Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

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

13. desember 2018 oppdatert av: Boehringer Ingelheim

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

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

364

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Kina
      • Beijing, Kina, 100071
        • 307 Hospital of PLA
      • Beijing, Kina, 100730
        • Peking Union Medical College Hospital
      • Beijing, Kina, 100020
        • Beijing Chao-Yang Hospital
      • Beijing, Kina, 101149
        • Beijing Chest Hospital
      • Changchun, Kina, 130021
        • First Hospital of Jilin University
      • Changsha, Kina, 410008
        • Xiangya Hospital, Central South University
      • Changsha, Kina
        • Hunan Province Tumor Hospital
      • Chengdu, Kina, 610041
        • West China Hospital
      • Fuzhou, Kina, 350014
        • Fujian Provincial Tumor Hospital
      • Guangzhou, Kina, 510080
        • Guangdong General Hospital
      • Guangzhou, Kina, 510120
        • Guangzhou Institute of Respiratory Disease
      • Guangzhou, Kina, 510515
        • NanFang Hosptial
      • Haerbin, Kina, 150081
        • The Third Affiliated Hospital of Harbin Medical University
      • Hangzhou, Kina, 310022
        • Zhejiang Cancer Hospital
      • HongShan, Kina
        • Hubei Cancer Hospital
      • Kunming, Kina, 650118
        • Yunnan Provincial Tumor Hospital
      • Linyi, Kina, 276001
        • Lin Yi Tumor Hospital
      • Nan Ning, Kina
        • The Affiliated Cancer Hospital, Guangxi Medical University
      • Nanjing, Kina, 210009
        • Jiangsu Cancer Hospital
      • Nanjing, Kina, 210002
        • the 81th Hospital of PLA
      • Qingdao, Kina, 266101
        • The affiliated hospital of medicalcollege qingdao university
      • Shanghai, Kina, 200030
        • Shanghai Chest Hospital
      • Shanghai, Kina, 200433
        • Shanghai Pulmonary Hospital
      • Shanghai, Kina, 200032
        • Zhongshan Hospital Fudan University
      • Shanghai, Kina, 200003
        • Shanghai Changzheng Hospital
      • Shanghai, Kina, 200443
        • Changhai Hospital
      • Shenyang, Kina, 110001
        • The First Hospital of Chinese Medical University
      • Shijiazhuang, Kina
        • Hebei Provincial Tumor Hospital
      • Xi'An, Kina, 710038
        • Tangdu Hospital
      • Yangzhou, Kina, 225001
        • Northern Jiangsu People's Hospital
  • Korea, Republikken
      • Busan, Korea, Republikken, 602-702
        • Kosin University Gospel Hospital
      • Cheongju, Korea, Republikken, 361711
        • Chungbuk National University Hospital
      • Daegu, Korea, Republikken, 705-717
        • Yeungnam University Medical Center
      • Seoul, Korea, Republikken, 143-729
        • Konkuk University Medical Center
      • Seoul, Korea, Republikken, 152-703
        • Korea University Guro Hospital
  • Thailand
      • Songkla, Thailand, 90110
        • Songklanagarind hospital

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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 Response Evaluation Criteria in Solid Tumours (RECIST)1.1
  4. Eastern Cooperative Oncology Group (ECOG) 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 International Conference on Harmonisation-Good Clinical Practice (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 Upper Limit of Normal (ULN).
  14. Bilirubin>1.5 times ULN
  15. Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Arm A BIBW 2992
Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity
Legemiddel: 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 Adverse Event (AE), dose reduction will be increments of 10 mg, with the lowest dose being 20mg.
Aktiv komparator: Arm B Chemotherapy
Patients receive Gemcitabine and Cisplatin, maximum is 6 courses
Legemiddel: Gemcitabine+Cisplatin
Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-free Survival
Tidsramme: 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

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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Objective Response (OR)
Tidsramme: 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

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.

(Exact 95% Confidence interval by Clopper and Pearson.)
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)
Tidsramme: 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
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.
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)
Tidsramme: From randomisation up to 374 weeks

OS is defined as the time from randomisation to death. For patients who had not died until 7 December 2017, 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.
From randomisation up to 374 weeks
Time to Objective Response (OR)
Tidsramme: 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

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.
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
Tidsramme: 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

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. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are 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 374
Duration of Disease Control
Tidsramme: 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
For patients with disease control, duration of disease control was defined as the time from randomisation to progression or death whichever occurs first. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are 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 374
Tumour Shrinkage
Tidsramme: 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

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.
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
Change From Baseline in Body Weight
Tidsramme: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
The change from baseline to the lowest and the last body weight recorded or during the the study.
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Tidsramme: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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.

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
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing
Tidsramme: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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. The median is Kaplan-Meier estimates.
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea
Tidsramme: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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. The median is Kaplan-Meier estimates.
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Health Related Quality of Life (HRQOL): Time of Deterioration in Pain
Tidsramme: Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.

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. The median is Kaplan-Meier estimates.
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Pharmacokinetics of Afatinib at Day 22
Tidsramme: Day 22 (course 2, visit 1)
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 Pharmacokinetics (PK) assessment period).
Day 22 (course 2, visit 1)
Pharmacokinetics of Afatinib at Day 29
Tidsramme: Day 29 (course 2, visit 2)
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).
Day 29 (course 2, visit 2)
Pharmacokinetics of Afatinib at Day 43
Tidsramme: Day 43 (course 3, visit 1)
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).
Day 43 (course 3, visit 1)
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events
Tidsramme: From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.
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.
From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.
Changes in Safety Laboratory Parameters
Tidsramme: From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.

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.
From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Boehringer Ingelheim

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

19. april 2010

Primær fullføring (Faktiske)

23. november 2017

Studiet fullført (Faktiske)

26. november 2017

Datoer for studieregistrering

Først innsendt

21. april 2010

Først innsendt som oppfylte QC-kriteriene

11. mai 2010

Først lagt ut (Anslag)

12. mai 2010

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

14. desember 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

13. desember 2018

Sist bekreftet

1. desember 2018

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 1200.34

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Kliniske studier på BIBW 2992

Søk i lignende forsøk

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

CROs by country

CROs in Dominican Republic

Forhold

Sjeldne sykdommer

Legemiddelintervensjoner

Kosttilskudd

Sponsor / samarbeidspartnere

Steder

3
Abonnere