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Combination Study of GSK1120212 With Gemcitabine in Subjects With Solid Tumors

8 novembre 2017 mis à jour par: GlaxoSmithKline

A Phase IB Combination Study of MEK Inhibitor GSK1120212 With Gemcitabine in Subjects With Solid Tumors

MEK112111 is a dose-escalation, Phase IB, open-label, single-arm, multi-center study. The primary objective of the study is to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with gemcitabine in subjects with solid tumors.

Aperçu de l'étude

Statut

Complété

Description détaillée

Subjects will be enrolled using a dose-escalation procedure in which the initial cohort receives a fraction of the GSK1120212 dose that achieved a dose limiting toxicity in a previous study and the recommended dose of gemcitabine. Escalation will proceed until the maximum tolerated doses are identified. These doses will be selected based on emerging safety data. Confirmation of the tolerability of the Recommended Phase II Dose (RP2D) will be explored in approximately 12 subjects. Subjects will continue on treatment until treatment discontinuation criteria are met (disease progression, intercurrent illness, adverse event or consent withdrawal).

Type d'étude

Interventionnel

Inscription (Réel)

31

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

    • Tennessee
      • Nashville, Tennessee, États-Unis, 37203
        • GSK Investigational Site
    • Texas
      • San Antonio, Texas, États-Unis, 78229
        • GSK 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:

  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Age 18 years old or older and able to swallow oral medication.
  • Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology (ECOG) scale.
  • Histologically or cytologically confirmed diagnosis of a solid tumor malignancy that is either relapsed or refractory, or potentially responsive to gemcitabine.
  • Tumor Type criteria as listed in protocol.
  • Male subjects must agree to use one of the contraception methods listed in protocol.
  • A female subject is eligible to participate if she is of non-childbearing potential as defined in the protocol or postmenopausal as defined in the protocol. If of child-bearing potential, she agrees to use protocol specified contraceptive methods
  • Adequate organ system function as defined below in the protocol.

Exclusion Criteria:

  • Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of GSK1120212.
  • Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is shorter preceding the first dose of GSK1120212 - as long as a minimum of 14 days has passed between the last dose of the prior investigational anti-cancer drug and the first dose of GSK1120212.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, dimethy sulfoxide (DMSO), or excipients (See protocol)
  • Use of a prohibited medication (as defined in protocol) or current use of anticoagulants (e.g. warfarin, heparin, low molecular weight heparin) at therapeutic levels. Low dose (prophylactic) anticoagulants are permitted provided that subject's prothrombin time (PT) and partial thromboplastin time (PTT) meet entry criteria.
  • Gastrointestinal disease predicted to interfere with absorption of an oral drug.
  • History of retinal vein occlusion (RVO) or central serous retinopathy.
  • Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis.
  • Glaucoma diagnosed within one month prior to study day 1.
  • Intraocular pressure > 21mm Hg as measured by tonography.
  • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Subjects previously treated for these conditions that are asymptomatic and off corticosteroids for at least two months are permitted. Subjects are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs).
  • Unresolved toxicity greater than common terminology criteria for adverse events (CTCAE v4.0) grade 1 from previous anti-cancer therapy.
  • History of acute coronary within the past 24 weeks.
  • QTc interval greater than or equal to 480 mili seconds (msecs).
  • Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Pregnant or lactating female.
  • History of hepatitis B or C. NOTE: Subjects with evidence of cleared hepatitis B infection are permitted [Hepatitis B Surface Antigen (HBsAg) negative, anti-HBsAg positive and anti Hepatitis B core antigen (HBc) positive.]

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: Non randomisé
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Cohort
Dose escalation to maximum tolerated dose of GSK1120212 and Gemcitabine.
Continuous daily oral dosing while on study or disease progression (cycle = 28 days).
Dosing once weekly for 3 weeks in a 28 day cycle until disease progression.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Adverse events (AEs) and changes in laboratory values and vital signs.
Délai: From date of randomization until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.
From date of randomization until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.

Mesures de résultats secondaires

Mesure des résultats
Délai
Tumor response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v 1.1
Délai: At screening and every 8 weeks until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.
At screening and every 8 weeks until withdrawal from the study due to disease progression, AE, withdrawal of consent or study closure approximately 6 months after last subject was randomized.
drug levels in blood
Délai: first 15 days on study
first 15 days on study

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.

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)

12 août 2009

Achèvement primaire (Réel)

18 juillet 2011

Achèvement de l'étude (Réel)

18 juillet 2011

Dates d'inscription aux études

Première soumission

10 décembre 2009

Première soumission répondant aux critères de contrôle qualité

1 septembre 2011

Première publication (Estimation)

5 septembre 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

13 novembre 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

8 novembre 2017

Dernière vérification

1 novembre 2017

Plus d'information

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 GSK1120212

3
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