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LUX Lung 2 Phase II Single Arm BIBW 2992 "Afatinib" in NSCLC With EGFR Activating Mutations

28 de julho de 2016 atualizado por: Boehringer Ingelheim

LUX Lung 2 A Phase II Single-arm Trial of BIBW 2992 in Non-small Cell Lung Cancer Patients With EGFR Activating Mutations

The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by RECIST criteria in patients with advanced NSCLC Stage IIIB or IV whose tumors harbor activating mutations within exon 18 to exon 21 of the EGFR receptor. Patients progressing or relapsing after one prior cytotoxic chemotherapy regimen as well as chemotherapy naïve patients (only in stage 2) will be allowed to enter into the trial.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

129

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Estados Unidos
    • California
      • Bakersfield, California, Estados Unidos
        • 1200.22.28 Boehringer Ingelheim Investigational Site
      • Beverly Hills, California, Estados Unidos
        • 1200.22.32 Boehringer Ingelheim Investigational Site
      • Mission Hills, California, Estados Unidos
        • 1200.22.4 Boehringer Ingelheim Investigational Site
      • Orange, California, Estados Unidos
        • 1200.22.16 Boehringer Ingelheim Investigational Site
    • Florida
      • Fort Lauderdale, Florida, Estados Unidos
        • 1200.22.19 Boehringer Ingelheim Investigational Site
      • North Miami Beach, Florida, Estados Unidos
        • 1200.22.29 Boehringer Ingelheim Investigational Site
    • Georgia
      • Atlanta, Georgia, Estados Unidos
        • 1200.22.10 Boehringer Ingelheim Investigational Site
    • Illinois
      • Chicago, Illinois, Estados Unidos
        • 1200.22.18 Boehringer Ingelheim Investigational Site
    • Maryland
      • Bethesda, Maryland, Estados Unidos
        • 1200.22.3 Boehringer Ingelheim Investigational Site
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos
        • 1200.22.14 Boehringer Ingelheim Investigational Site
    • Michigan
      • Flint, Michigan, Estados Unidos
        • 1200.22.24 Boehringer Ingelheim Investigational Site
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos
        • 1200.22.5 Boehringer Ingelheim Investigational Site
    • New York
      • New York, New York, Estados Unidos
        • 1200.22.15 Boehringer Ingelheim Investigational Site
      • New York, New York, Estados Unidos
        • 1200.22.26 Boehringer Ingelheim Investigational Site
      • Rochester, New York, Estados Unidos
        • 1200.22.1 Boehringer Ingelheim Investigational Site
      • Syracuse, New York, Estados Unidos
        • 1200.22.27 Boehringer Ingelheim Investigational Site
      • Valhalla, New York, Estados Unidos
        • 1200.22.25 Boehringer Ingelheim Investigational Site
    • Ohio
      • Canton, Ohio, Estados Unidos
        • 1200.22.6 Boehringer Ingelheim Investigational Site
    • Pennsylvania
      • Wynnewood, Pennsylvania, Estados Unidos
        • 1200.22.7 Boehringer Ingelheim Investigational Site
    • South Carolina
      • Mt. Pleasant, South Carolina, Estados Unidos
        • 1200.22.22 Boehringer Ingelheim Investigational Site
    • Virginia
      • Fairfax, Virginia, Estados Unidos
        • 1200.22.31 Boehringer Ingelheim Investigational Site
    • Washington
      • Renton, Washington, Estados Unidos
        • 1200.22.40 Boehringer Ingelheim Investigational Site
      • Seattle, Washington, Estados Unidos
        • 1200.22.33 Boehringer Ingelheim Investigational Site
  • Taiwan
      • Taichung, Taiwan
        • 1200.22.88604 Taichung Veterans General Hospital
      • Taichung, Taiwan
        • 1200.22.88605 China Medical University Hospital
      • Tainan, Taiwan
        • 1200.22.88606 Boehringer Ingelheim Investigational Site
      • Taipei, Taiwan
        • 1200.22.88601 National Taiwan University Hospital
      • Taipei, Taiwan
        • 1200.22.88602 Veterans General Hospital
      • Taipei City, Taiwan
        • 1200.22.88607 Boehringer Ingelheim Investigational Site
      • Taoyuan, Taiwan
        • 1200.22.88603 Chang Gung Memorial Hosp-Linkou

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 99 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion criteria:

  1. Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with pleural effusion) adenocarcinoma or Stage IV adenocarcinoma.
  2. Presence of activating mutation(s) in exon 18 to exon 21 of the EGFR-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue.
  3. Progressive disease following a first line cytotoxic chemotherapy regimen or have recurrent disease after prior neoadjuvant or adjuvant chemotherapy. Patients who have not received first-line cytotoxic chemotherapy can be enrolled in stage 2 of the trial, if the criteria for entering stage 2 are met.
  4. Patients with at least one tumor lesion that can accurately be measured by computed tomography (CT) or magnetic resonance imaging (MRI) in at least one dimension with longest diameter to be recorded as 20 mm using conventional techniques or 10 mm with spiral CT scan.
  5. Male or female patient aged 18 years.
  6. Life expectancy of at least three (3) months.
  7. Written informed consents that is consistent with ICH-GCP guidelines.
  8. Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.

