FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2020/06/025980 [Registered on: 18/06/2020] Trial Registered Prospectively
Last Modified On: 01/09/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   A clinical trial to check if combination therapy of osimertinib plus platinum plus pemetrexed is better than monotherapy (osimertinib) for patient with Epidermal growth factor receptor positive Locally Advance or Metastatic Non- small Cell Lung Cancer.  
Scientific Title of Study   A Phase III, Open-label, Randomized Study of Osimertinib with or without Platinum Plus Pemetrexed Chemotherapy, as First-line Treatment in Patients with Epidermal Growth Factor Receptor (EGFR) Mutation- Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA2)  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
 
Name  Mr Tapankumar M Shah 
Designation  Country Director, Clinical Operations 
Affiliation  AstraZeneca Pharma India Ltd 
Address  AstraZeneca Pharma India Ltd. Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road Bangalore

Bangalore
KARNATAKA
560064
India 
Phone  91-9535104975  
Fax  91-8067748857   
Email  tapankumar.shah@astrazeneca.com  
 
Details of Contact Person
Public Query
 
Name  Mr Tapankumar M Shah 
Designation  Country Director, Clinical Operations 
Affiliation  AstraZeneca Pharma India Ltd 
Address  AstraZeneca Pharma India Ltd. Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road Bangalore

Bangalore
KARNATAKA
560064
India 
Phone  91-9535104975  
Fax  91-8067748857   
Email  tapankumar.shah@astrazeneca.com  
 
Source of Monetary or Material Support  
AstraZeneca AB (Study Sponsor company) 151 85 Sodertalje, Sweden  
 
Primary Sponsor  
Name  AstraZeneca AB  
Address  151 85 Sodertalje, Sweden 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Argentina
Australia
Brazil
Canada
Chile
China
Czech Republic
Democratic People's Republic of Korea
France
India
Japan
Peru
Philippines
Russian Federation
Slovakia
South Africa
Taiwan
Thailand
United Kingdom
United States of America
Viet Nam  
Sites of Study  
No of Sites = 17  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Hari Goyal  Artemis Hospital  Dept. Of Medical Oncology Sector-51, Gurugram PIN - 122001
Gurgaon
HARYANA 
0124-4511111
0124-4588899
harig@artemishospitals.com 
Dr Arun Rajagopal Warrier  Aster Medcity  Dept. Of Medical Oncology Kuttisahib Road, South Chittoor, Cheranalloor, Kochi PIN 682027
Ernakulam
KERALA 
04846699999

drarun.warrierr@asterhospital.com 
Dr Nirmal Vivek Raut  Bhaktivedanta Hospital & Research Institute  Srishti Complex, Bhaktivedanta Swami Marg, Mira Road (East) PIN - 401107
Thane
MAHARASHTRA 
029452500
02228459885
drnirmalraut@gmail.com 
Dr Chetan Dilip Deshmukh  Deenanath Mangeshkar Hospital & Research Center  Dept. Of Medical Oncology Near Mhatre Bridge, Erandwane, PIN 411004
Pune
MAHARASHTRA 
02066023000

drchetandeshmukh@redffmail.com 
Dr Ashish Kaushal  HCG Cancer Centre, Ahmedabad  Dept. Of Medical Oncology Sola-Science City Road, Near Sola Bridge, S.G. Highway, Ahmedabad - 380060
Ahmadabad
GUJARAT 
07940410101
07940410227
drashish4@yahoo.co.in 
Dr Shruti Kate  HCG Manavata Cancer Centre  Dept. Of Medical Oncology Behind Shivang Auto, Mumbai Naka, Nasik - 422002
Nashik
MAHARASHTRA 
02536661111

