Farber Cancer Institute, 450 Brookline Avenue, LC4114, Boston, MA 02215, USA
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Contact person for public queries
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04035486