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Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

4 septembre 2015 mis à jour par: Boehringer Ingelheim

A Phase Ib Open Label Clinical Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 Plus Sirolimus in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib

The primary objective of this trial is to identify the Maximum Tolerated Dose of BIBW 2992 therapy when given continuously in combination with Sirolimus.

The MTD will be based on the Dose Limiting Toxicity information collected during the first two cycles.

Overall safety, pharmacokinetics and anti-tumour efficacy will be evaluated as secondary objectives.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

44

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Espagne
      • Badalona (Barcelona), Espagne
        • 1200.70.34001 Boehringer Ingelheim Investigational Site
      • Barcelona, Espagne
        • 1200.70.34008 Boehringer Ingelheim Investigational Site
      • Barcelona, Espagne
        • 1200.70.34009 Boehringer Ingelheim Investigational Site
      • Girona, Espagne
        • 1200.70.34006 Boehringer Ingelheim Investigational Site
      • L'Hospitalet de Llobregat (Barcelona), Espagne
        • 1200.70.34007 Boehringer Ingelheim Investigational Site
      • Majadahonda (Madrid), Espagne
        • 1200.70.34005 Boehringer Ingelheim Investigational Site
      • Valencia, Espagne
        • 1200.70.34004 Boehringer Ingelheim Investigational Site
      • Zaragoza, Espagne
        • 1200.70.34002 Boehringer Ingelheim Investigational Site

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion criteria:

  1. Pathologically or cytologically confirmed diagnosis of Stage IIIB or Stage IV NSCLC
  2. Patients who have failed conventional treatment (at least 1 prior treatment line), or for whom no therapy of proven efficacy exists

  3. Patients whose tumors:

    • are EGFR mutation-positive or
    • are EGFR mutation-negative or unknown provided they had disease progression after achieving either response or stable disease for at least 6 months from a previous treatment with erlotinib (Tarceva®) or gefitinib (Iressa®)
  4. Patients aged 18 years or older
  5. Life expectancy of at least three (3) months
  6. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0-2
  7. Written informed consent that is consistent with ICH-GCP guidelines

Exclusion criteria:

  1. Prior major surgery, chemotherapy or radiation therapy within 4 weeks before start of therapy.
  2. Prior treatment with an mTOR inhibitor within the past 4 weeks before start of therapy or concomitantly with this study
  3. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of run-in treatment with Sirolimus
  4. Active CNS metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants or steroids)
  5. Severe alteration in serum fasting cholesterol (equal or more than 350 mg/dL) or triglycerides (equal or more than 400 mg/dL). Patients may be allowed to enrol on the trial after initiation of lipid lowering agents.

  6. Requirement for treatment with any of the prohibited concomitant medications:

    • Concomitant CYP3A4 inhibitors within the past 7 days before start of therapy or concomitantly with this study.
    • Concomitant CYP3A4 inducers within the past 14 days before start of therapy or concomitantly with this study.
  7. Any contraindications for therapy with Sirolimus.
  8. Known hypersensitivity to BIBW 2992, Sirolimus or other rapamycin analogues (everolimus, temsirolimus, deforolimus, etc.) or the excipients of any of the trial drugs.
  9. Use of any investigational drug within 4 weeks before start of therapy.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: BIBW 2992 + Sirolimus
Dose escalation of the combination BIBW 2992 plus Sirolimus.
Médicament: BIBW 2992
Dose escalation (19-40 patients): low or high dose oral + 12 addit. pat. at MTD, until progression or undue AEs
Médicament: Sirolimus (rapamycin)
Dose escalation (19-40 patients): several dose levels + 12 addit. pat. at MTD until progression or undue AEs.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Occurrence of Dose Limiting Toxicities (DLT)
Délai: 2 first cycles, 56 days
Number of participants with of dose limiting toxicities (DLT)
2 first cycles, 56 days

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Best Overall Response
Délai: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Best overall response (unconfirmed) according to RECIST v1.1
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Objective Response
Délai: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Rate of (unconfirmed) objective response, defined as complete response (CR) or partial response (PR) according to RECIST v1.1
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Rate of Disease Control
Délai: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Rate of (unconfirmed) disease control defined as CR, PR, or stable disease (SD), according to RECIST v1.1
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA.
Délai: Multiple time points during the trial

Exploratory examination of Epidermal growth factor (receptor)(EGFR) mutations (Exons 19, 20 and 21 and others) in serum/plasma DNA and tumour DNA.

This endpoint was not analysed in the study report as the available data was too limited.
Multiple time points during the trial
Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss)
Délai: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
Maximum measured plasma concentration of Afatinib at steady state (Cmax,ss)
24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss)
Délai: 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
Area under the curve (AUC) of Afatinib at steady state over the dosing interval τ (AUCτ,ss) for afatinib.
24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib
Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss)
Délai: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
Maximum measured plasma concentration of sirolimus at steady state (Cmax,ss)
24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss)
Délai: 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
Area under the curve (AUC) of sirolimus at steady state over the dosing interval τ (AUCτ,ss) for afatinib.
24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib
Occurrence of Adverse Events According to CTCAE, Version 3.0
Délai: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Percentage of participants with adverse events according to highest Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Percentage of Patients With Drug-related AEs
Délai: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Percentage of patients with drug-related adverse events (AEs).
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin
Délai: From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days
Evaluation of laboratory parameters included assessment of the frequency of patients with ALT and AST elevations concurrent with elevated bilirubin and indicative of Hy's law cases.
From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Boehringer Ingelheim

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 octobre 2009

Achèvement primaire (Réel)

1 septembre 2014

Achèvement de l'étude (Réel)

1 septembre 2014

Dates d'inscription aux études

Première soumission

8 octobre 2009

Première soumission répondant aux critères de contrôle qualité

9 octobre 2009

Première publication (Estimation)

12 octobre 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

7 octobre 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité

4 septembre 2015

Dernière vérification

1 septembre 2015

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 1200.70
  • 2009-010432-18 (Numéro EudraCT: EudraCT)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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