A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)
3 novembre 2017 mis à jour par: Merck Sharp & Dohme LLC
A Phase I Study of Oral MK-2206 in Combination With Oral AZD6244 in Patients With Locally Advanced or Metastatic Solid Tumors
This study will investigate the safety and tolerability of combination therapy with MK-2206 and AZD6244 (selumetinib) and determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) for this drug combination in the treatment of participants with locally advanced or metastatic solid tumors. Preliminary efficacy data will also be collected.
The primary hypotheses for this study are that: 1) the Dose-limiting Toxicities (DLTs) observed in participants with locally advanced or metastatic solid tumors after administration of combination therapy with MK-2206 and AZD6244 will be dose-dependent and allow for identification of the MTD, and 2) oral administration of combination therapy with MK-2206 and AZD6244 to participants with advanced solid tumors will be generally well-tolerated.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
63
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:
- Participant has confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or therapies known to provide clinical benefit, or for whom efficacious standard therapy or any other therapy known to provide clinical benefit does not exist
- Participant has no history of prior cancer, except certain cervical, skin, or prostate cancers, or has undergone potentially curative therapy with no evidence of disease for 5 years
- At least 18 years of age
- Participant is able to swallow oral medications
- For participants enrolled in the MTD expansion cohorts, must have a diagnosis of Kirsten rat sarcoma viral oncogene homolog (KRAS) tumor-type non small-cell lung cancer (NSCLC). Additional tumor types (with specific mutations) may be added to the MTD expansion cohorts after discussion between Sponsor and Investigator
Exclusion Criteria:
- Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks of entering the study
- Participant is currently participating in or has participated in a study of an investigational compound or device within 30 days or 5x the compound's half-life of Cycle 1, Day 1
- Participant has known central nervous system metastases and/or carcinomatous meningitis
- Participant has a primary central nervous system tumor or spinal cord compression
- Participant is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse
- Participant is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study
- Participant is human immunodeficiency virus (HIV) positive
- Participant is has history of hepatitis B or C or active hepatitis A
- Participant has a history or current evidence of heart disease
- Participant has uncontrolled high blood pressure
- Participant has poorly controlled diabetes
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: MK-2206 45 mg QOD + AZD6244 75 mg QD
Participants receive MK-2206 45 mg oral tablets once every other day (QOD) PLUS AZD6244 75 mg oral capsules once daily (QD) starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 45 mg QOD + AZD6244 75 mg BID
Participants receive MK-2206 45 mg oral tablets QOD PLUS AZD6244 75 mg oral capsules twice daily (BID) starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 90 mg QW + AZD6244 50 mg BID
Participants receive MK-2206 90 mg oral tablets once weekly (QW) PLUS AZD6244 50 mg oral capsules BID starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 90 mg QW + AZD6244 75 mg QD
Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 75 mg oral capsules QD starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 90 mg QW + AZD6244 75 mg BID
Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 75 mg oral capsules BID starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 90 mg QW + AZD6244 100 mg QD
Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 90 mg QW + AZD6244 150 mg QD
Participants receive MK-2206 90 mg oral tablets QW PLUS AZD6244 150 mg oral capsules QD starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 100 mg QW + AZD6244 100 mg QD
Participants receive MK-2206 100 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
|
Expérimental: MK-2206 135 mg QW + AZD6244 100 mg QD
Participants receive MK-2206 135 mg oral tablets QW PLUS AZD6244 100 mg oral capsules QD starting on Day 1 of each 28-day cycle.
|
Oral tablets
Oral capsules
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of Participants With a Dose-limiting Toxicity (DLT)
Délai: Cycle 1 (Up to 28 days)
|
Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
DLTs included: Grade 4 neutropenia lasting for ≥7 days; Grade 3 or Grade 4 neutropenia with fever >38.5ºC and/or infection requiring antibiotic or anti-fungal treatment; Grade 4 thrombocytopenia (≤25.0 x 10^9/L); Grade ≥3 non-hematologic toxicity with exceptions; Any drug-related AE, regardless of CTCAE Grade, leading to a dose modification of MK-2206 or AZD6244; Unresolved CTCAE Grade ≥3 drug-related toxicity requiring drug interruption for >14 days; ≥ Grade 3 signs or symptoms of glucose intolerance and accompanied by ≥ Grade 2 hyperglycemia (glucose >160 dL or 8.9 mmol/L); ≥ Grade 3 electrolyte abnormalities due to glucose intolerance and not attributable to another cause; Diagnosis of lactoacidosis or ketoacidosis; Persistent increases in corrected QT (QTc) interval (>60 msec from baseline and/or >500 msec); Clinically significant bradycardia.
|
Cycle 1 (Up to 28 days)
|
|
Number of Participants Who Experienced at Least One Adverse Event (AE)
Délai: Up to approximately 23 months
|
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product.
Any worsening of a pre-existing condition which was temporally associated with the use of study drug was also an AE.
The number of participants who experienced at least one AE is presented.
|
Up to approximately 23 months
|
|
Number of Participants Who Discontinued Study Treatment Due to an AE
Délai: Up to approximately 20 months
|
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product.
Any worsening of a pre-existing condition which was temporally associated with the use of study drug was also an AE.
The number of participants who discontinued study treatment due to an AE is presented.
|
Up to approximately 20 months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of Participants With a Tumor Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Délai: Baseline and after every 8 weeks of treatment until documentation of objective response or disease progression (Up to 2 years)
|
Radiological evaluation (via computed tomography [CT] or magnetic resonance imaging [MRI]) of tumor response was assessed every 8 weeks post-treatment during Cycles 1-6, and per institutional standard of care in Cycle 7 and beyond.
The best overall tumor response was the best response based on RECIST 1.1 recorded from the start of the study treatment until the end of treatment.
Response categories included: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Participants whose tumor was not evaluable (NE) were missing a valid RECIST1.1 measurement at baseline.
The best overall tumor response for participants is presented.
|
Baseline and after every 8 weeks of treatment until documentation of objective response or disease progression (Up to 2 years)
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
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)
23 novembre 2009
Achèvement primaire (Réel)
26 novembre 2012
Achèvement de l'étude (Réel)
16 juillet 2014
Dates d'inscription aux études
Première soumission
25 novembre 2009
Première soumission répondant aux critères de contrôle qualité
25 novembre 2009
Première publication (Estimation)
30 novembre 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
7 août 2018
Dernière mise à jour soumise répondant aux critères de contrôle qualité
3 novembre 2017
Dernière vérification
1 novembre 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 2206-010
- 2009_698 (Autre identifiant: Merck Registration Number)
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
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 .