Exclusion criteria:

  1. More than one (1) prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC.
  2. Chemo-, hormone- (other than Megace®) or immunotherapy within the past 4 weeks or within less than four half-lives of the previous drug prior to treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant.
  3. Previous treatment with erlotinib (Tarceva®), gefitinib (Iressa®) or any other EGFR inhibiting small molecule or antibody.
  4. Brain metastases, which are symptomatic; patients with treated, asymptomatic brain metastases are eligible with stable brain disease for at least four (4) weeks without the requirement for steroids or anti-epileptic therapy.
  5. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohns disease, malabsorption, or CTCAE Grade >2 diarrhea of any etiology at baseline.
  6. Patients who have any other life-threatening 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.
  7. Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
  8. Radiotherapy within the past 2 weeks prior to treatment with the trial drug.
  9. Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents).
  10. Patients with known HIV, active hepatitis B or active hepatitis C.
  11. Known or suspected active drug or alcohol abuse.
  12. Women of child-bearing potential or men who are able to father a child unwilling to use a medically acceptable method of contraception during the trial.
  13. Pregnancy or breast feeding.
  14. Patient unable to comply with the protocol.
  15. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3.
  16. Cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram.
  17. QTc interval greater than 0.47 second.
  18. Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) greater than 400 mg/m2.
  19. Absolute neutrophil count (ANC) less than 1500/mm3.
  20. Platelet count less than 100 000 /mm3.
  21. Bilirubin greater than 1.5 mg / dl (greater than 26 micromol / L, SI unit equivalent).
  22. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal).
  23. Serum creatinine greater than 1.5 times of the upper normal limit or calculated/measured creatinine clearance equal or less than 45 ml / min.
  24. Patients with known pre-existing interstitial lung disease

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: BIBW 2992
Patients start continuous once daily oral treatment of BIBW 2992 at high dose, until progression or undue Adverse Events (AEs) develop. Patients can be dose-reduced up to two times if needed after temporary discontinuation of treatment due to drug-related AEs. After protocol amendment 2 (17 Dec 2008), the starting dose of BIBW 2992 was reduced to a medium dose, with 2 possible dose reductions if needed after discontinuation due to drug-related AEs.
Medicamento: BIBW 2992
This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Objective Response (OR) as Determined by RECIST 1.0
Prazo: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Objective response (OR) was assessed for all treated patients by independent review as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. OR included complete response (CR) and partial response (PR), where CR or PR must have been confirmed by a subsequent response in ≥28 days.
Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Clinical Benefit as Determined by RECIST 1.0
Prazo: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Clinical benefit was evaluated according to RECIST 1.0 by independent review assessment. Patients whose best RECIST 1.0 assessment was stable disease (SD), partial response (PR), or complete response (CR) were considered to have derived a clinical benefit from treatment.
Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Duration of Clinical Benefit
Prazo: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Duration of clinical benefit (disease control) as per independent review was defined as the time from the start of treatment to the time of progression or death (whichever occurred first), among patients with evidence of SD, PR or CR.
Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Duration of Objective Response
Prazo: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Duration of objective response (OR) was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death (or date of censoring for PFS) was objectively documented as per independent review.
Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Time to Objective Response
Prazo: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

Time to objective response was defined as the number of days from the start of treatment to the first recorded objective response. Patients who did not experience objective response during the study were censored at the time of treatment discontinuation.

The results are provided as the percentage of participants for this Outcome Measure.
Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Progression-free Survival
Prazo: Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Progression-free survival (PFS) as per independent review was defined as the duration of time from the start of treatment until the day of objective tumor progression was confirmed by tumor imaging (Progressive Disease according to RECIST 1.0) or death, whichever came first. Patients with unknown progression status or unknown date of progression were reviewed on a case-by-case basis. Patients known to be alive without progression at the end of the trial or the last follow-up visit were censored at the date of the last imaging when the patient was known to be alive and progression-free. Medians are calculated from the Kaplan-Meier estimates and 95% confidence intervals, using Greenwood's standard error estimate.
Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.
Overall Survival Time
Prazo: Start of treatment to time to all death, up to 93 months
Overall survival time (OS) was also evaluated and was defined as the duration of time from start of treatment to time of death up to 93 months, regardless of the cause of death. Medians are calculated from the Kaplan-Meier estimates and 95% confidence intervals, using Greenwood's standard error estimate.
Start of treatment to time to all death, up to 93 months
Cpre,ss,29
Prazo: -0:05h (pre-dose) on Day 29
Predose concentration of the analyte in plasma at steady state immediately before administration of the 29th dose (Cpre,ss,29).
-0:05h (pre-dose) on Day 29
Safety of BIBW 2992 as Indicated by Incidence of Specified Adverse Events.
Prazo: First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
Safety of afatinib as indicated by incidence of specified adverse events: skin reactions (a preferred term of the system organ class: Skin and subcutaneous tissue disorders) and gastrointestinal (GI) (a system organ class).
First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
Safety of BIBW 2992 as Indicated by Intensity and Incidence of Worst Adverse Events Graded According to NCI CTCAE Version 3.0
Prazo: First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
Safety of afatinib as indicated by intensity and incidence of worst adverse events graded according to National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) Version 3.0 (R04-0474).
First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Boehringer Ingelheim

Publicações e links úteis

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Publicações Gerais

Links úteis

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de agosto de 2007

Conclusão Primária (Real)

1 de fevereiro de 2010

Conclusão do estudo (Real)

1 de agosto de 2015

Datas de inscrição no estudo

Enviado pela primeira vez

3 de setembro de 2007

Enviado pela primeira vez que atendeu aos critérios de CQ

3 de setembro de 2007

Primeira postagem (Estimativa)

5 de setembro de 2007

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

16 de setembro de 2016

Última atualização enviada que atendeu aos critérios de controle de qualidade

28 de julho de 2016

Última verificação

1 de julho de 2016

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 1200.22

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