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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01121393
First received: April 21, 2010
Last updated: July 19, 2016
Last verified: July 2016

April 21, 2010
July 19, 2016
April 2010
December 2013   (final data collection date for primary outcome measure)
Progression-free Survival [ Time Frame: 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 ] [ Designated as safety issue: No ]

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.

Progression-free Survival [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01121393 on ClinicalTrials.gov Archive Site
  • Objective Response (OR) [ Time Frame: 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 ] [ Designated as safety issue: No ]

    OR is defined as a best overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with OR.

    CR is defined as the disappearance of all target lesions and non-target lesions and no new lesions.

    PR is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD, non-Progressive Disease or non evaluation of all non-target lesions and no new lesions.

    Only data collected up until the analysis cut-off date (27 December 2013) were considered.

    (Exact 95% Confidence interval by Clopper and Pearson.)

  • Disease Control (DC) [ Time Frame: 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 ] [ Designated as safety issue: No ]

    DC is defined as a patient with objective response (OR) or stable disease (SD) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with DC.

    Only data collected up until the analysis cut-off date (27 December 2013) were considered.

  • Overall Survival (OS) [ Time Frame: From randomisation up to 27 Dec. 2013 cut off date for this analysis ] [ Designated as safety issue: No ]

    OS is defined as the time from randomisation to death. For patients who had not died by the cut-off date (27 Dec 2013), the date they were last known to be alive was derived from patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date.

    Median time results from unstratified Kaplan-Meier estimates.

  • Time to Objective Response (OR) [ Time Frame: 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 ] [ Designated as safety issue: No ]

    OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1.

    For patients with an objective response, time to objective response was defined as the time from randomisation to the first objective response.

    Outcome data are the percentage of patients with OR by each scheduled tumour assessment.

    Only data collected up until the analysis cut-off date (27 December 2013) were considered.

  • Duration of Objective Response [ Time Frame: 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 ] [ Designated as safety issue: No ]

    OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1.

    For patients with an objective response, duration of objective response was defined as the time from the first objective response to disease progression or death whichever occurs earlier. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered.

    A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.

  • Duration of Disease Control [ Time Frame: 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 ] [ Designated as safety issue: No ]

    For patients with disease control, duration of disease control was defined as the time from randomisation to progression or death whichever occurs first. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered.

    A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.

  • Tumour Shrinkage [ Time Frame: 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 ] [ Designated as safety issue: No ]

    Tumour shrinkage is calculated as the minimum post-baseline sum of longest diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) (SLD), as assessed by central independent review. The mean of these minimum values are presented after adjusting for baseline sum of longest diameters and EGFR mutation category. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered. A negative value means the smallest post-baseline SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline.

    The means are adjusted for baseline sum of lesions and EGFR mutation category.

  • Change From Baseline in Body Weight [ Time Frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months. ] [ Designated as safety issue: No ]
    The change from baseline to the lowest and the last body weight recorded or during the the study. Only data collected up until the analysis cut-off date (27 December 2013) were considered.
  • Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [ Time Frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months. ] [ Designated as safety issue: No ]

    The last ECOG performance score category recorded during the study. Outcome data are the percentage of patients with an shift of ECOG performance status from baseline to the last ECOG performance status.

    Only data collected up to the analysis cut-off date (27 December 2013) were considered.

    ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction;

    1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work;
    2. Ambulatory (>50 percent of waking hours), capable of all selfcare, unable to carry out any work activities;
    3. Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours;
    4. Completely disabled, cannot carry on any selfcare, totally confined to bed or chair;
    5. Dead
  • Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing [ Time Frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months. ] [ Designated as safety issue: No ]

    HRQOL as measured by standardised questionnaires (EuropeanOrganisation for Research and Treatment of Cancer (EORTC)) quality of life questionaires (OLQ-C30) and its lung cancer module (QLQ-LC13). Analysis for cough: QLQ-LC13, question 1.

    Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered.

    The median is Kaplan-Meier estimates.

  • Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea [ Time Frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months. ] [ Designated as safety issue: No ]

    HRQOL as measured by OLQ-C30 and its lung cancer module (QLQ-LC13). Analysis for dyspnoea: composite of QLQ-LC13, questions 3 to 5; individual item from QLQ-C30, question 8.

    Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered. The median is Kaplan-Meier estimates.

  • Health Related Quality of Life (HRQOL): Time of Deterioration in Pain [ Time Frame: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 42 months. ] [ Designated as safety issue: No ]

    HRQOL as measured by OLQ-C30 and its lung cancer module QLQ-LC13. Analysis for pain: composite of QLQ-C30, questions 9 and 19; individual items from QLQ-LC13, questions 10, 11 and 12.

    Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered.

    The median is Kaplan-Meier estimates.

