Conditions: Cancer
Keywords: Oncology, GSK1120212, MEK inhibitor, hematological malignancies, AML CMML MDS
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 97
Healthy volunteers: no

Brief summary:
MEK111759 is a dose-escalation, Phase I/II, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 in subjects with relapsed or refractory leukemias. The recommended dose and regimen will be selected based on the safety, pharmacokinetic, and pharmacodynamic profiles. This study will identify the maximum tolerated and recommended Phase II doses using a dose-escalation procedure. Dose escalations will continue based on predefined parameters until a maximum tolerated dose is established. In Phase II, the clinical efficacy of GSK1120212 in subjects with relapsed or refractory leukaemias (AML, MDS or CMML) will be determined.

Detailed description:

Arms:
arm 1: The proposed treatment schedule of GSK1120212 is continuous daily dosing. At the initiation of dosing, a loading dose will be given prior to starting continuous dosing (maintenance dose).

Alterations to the dose and schedule will be based on emerging PK, PD, and tolerability data. The goal will be to define a regimen that is well tolerated and provides adequate PK and PD. This will be the recommended Phase II schedule. arm 2: A dose determined by Phase I to further evaulate the safety profile, PK, PD, and clinical activity of GSK1120212.

Interventions: intervention 1: GSK1120212 intervention 2: GSK1120212
Intervention descriptions: intervention 1: Starting dose based on GSK protocol MEK111054 and then dose escalation based on Dose Limiting Toxicities per protocol. intervention 2: Dose will be maximum tolerated dose based on Phase I results.

Protocol document: