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- Essai clinique NCT02171637
Dose Escalation Study of Oral Treatment With BIBW 2992 in Patients With Advanced Solid Tumors
20 juin 2014 mis à jour par: Boehringer Ingelheim
A Phase I Open Label Dose Escalation Study of Once-daily Oral Treatment With BIBW 2992 for 14 Days in Patients With Advanced Solid Tumors
Evaluation of maximum Tolerated Dose (MTD), safety, pharmacokinetics, efficacy of BIBW 2992, pharmacodynamic modulation of biomarkers, correlation of Epidermal Growth Factor Receptor (EGFR) and Human EGF-like Receptor number 2 (HER2) immunohistochemical status with objective tumour responses
Aperçu de l'étude
Type d'étude
Interventionnel
Inscription (Réel)
38
Phase
- La phase 1
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:
- Male or female patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumors, of types historically known to express EGFR and/or HER2, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
- Age 18 years or older
- Life expectancy of at least three (3) months
- Written informed consent given that is consistent with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines
- Eastern Cooperative Oncology Group (ECOG) performance score 0, 1, or 2
- Patients must have resolution of prior chemo-, hormone, immuno-, or radiotherapy-related toxicities to CTC Grade < 1
- Patients have to be recovered from previous surgery
- Paraffin-embedded tumor material must be accessible for analysis of EGFR and HER2-status.
- The additional 12 patients that were to be recruited at the MTD also had to fulfill the following criterion: Measurable tumor deposits (RECIST: Response Evaluation Criteria in Solid Tumors) by one or more techniques (X-ray, CT, MRI)
Exclusion Criteria:
- Active infectious disease
- Gastrointestinal disorders that might interfere with the absorption of the study drug or chronic diarrhea
- Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
- Brain metastases requiring therapy as based on clinical symptoms
- Impaired cardiac left ventricular function with resting ejection fraction CTC Grade ≥ 1
- Absolute neutrophil count (ANC) less than 1500 / mm3
- Platelet count less than 100 000 / mm3
- Bilirubin greater than 1.5 mg / dl (> 26 μmol / L, SI unit equivalent)
- Aspartate amino transferase (AST) and / 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)
- Serum creatinine greater than 1.5 mg / dl (> 132 μmol / L, SI (Systeme International) unit equivalent)
- Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
- Pregnancy or breast-feeding
- Treatment with other investigational drugs; chemotherapy, immunotherapy, radiotherapy or hormone therapy (excluding LHRH agonists, other hormones taken for breast cancer, or bisphosphonates) or participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
- Patients unable to comply with the protocol
- Active alcohol or drug abuse
RETREATMENT CRITERIA
The patient may be eligible for re-treatment after the previous course finished. The patient will not be eligible if the following criteria are met.
- Patients with clinical signs of disease progression or if an X-ray, CT or MRI was done and the test showed progressive disease
- Cardiac left ventricular function CTC Grade ≥ 2 at any time during the previous course
- Patients fulfilling any of the Exclusion Criteria as mentioned under exclusion criteria on Day 29 of the previous course
- Patients not recovered from any dose-limiting toxicity (DLT) 14 days after the last administration of BIBW 2992 in the previous course. Recovery is defined as a return to baseline level or CTC Grade 1, whichever is higher
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
|
escalating doses
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
---|---|
Maximum tolerated dose (MTD)
Délai: up to 28 months
|
up to 28 months
|
Incidence and intensity of Adverse Events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) associated with increasing doses of BIBW 2992
Délai: up to 28 months
|
up to 28 months
|
Mesures de résultats secondaires
Mesure des résultats |
Délai |
---|---|
Area under the plasma concentration-time curve (AUC) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Predose plasma concentration (Cpre) for different time points
Délai: Day 8 and 14
|
Day 8 and 14
|
Minimum measured plasma concentration (Cmin) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Maximum measured plasma concentration (Cmax) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Time from dosing to the minimum plasma concentration (tmin) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Time from dosing to the maximum plasma concentration (tmax) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Terminal half-life (t1/2) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Mean residence time after oral administration (MRTpo) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Apparent clearance (CL/F) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Apparent volume of distribution during the terminal phase (Vz/F) for different time points
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Accumulation ratio (RA)
Délai: up to 384 hours after first drug administration
|
up to 384 hours after first drug administration
|
Modulation of biomarker (EGFR, p-EGFR, p-MAPK (mitogen-activated protein kinase), p-Akt, Ki-67, p-27KIP1) in skin biopsies prior to administration of BIBW 2992 and at the end of the first treatment period
Délai: Baseline and day 14
|
Baseline and day 14
|
Modulation of biomarker (EGFR, p-EGFR, HER2, p-MAPK, p-Akt, Ki-67, p-27KIP1) in tumor biopsies prior to administration of BIBW 2992 and at the end of the first treatment period in 6 or more patients treated at the MTD
Délai: Baseline and day 14
|
Baseline and day 14
|
Objective tumor responses
Délai: every 8 weeks up to 28 months
|
every 8 weeks up to 28 months
|
Correlation of EGFR, HER2, estrogen receptor and progesterone receptor immunohistochemical status as based on tumor biopsies or excisions obtained prior to this trial with objective tumor responses
Délai: up to 28 months
|
up to 28 months
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
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.
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 novembre 2003
Achèvement primaire (Réel)
1 février 2006
Dates d'inscription aux études
Première soumission
20 juin 2014
Première soumission répondant aux critères de contrôle qualité
20 juin 2014
Première publication (Estimation)
24 juin 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
24 juin 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
20 juin 2014
Dernière vérification
1 juin 2014
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 1200.1
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 .
Essais cliniques sur BIBW 2992
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Boehringer IngelheimComplété
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Boehringer IngelheimComplété
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Boehringer IngelheimComplétéTumeurs mammairesÉtats-Unis, Royaume-Uni
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Centre Leon BerardBoehringer IngelheimComplétéCarcinome épidermoïde de la tête et du couFrance
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Boehringer IngelheimComplété
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Boehringer IngelheimComplété
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Boehringer IngelheimApprouvé pour la commercialisationCarcinome pulmonaire non à petites cellulesAustralie
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Boehringer IngelheimComplété
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Medical University of South CarolinaBoehringer IngelheimRetiré
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Boehringer IngelheimComplété