  • Pharmacokinetics of Afatinib at Day 22 [ Time Frame: Day 22 (course 2, visit 1) ] [ Designated as safety issue: No ]
    Outcome data are the trough plasma concentrations of afatinib at day 22 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).
  • Pharmacokinetics of Afatinib at Day 29 [ Time Frame: Day 29 (course 2, visit 2) ] [ Designated as safety issue: No ]
    Outcome data are the trough plasma concentrations of afatinib at day 29 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).
  • Pharmacokinetics of Afatinib at Day 43 [ Time Frame: Day 43 (course 3, visit 1) ] [ Designated as safety issue: No ]
    Outcome data are the trough plasma concentrations of afatinib at day 43 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).
  • Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events [ Time Frame: From first administration of study medication up to 28 days after the last administration of study medication up to 42.2 months ] [ Designated as safety issue: No ]

    Safety of Afatinib as indicated by intensity and incidence of adverse events graded according to the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Presented as the percentage of patients with an Adverse Events during the on-treatment period by highest CTCAE grade.

    Only data collected up to the analysis cut-off date (27 December 2013) were considered.

  • Changes in Safety Laboratory Parameters [ Time Frame: From first administration of study medication up to 28 days after the last administration of study medication up to 42.2 months ] [ Designated as safety issue: No ]

    Outcome data presented are the percentage of patients by worst CTCAE grade (only Grades 2 to 4 presented) on treatment for the following laboratory parameters: Potassium, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine and Creatine Kinase.

    For Potassium; only CTCAE grades resulting from hypokalemia (low values) are presented.

    Only data collected up to the analysis cut-off date (27 December 2013) were considered.

  • Complete Response, Partial Response, Stable Disease, Progressive Disease according to RECIST1.1 [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: every 21 days ] [ Designated as safety issue: No ]
  • deterioration of body weight and ECOG performance status [ Time Frame: every 21 days ] [ Designated as safety issue: No ]
  • score change of questionnaires health-related quality of life [ Time Frame: every 21 days ] [ Designated as safety issue: No ]
  • pharmacokinetics of BIBW 2992(detect the valley concentration of BIBW 2992) [ Time Frame: day 1, 8 of cycle 2, day 1 of cycle 3 ] [ Designated as safety issue: No ]
  • safety of BIBW 2992 as indicated by intensity and incidence of adverse events [ Time Frame: every 21 days ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)
LUX-Lung 6: A Randomized, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
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
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Carcinoma, Non-Small-Cell Lung
  • Adenocarcinoma
  • Drug: Gemcitabine+Cisplatin
    Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.
  • Drug: BIBW 2992
    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 AE, dose reduction will be increments of 10 mg, with the lowest dose being 20mg.
  • Experimental: Arm A BIBW 2992
    Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity
    Intervention: Drug: BIBW 2992
  • Active Comparator: Arm B Chemotherapy
    Patients receive Gemcitabine and Cisplatin, maximum is 6 courses
    Intervention: Drug: Gemcitabine+Cisplatin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
364
December 2016
December 2013   (final data collection date for primary outcome measure)

Inclusion criteria:

  1. pathologically confirmed diagnosis of stage IIIB or stage IV adenocarcinoma of the Lung
  2. EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory analysis of tumor biopsy material
  3. Measurable disease according to RECIST1.1
  4. ECOG(Eastern Cooperative Oncology Group) score of 0 or 1.
  5. Age>=18 years
  6. life expectancy of at least three months
  7. Written informed consent that is consistent with ICH-GCP guidelines.

Exclusion criteria:

  1. Prior chemotherapy for relapsed and/or metastatic NSCLC.
  2. Prior treatment with EGFR targeting small molecules or antibodies.
  3. Radiotherapy or surgery(other than biopsy) within 4 weeks prior to randomization
  4. Active brain metastases
  5. Any other current malignancy or malignancy diagnosed within the past 5 years
  6. Known pre-existing interstitial lung disease
  7. Significant or recent acute gastrointestinal disorders with diarrhoea as a a major symptoms.
  8. History or presence of clinically relevant cardiovascular abnormalities
  9. Cardiac left ventricular function with resting ejection fraction of less than 50%.
  10. 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.
  11. Absolute neutrophil count(ANC)<1500/mm3
  12. Platelet count<100,000/mm3
  13. Creatinine clearance<60ml/min or serum creatinine>1.5 times ULN(upper limiter of number).
  14. Bilirubin>1.5 times ULN
  15. AST(Aspartate Amino Transferase) or ALT(Alanine Amino Transferase) > 3 times ULN
  16. Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial
  17. Pregnancy of breast-feeding
  18. Patients unable to comply with the protocol
  19. Active hepatitis B infection, active hepatitis C infection or known HIV(Human Immunodeficiency Virus) carrier.
  20. Known or suspected active drug or alcohol abuse.
  21. requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2
  22. Any contraindications for therapy with gemcitabine/cisplatin
  23. Known hypersensitivity to BIBW2992 or the excipient of any of the trial drugs
  24. Use of any investigational drug within 4 weeks of randomization.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
China,   Korea, Republic of,   Thailand
India
 
NCT01121393
1200.34
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP