LUX-Lung 7: A Phase IIb Trial of Afatinib(BIBW2992) Versus Gefitinib for the Treatment of 1st Line EGFR Mutation Positive Adenocarcinoma of the Lung

Lung Neoplasms Clinical Trial

Official title:

LUX-Lung 7: A Randomised, Open-label Phase IIb Trial of Afatinib Versus Gefitinib as First-line Treatment of Patients With EGFR Mutation Positive Advanced Adenocarcinoma of the Lung

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01466660
• Other study ID #: 1200.123
• Secondary ID: 2011-001814-33
• Status: Completed
• Phase: Phase 2
• Start date: December 13, 2011
• Est. completion date: April 12, 2019

Study information

• Verified date: March 2020
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomised, open-label, phase IIb trial of afatinib to compare to gefitinib in first-line treatment setting with patients who are having epidermal growth factor receptor mutation positive advanced adenocarcinoma of the lung.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 319
• Est. completion date: April 12, 2019
• Est. primary completion date: April 8, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion criteria:

1. Pathologically confirmed diagnosis of Stage IIIB / IV adenocarcinoma of the lung.

2. Documented activating epidermal growth factor receptor mutation (Del19 and/or L858R) with tumour tissues.

3. At least one measurable lesion according to response evaluation criteria in solid tumours version 1.1

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

5. Age >= 18 years.

6. Adequate organ function as defined by the following criteria:

Serum aspartate transaminase(AST) and serum alanine transaminase(ALT) =< 3 x upper limit of normal (ULN), or AST and ALT =<5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin =<1.5 x ULN Absolute neutrophil count (ANC) >=1.5 x 109/L Creatinine clearance > 45ml / min Platelets >= 75 x 109/L

Exclusion criteria:

1. Prior systemic chemotherapy for stage IIIB or IV non-small cell lung cancer. Neo-/adjuvant chemotherapy, chemoradiation or radiotherapy is permitted if at least 12 months has elapsed prior to disease progression.

2. Prior treatment with epidermal growth factor receptor targeting small molecules or antibodies.

3. Major surgery within 4 weeks of study randomisation.

4. Active brain metastases

5. Meningeal carcinomatosis.

6. Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured in the opinion of investigator.

7. Known pre-existing interstitial lung disease.

8. Clinically relevant cardiovascular abnormalities as judged by the investigator.

9. Cardiac left ventricular function with resting ejection fraction of less than institutional lower limit of normal.

10. Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 months after treatment has ended.

11. Pregnancy or breast-feeding.

12. Active hepatitis and/or known HIV carrier

13. Any prohibited concomitant medications for therapy with afatinib or gefitinib

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Lung Neoplasms

Intervention

Drug:
• Afatinib
afatinib once daily
• gefitinib
Gefitinib once daily

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Chris Obrien Lifehouse	Camperdown	New South Wales
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Austin Health	Heidelberg	Victoria
Australia	St George Hospital	Kogarah	New South Wales
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Haematology & Oncology Clinics of Australasia (HOCA)	South Brisbane	Queensland
Canada	Cross Cancer Institute (University of Alberta)	Edmonton	Alberta
Canada	Montreal General Hospital - McGill University Health Centre	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	British Columbia Cancer Agency (BCCA) - Fraser Valley Cancer	Surrey	British Columbia
Canada	BC Cancer Agency - Vancouver	Vancouver	British Columbia
China	Beijing Cancer Hospital	Beijing
China	Cancer Hospital of Chinese Academy of Medical Science	Beijing
China	Sun Yat-Sen University Cancer Center	Guangzhou
China	The Affiliated Cancer Hospital, Guangxi Medical University	Nan Ning
China	Shanghai Chest Hospital	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	The First Hospital of Chinese Medical University	Shenyang
France	CTR Oncologie du Pays Basque, Onco, Bayonne	Bayonne
France	CTR François Baclesse	Caen
France	HOP Intercommunal	Créteil
France	HOP Michallon	La Tronche
France	HOP Dupuytren 1	Limoges Cedex
France	CTR Leon Berard	Lyon
France	CTR René Gauducheau	Saint Herblain
France	HOP Sud-Réunion, Pneumo, Saint Pierre	St-Pierre - La Réunion
Germany	Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH	Essen
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Hong Kong	Queen Mary Hospital	Hongkong
Hong Kong	Prince of Wales Hospital	Shatin
Ireland	St James's Hospital	Dublin
Ireland	Beaumont Hospital	Dublin 9
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Norway	Oslo Universitetssykehus HF, Radiumhospitalet	Oslo
Singapore	Johns Hopkins Singapore International Medical Center	Singapore
Singapore	National Cancer Centre	Singapore
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Regional Universitario de Málaga	Malaga
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Virgen del Rocío	Sevilla
Sweden	Sahlgrenska US, Göteborg	Göteborg
Sweden	Universitetssjukhuset, Linköping	Linköping
Sweden	Skånes universitetssjukhus, Lund	Lund
Sweden	Karolinska Univ. sjukhuset	Stockholm
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	NCKUH	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipe Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital(Linkou)	Tao-Yuan
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Birmingham City Hospital	Birmingham
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Surrey County Hospital	Guildford