drshruti@mcrinasik.com 
Dr Rohan Bhise  KLES Dr. Prabhakar Kore Hospital &Medical Research Centre  Nehrunagar Belagavi PIN 590010
Belgaum
KARNATAKA 
08312470400
09448866712
rohanbhise30@gmail.com 
Dr Praveena Voonna  Mahatma Gandhi Cancer Hospital and Research Institute  Dept. Of Medical Oncology 1 7 MVP Colony, Vishakhapatnam PIN 530017
Visakhapatnam
ANDHRA PRADESH 
08912878787
08912506103
praveena.voonna@gmail.com 
Dr Amit Rauthan  Manipal Hospital  Dept. Of Medical Oncology 98, HAL Airport Road, PIN-560017
Bangalore
KARNATAKA 
08040119000

amit.rauthan@manipalhospitals.com 
Dr Gore Adawaita Anant  Prince Aly Khan Hospital  Dept. Of Medical Oncology Prince Aly Khan Hospital Aga Hall, Nesbit Road, Mazagaon, MumbaI PIN 400010
Mumbai
MAHARASHTRA 
02223777800
02223743820
adygore@gmail.com 
Dr Sumit Goyal  Rajiv Gandhi Cancer Institute and Research Centre  Dept. Of Medical Oncology Sector-5, Rohini PIN 110085
New Delhi
DELHI 
01147022222

drsumitgoyal@gmail.com 
Dr Shailesh Arjun Bondarde  Shatabdi Hospital  Dept. Of Medical Oncology Mumbai Naka, Suyojit City Centre, Opp. Mahamarg Bus Stand, PIN 422001
Nashik
MAHARASHTRA 
02532591159

shaileshbondarde1971@gmail.com 
Dr Lokesh KN  Shettys Hospital  Dept. Of Medical Oncology Plot No: 11 & 12, 12th F Main, Kaveri Nagar Kodichikkanahalli, Bommanhalli, PIN-560068
Bangalore
KARNATAKA 
08040943039

knloki@gmail.com 
Dr Satheesh C T  Sri Venkateshwara Hospital  Dept. Of Medical Oncology #27, 29th Main Road, Rashtra Kuvempu Nagara, BTM 2nd stage, BTM layout, PIN 560076
Bangalore
KARNATAKA 
08049730808
08025630006
drsatheeshct@gmail.com 
Dr Harwani Arun Thakurdas   Sujan Surgical Cancer Hospital and Amravati Cancer Foundation  Dept. Of Medical Oncology 52/B, Shankar Nagar, Main Road, Maharashtra PIN 444606
Amravati
MAHARASHTRA 
09823170639
07212578568
drarunharwani@gmail.com 
Dr Bivas Biswas   Tata Medical Center  Dept. Of Medical Oncology 14 MAR EW, Newtown, Rajarhat, PIN 700 160
Kolkata
WEST BENGAL 
03366057000

bivas.biswas@tmckolkata.com 
Dr Nikhil S Ghadyalpatil  Yashoda Hospital  Dept. Of Medical Oncology RajBhavan Rd, Matha Nagar, Somajiduda PIN - 500082
Hyderabad
TELANGANA 
040-67232321

nikhilghadyalpatil@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 17  
Name of Committee  Approval Status 
Amravati Ethics Committee  Submittted/Under Review 
Artemis Health Sciences Institutional Ethics Committee  Approved 
Bhaktivedanta Hospital Ethics Committee  Submittted/Under Review 
Ethics Committee of Manipal Hospitals  Submittted/Under Review 
HCG Multi Specialty Ethics Committee, Ahmedabad   Approved 
Institutional Ethics Committee Deenanath Mangeshkar Hospital & Research Center  Submittted/Under Review 
Institutional Ethics Committee KAHER (Formerly known to be KLE University)  Submittted/Under Review 
Institutional Ethics Committee, Prince Aly Khan Hospital  Submittted/Under Review 
Institutional Ethics Committee, Yashoda Academy of Medical Education and Research  Submittted/Under Review 
Institutional Ethics Committeee Aster Medcity  Submittted/Under Review 
Institutional Review Board Rajiv Gandhi Cancer Institute and Research Centre  Approved 
Institutional Review Board Tata Medical Center, Kolkata  Approved 
Mahatma Gandhi cancer Hospital and Research Institute Institutional Review Committee  Approved 
Manavata Clinical Research Institute Ethics Committee  Submittted/Under Review 
Shatabdi Hospital Ethics Committee  Approved 
Shety’s Hospital Ethics Committee  Approved 
Sri Venkateshwara Hospital Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  C349||Malignant neoplasm of unspecifiedpart of bronchus or lung,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Osimertinib   Monotherapy 
Intervention  Osimertinib with Cisplatin or Carboplatin plus Pemetrexed   1:1Assignment 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
2.Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses
3. For patients who agree to the optional genetic testing, provision of signed and dated genetic testing section of the written Main ICF prior to collection of a sample for genetic analysis for inclusion in the optional genetic research as allowed by local regulations

