Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer (SELECT-3)
12 mars 2018 mis à jour par: AstraZeneca
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)
This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.
This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)
Type d'étude
Interventionnel
Inscription (Réel)
55
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
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Glasgow, Royaume-Uni, G12 0YN
- Research Site
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London, Royaume-Uni, W1G 6AD
- Research Site
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Manchester, Royaume-Uni, M20 4BX
- Research Site
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Newcastle upon Tyne, Royaume-Uni, NE7 7DN
- Research Site
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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 à 99 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Provision of signed, written and dated consent prior to any study specific procedures
- Male or female, aged 18 years or older
- Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
- Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
- Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information
Exclusion Criteria:
- Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
- Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
- Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
- Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection
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 |
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Expérimental: Selumetinib+standard chemotherapy
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
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2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin).
If tolerated - next cohort 3 x 25mg capsules bd continuously.
if higher doses are explored, required number of capsules will be provided.
Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy
1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle.
If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
75 mg/m2 iv on Day 1 of each 21 day cycle.
If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle
Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
Délai: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
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Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
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The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Best Objective Response
Délai: Screening, week 6 and week 12
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The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression.
Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm
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Screening, week 6 and week 12
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Percentage Change From Baseline at 6 Weeks in Target Lesion Size
Délai: Week 6
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The percentage change in the sum of the diameters of target lesions
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Week 6
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Best Percentage Change From Baseline in Target Lesion Size
Délai: Screening, week 6 and week 12
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The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression.
Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
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Screening, week 6 and week 12
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Objective Response Rate (ORR)
Délai: Up until progression or last evaluable assessment in the absence of progression, up to 9 months
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The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression.
Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
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Up until progression or last evaluable assessment in the absence of progression, up to 9 months
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AUC (0-tau)
Délai: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Cmax,ss
Délai: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Maximum plasma concentration at steady state
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Tmax,ss
Délai: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Time to reach maximum plasma concentration at steady state
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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CL/F
Délai: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Apparent oral plasma clearance
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Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Directeur d'études: Gabriella Mariani, MD, AstraZeneca UK, MSD
- Chercheur principal: Emma Dean, BMEDSCI, BM, BS, PHD, The Christie NHS Foundation Trust, UK
- Chercheur principal: Fiona Blackhall, PhD, FRCP, The Christie NHS Foundation Trust Clinical Trials Unit; UK
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 (Réel)
4 avril 2013
Achèvement primaire (Réel)
4 janvier 2016
Achèvement de l'étude (Réel)
4 janvier 2016
Dates d'inscription aux études
Première soumission
8 mars 2013
Première soumission répondant aux critères de contrôle qualité
11 mars 2013
Première publication (Estimation)
12 mars 2013
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
13 mars 2018
Dernière mise à jour soumise répondant aux critères de contrôle qualité
12 mars 2018
Dernière vérification
1 mars 2018
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies des voies respiratoires
- Tumeurs
- Maladies pulmonaires
- Tumeurs par site
- Tumeurs des voies respiratoires
- Tumeurs thoraciques
- Carcinome bronchique
- Tumeurs bronchiques
- Tumeurs pulmonaires
- Carcinome pulmonaire non à petites cellules
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs de la synthèse des acides nucléiques
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Antagonistes de l'acide folique
- Gemcitabine
- Carboplatine
- Cisplatine
- Pémétrexed
Autres numéros d'identification d'étude
- D1532C00070
- EudraCT number: 2012-005202-22
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