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Australia,  Canada,  China,  France,  Germany,  Hong Kong,  Ireland,  Korea, Republic of,  Norway,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Progression-free survival (PFS) defined as the time from date of randomisation to date of disease progression, or date of death if a patient died earlier. Participants with no event (Disease progression (PD) or death) were censored. PD was primarily evaluated for the primary analysis by an independent central imaging review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started, together with an absolute increase in the SoD of target lesions of at least 5 millimetre (mm) or the appearance of one or more new lesions. For the final analysis (analysis cut-off date 12 April 2019) status and date of PD were determined by investigator assessment.	From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
Primary	Time to Treatment Failure (TTF) (Main Overall Survival Analysis Cut-off Date, 08 April 2016)	Time to Treatment Failure (TTF) which was the time from the date of randomisation to the date of i.e. permanent treatment discontinuation for any reason.	From first drug administration until last drug administration, up to 1482 days
Primary	Overall Survival	Overall survival (OS) which was defined as the time from the date of randomisation to the date of death. Participants for whom there is no evidence of death at the time of the analysis will be censored at the date that they were last known to be alive.	From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on death, up to 2465 days.
Secondary	Objective Response Rate	Objective response rate (ORR) which was defined as the number of participants with best overall response of complete response (CR) or partial response (PR) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. divided by the total number of participants who received treatment. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions from baseline. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.	From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
Secondary	Time to Objective Response	Number of participants with objective response (best overall response of complete response or partial response) to study treatment over time, cumulative number of participants is displayed. Time to objective response was defined as the time from randomisation to the first recorded objective response. For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.	From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
Secondary	Duration of Objective Response	Duration of objective response defined as the time of first objective response (best overall response of complete response or partial response) to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) objective response was determined by investigator assessment.	From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
Secondary	Disease Control	Percentage of participants with disease control which was defined as the number of participants with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. divided by the total number of participants who received treatment. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Responses of SD were only considered if they occur =42 days from date of randomisation. For the final analysis (analysis cut-off date 12 April 2019) disease control was determined by investigator assessment.	From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
Secondary	Duration of Disease Control	Duration of disease control defined as the time from randomisation to the time of progression or death, whichever occurred first (or date of censoring for progression free survival). For the final analysis (analysis cut-off date 12 April 2019) the status and date of disease progression were determined by investigator assessment.	From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
Secondary	Tumour Shrinkage (Main Overall Survival Analysis Cut-off Date, 08 April 2016)	Tumour shrinkage assessed by minimum sum of post-baseline target lesion diameters recorded after randomisation. A positive value shows a decrease in tumour size.	From first drug administration until last drug administration, up to 1482 days
Secondary	Health-related Quality of Life (Primary Analysis Cut-off Date, 21 August 2015)	Health-related quality of life (HRQoL) measured using European Quality of life - 5 Dimensions (EQ-5D) score for United Kingdom (UK) and Belgium and European European Quality Visual Analogue Scale (EQ-VAS).; EQ-5D utility scores range from 0 (worst health) to 1 (full health).; EQ-VAS scores range from 0 (worst imaginable health state) to 100 (best imaginable health state).; Results display the mean score up to 56 weeks.	Every 8 weeks, up to 56 weeks

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