Age

4.Male or female, at least 18 years of age; patients from Japan at least 20 years of age

Type of patient and disease characteristics
5.Pathologically confirmed nonsquamous NSCLC
6.Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC (per Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology), not amenable to curative surgery or radiotherapy
7. The tumor harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing
8.Mandatory provision of a baseline plasma sample and an unstained, archival tumor tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status
9. Patients must have untreated advanced NSCLC not amenable to curative surgery or radiotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior to the development of recurrent disease
10.WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks
11.Life expectancy >12 weeks at Day 1
12.At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis of ≥15 mm) with CT or MRI, and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumor assessment scans

Reproduction
13.Female patients who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner must be using highly effective contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of IP or must have evidence of non-child-bearing potential by fulfilling 1 of the following criteria at screening:
i. Post-menopausal, defined as more than 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
ii. Women under 50 years old would be considered as postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution
iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
14.Male patients must be willing to use barrier contraception
 
 
ExclusionCriteria 
Details  Medical conditions

1.Spinal cord compression; symptomatic and unstable brain metastases, except for those patients 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. 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 ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
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 hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
4.Any of the following cardiac criteria
i. Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived QTcF value
ii. Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG; eg, complete left bundle branch block, third-degree heart block, seconddegree heart block
iii. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including serum/plasma potassium, magnesium and calcium below the LLN, heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes
correction of electrolyte abnormalities to within normal ranges can be performed during screening
5.Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
i. Absolute neutrophil count below the lower limit of normal ( ii. Platelet count below the LLN
iii. Hemoglobin <90 g/L
The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted
iv. 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
v. AST >2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases
vi. Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of documented Gilberts Syndrome (unconjugated hyperbilirubinemia) or liver
vii. metastases
viii. Creatinine clearance <60 mL/min calculated by Cockcroft and Gault equation
6.Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of IP.
7.Any unresolved toxicities from prior systemic therapy (eg, adjuvant chemotherapy) greater than CTCAE Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy.
8.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

Prior/concurrent therapy
9.Prior treatment with any systemic anti-cancer therapy for advanced 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.
10.Prior treatment with an EGFR-TKI.
11.Major surgery within 4 weeks of the first dose of IP. Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery (VATS) are permitted.
12.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 IP.
13.Current use of (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3 weeks prior)

Prior/concurrent clinical study experience
14.Participation in another clinical study with an investigational product during the 4 weeks prior to Day 1. Patients in the follow-up period of an interventional study are permitted

Other exclusion

15.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and staff at the study site).
16.Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
17.Previous treatment allocation (safety run in) or randomization (randomization period) in the present study.
18.Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
19.History of hypersensitivity to active or inactive excipients of IP or drugs with a similar chemical structure or class to IP.
20.Contraindication for pemetrexed and cisplatin/carboplatin according to local approved label.
21.In addition, the following are considered criteria for exclusion from the exploratory genetic research:
i. Prior allogeneic bone marrow transplant
ii. Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection

 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To evaluate the safety and tolerability of osimertinib
plus chemotherapy  
RECIST 1.1 Evaluation- every 12 weeks from the 1st dose of IP.

