This is a multicenter, worldwide, open-label study of MK-8353 in combination with selumetinib in participants with histologically or cytologically confirmed diagnosis of advanced solid tumor. This study will evaluate the safety, tolerability, and exploratory efficacy of MK-8353 in combination with selumetinib.
As specified by Phase 1 protocol-flexible language, modifications to the dose or dosing regimen can be made to achieve the scientific goals of the trial objectives and/or ensure appropriate safety of the trial participants. The proposed doses may be adjusted based on evaluation of safety, tolerability, and pharmacokinetic data.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Participants will receive MK-8353 orally twice daily (BID), escalated sequentially from 50 mg to 250 mg.
Participants will receive selumetinib orally BID, escalated sequentially from 25 mg to 75 mg.
Florida Cancer Specialists ( Site 7000)
Sarasota, Florida, United States
Next Oncology ( Site 0001)
San Antonio, Texas, United States
BC Cancer-Vancouver Center ( Site 0011)
Vancouver, British Columbia, Canada
Princess Margaret Cancer Centre ( Site 0012)
Toronto, Ontario, Canada
Number of Participants Experiencing Dose Limiting Toxicities
A dose limiting toxicity (DLT) is defined as any hematologic or non-hematologic toxicity ≥Grade 3 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The occurrence of any of the designated toxicities during Cycle 1 (3-week cycle) were considered a DLT, if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration. The number of participants experiencing DLTs was assessed.
Time frame: Cycle 1 (3-week Cycle) (Up to 3 weeks)
Number of Participants Experiencing Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants experiencing AEs was assessed.
Time frame: ~90 days after last treatment dose (up to ~45 weeks)
Number of Participants Discontinuing Study Treatment Due to AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants discontinuing study treatment due to AEs was assessed.
Time frame: Up to ~33 weeks
Area Under the Plasma Concentration-Time Curve for MK-8353 From Time 0 to 12 Hours
Blood samples were collected to determine the area under the curve from time 0 to 12 hours (AUC0-12). AUC is a measure of the amount of drug in the blood over time.
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Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 0020)
Bellinzona, Canton Ticino, Switzerland
Time frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
AUC0-12 for Selumetinib
Blood samples were collected to determine the AUC0-12. AUC is a measure of the amount of drug in the blood over time.
Time frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
Minimum Observed Plasma Concentration for MK-8353
Blood samples were collected to determine the minimum observed plasma concentration (Cmin) which is the minimum amount of drug in the plasma after the dose is given. In cases where Cmin values were below the limit of quantification (BLOQ), arithmetic mean (percent coefficient of variation \[%CV\]) was reported instead of geometric mean (percent geometric coefficient of variation \[%GCV\]), since geometric mean (%GCV) was not calculable. In cases where all Cmin values were BLOQ, mean was not calculable and indicated as "NA."
Time frame: Study Days 1 and 4 of Cycles 1 and 2 (3-week cycles). For Cycle 1, pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose; and for Cycle 2 pre-dose, and at 1 and 4 hours post-dose
Cmin for Selumetinib
Blood samples were collected to determine the Cmin which is the minimum amount of drug in the plasma after the dose is given. In cases where Cmin values were BLOQ, arithmetic mean (%CV) was reported instead of geometric mean (%GCV), since geometric mean (%GCV) was not calculable. In cases where all Cmin values were BLOQ, mean was not calculable and indicated as "NA."
Time frame: Study Days 1 and 4 of Cycles 1 and 2 (3-week cycles). For Cycle 1, pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose; and for Cycle 2 pre-dose, and at 1 and 4 hours post-dose
Maximum Observed Plasma Concentration for MK-8353
Blood samples were collected to determine the maximum observed plasma concentration (Cmax) which is the measure of the maximum amount of drug in the plasma after the dose is given.
Time frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose
Cmax for Selumetinib
Blood samples were collected to determine the Cmax which is the measure of the maximum amount of drug in the plasma after the dose is given.
Time frame: Study Days 1 and 4 of Cycle 1 (3-week cycle) at pre-dose and at 1, 2, 4, 6 hours, and between 8 and 12 hours post-dose