BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)

NCT01121393 | Completed Phase 3 Results

• 1 other identifier: 1200.34
• Study Type: interventional
• Target: 364
• Locations: 3 countries
• Sites: 36

Brief Summary

To investigate the efficacy and safety of BIBW 2992 compared to standard first-line chemotherapy in patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation

Conditions

Carcinoma, Non-Small-Cell Lung; Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  The primary endpoint was progression-free survival (PFS) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival was defined as the time from randomisation to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not have a PFS. Only data collected up until the analysis cut-off date (27 December 2013) were considered. Median time results from unstratified Kaplan-Meier estimates.

  Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 168

Secondary Outcomes (17)

• Objective Response (OR)

  Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

• Disease Control (DC)

  Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

• Overall Survival (OS)

  From randomisation up to 374 weeks

• Time to Objective Response (OR)

  Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

• Duration of Objective Response

  Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374

Study Arms (2)

Arm A BIBW 2992

EXPERIMENTAL

Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity

Drug: BIBW 2992

Arm B Chemotherapy

ACTIVE COMPARATOR

Patients receive Gemcitabine and Cisplatin, maximum is 6 courses

Drug: Gemcitabine+Cisplatin

Interventions

Gemcitabine+Cisplatin DRUG

Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.

Arm B Chemotherapy

BIBW 2992 DRUG

starting dose is 40 mg, in the event of no or minimal drug-related adverse events after one course, the dose will be increased to 50mg. in the event of certain drug related Adverse Event (AE), dose reduction will be increments of 10 mg, with the lowest dose being 20mg.

Arm A BIBW 2992

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• pathologically confirmed diagnosis of stage IIIB or stage IV adenocarcinoma of the Lung
• EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory analysis of tumor biopsy material
• Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST)1.1
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
• Age\>=18 years
• life expectancy of at least three months
• Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines.

You may not qualify if:

• Prior chemotherapy for relapsed and/or metastatic NSCLC.
• Prior treatment with EGFR targeting small molecules or antibodies.
• Radiotherapy or surgery(other than biopsy) within 4 weeks prior to randomization
• Active brain metastases
• Any other current malignancy or malignancy diagnosed within the past 5 years
• Known pre-existing interstitial lung disease
• Significant or recent acute gastrointestinal disorders with diarrhoea as a a major symptoms.
• History or presence of clinically relevant cardiovascular abnormalities
• Cardiac left ventricular function with resting ejection fraction of less than 50%.
• Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
• Absolute neutrophil count(ANC)\<1500/mm3
• Platelet count\<100,000/mm3
• Creatinine clearance\<60ml/min or serum creatinine\>1.5 times Upper Limit of Normal (ULN).
• Bilirubin\>1.5 times ULN
• Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) \> 3 times ULN

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (36)

Beijing Chao-Yang Hospital

Beijing, 100020, China

Location

307 Hospital of PLA

Beijing, 100071, China

Location

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Beijing Chest Hospital

Beijing, 101149, China

Location

First Hospital of Jilin University

Changchun, 130021, China

Location

Xiangya Hospital, Central South University

Changsha, 410008, China

Location

Hunan Province Tumor Hospital

Changsha, China

Location

West China Hospital

Chengdu, 610041, China

Location

Fujian Provincial Tumor Hospital

Fuzhou, 350014, China

Location

Guangdong General Hospital

Guangzhou, 510080, China

Location

Guangzhou Institute of Respiratory Disease

Guangzhou, 510120, China

Location

NanFang Hosptial

Guangzhou, 510515, China

Location

The Third Affiliated Hospital of Harbin Medical University

Haerbin, 150081, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Hubei Cancer Hospital

Hongshan, China

Location

Yunnan Provincial Tumor Hospital

Kunming, 650118, China

Location

Lin Yi Tumor Hospital

Linyi, 276001, China

Location

the 81th Hospital of PLA

Nanjing, 210002, China

Location

Jiangsu Cancer Hospital

Nanjing, 210009, China

Location

The Affiliated Cancer Hospital, Guangxi Medical University

Nanning, China

Location

The affiliated hospital of medicalcollege qingdao university

Qingdao, 266101, China

Location

Shanghai Changzheng Hospital

Shanghai, 200003, China

Location

Shanghai Chest Hospital

Shanghai, 200030, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Changhai Hospital

Shanghai, 200443, China

Location

The First Hospital of Chinese Medical University

Shenyang, 110001, China

Location

Hebei Provincial Tumor Hospital

Shijiazhuang, China

Location

Tangdu Hospital

Xi'an, 710038, China

Location

Northern Jiangsu People's Hospital

Yangzhou, 225001, China

Location

Kosin University Gospel Hospital

Busan, 602-702, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, 361711, South Korea

Location

Yeungnam University Medical Center

Daegu, 705-717, South Korea

Location

Konkuk University Medical Center

Seoul, 143-729, South Korea

Location

Korea University Guro Hospital

Seoul, 152-703, South Korea

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Related Publications (7)

• Wu YL, Xu CR, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Marten A, Fan J, Peil B, Zhou C. Afatinib versus gemcitabine/cisplatin for first-line treatment of Chinese patients with advanced non-small-cell lung cancer harboring EGFR mutations: subgroup analysis of the LUX-Lung 6 trial. Onco Targets Ther. 2018 Nov 30;11:8575-8587. doi: 10.2147/OTT.S160358. eCollection 2018.

  PMID: 30584317 DERIVED

• Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, Lee KH, Tsai CM, Kato T, Barrios CH, Schuler M, Hirsh V, Yamamoto N, O'Byrne K, Boyer M, Mok T, Peil B, Marten A, Chih-Hsin Yang J, Paz-Ares L, Park K. Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 Trials. Clin Lung Cancer. 2018 Jul;19(4):e465-e479. doi: 10.1016/j.cllc.2018.03.009. Epub 2018 Mar 17.

  PMID: 29653820 DERIVED

• Yang JC, Sequist LV, Zhou C, Schuler M, Geater SL, Mok T, Hu CP, Yamamoto N, Feng J, O'Byrne K, Lu S, Hirsh V, Huang Y, Sebastian M, Okamoto I, Dickgreber N, Shah R, Marten A, Massey D, Wind S, Wu YL. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol. 2016 Nov;27(11):2103-2110. doi: 10.1093/annonc/mdw322. Epub 2016 Sep 6.

  PMID: 27601237 DERIVED

• Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. doi: 10.1016/j.jtho.2015.11.014. Epub 2016 Jan 25.

  PMID: 26823294 DERIVED

• Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4.

  PMID: 26051236 DERIVED

• Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. doi: 10.1016/S1470-2045(14)71173-8. Epub 2015 Jan 12.

  PMID: 25589191 DERIVED

• Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. doi: 10.1016/S1470-2045(13)70604-1. Epub 2014 Jan 15.

  PMID: 24439929 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Adenocarcinoma

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2010
• First Posted: May 12, 2010
• Study Start: April 19, 2010
• Primary Completion: November 23, 2017
• Study Completion: November 26, 2017
• Last Updated: December 14, 2018
• Results First Posted: January 26, 2015

Record last verified: 2018-12

Locations

CN (30); KR (5); TH (1)