IDMC meeting at following timepoints
60 patients across both treatment arm with at least 28 day of follow up.
150 patients across both treatment arm with at least 28 day of follow up.
300 patients across both treatment arm with at least 28 day of follow up.

After completion of Recruitment
Every 6 months until primary PFS analysis data cut off (278 progression events)
 
 
Secondary Outcome  
Outcome  TimePoints 
To assess the efficacy of osimertinib plus Chemotherapy  ORR, DoR; depth of response; DCR by Investigator;OS;
 
To assess the PK of osimertinib when given with Chemotherapy  state plasma concentrations and appropriate PK parameters (CLss/F, Cmax,ss Cmin,ss and AUCss) of osimertinib and its metabolite, AZ5104 will be summarized
 
Exploratory Objective To explore how changes in plasma-based biomarkers (eg, ctDNA, proteomic) correlate with response
 
Quantitative ctDNA analysis using specific EGFR biomarkers or broader cancer biomarker panel in longitudinal plasma samples, to assess ctDNA clearance and correlate with response (eg, PFS)
 
To collect and store DNA for genetic research to explore how genetic variations may affect clinical parameters, risk and prognosis of diseases, and the response to medications
 
Correlation of polymorphisms with variation in PK, pharmacodynamics, safety or response observed in patients treated with osimertinib plus chemotherapy
 
To explore efficacy biomarkers and biomarker changes in baseline, longitudinal and progression
samples (plasma and tumor tissue) for correlation with response
 
Assessment of innate and acquired resistance mechanisms and biomarkers of response including but not limited to mutations in, amplifications and expression of EGFR, TP53, HER2, MET and relevant pathway genes Proteomic and/or gene expression analysis eg, biomarkers of inflammation
 
To collect and store tumor, serum and plasma samples for potential exploratory research into factors that may influence susceptibility to development of NSCLC and/or response to osimertinib and/or chemotherapy (where response is defined broadly to include efficacy, tolerability or safety) and to assess the relationship between tissue and/or bloodborne biomarkers and selected efficacy endpoints. Tissue and plasma samples may be used to support diagnostic development.
 
Key genetic, gene expression and proteomic markers to include, but not limited to, EGFR mutations, HER, and proto-oncogene encoding cMET expression and/or amplification. Relationship between PK and blood-borne biomarkers. Diagnostic development.
 
 
Target Sample Size   Total Sample Size="556"
Sample Size from India="50" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   07/07/2020 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  02/07/2020 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="6"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Yet Recruiting 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   Not yet 
Brief Summary  

A Phase III, Open-label, Randomized Study of Osimertinib with or without Platinum Plus Pemetrexed Chemotherapy, as First-line Treatment in Patients with Epidermal Growth Factor Receptor (EGFR) Mutation- Positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA2)

Approximately 556 new patients randomized in a 1:1 ratio to receive osimertinib alone or osimertinib with pemetrexed and either cisplatin or carboplatin

Patients will be stratified by race (Chinese/Asian vs. non Chinese/Asian vs. non-Asian), WHO PS (0 vs. 1), and method for tissue testing (central vs. local)

It is anticipated that approximately 60% Asian patients and 40% non-Asian patients will be recruited.

The Investigator will decide before randomization which chemotherapy regimen (carboplatin/pemetrexed or cisplatin/pemetrexed) a patient would receive in case the patient is assigned to the osimertinib plus chemotherapy arm.

Randomized treatment will continue until RECIST 1.1-defined progression by Investigator or until another discontinuation criterion is met. Patients can continue to receive study treatment through progression if, in the judgement of the Investigator, they are receiving clinical benefit and do not meet any of the discontinuation criteria. However, if the patient is deemed to have clinically significant unacceptable or irreversible toxicities, rapid tumor progression, or symptomatic progression requiring urgent medical intervention (eg, CNS metastases, respiratory failure, spinal cord compression) study treatment must be discontinued.

 
Close