This clinical study evaluates the safety, tolerability, pharmacokinetics, and immunogenicity of dalotuzumab (MK-0646) in participants with relapsed or refractory locally advanced or metastatic solid tumors using once weekly and once every other week dose infusion regimens. The primary study hypothesis is that administration of dalotuzumab as a once weekly and an every other week infusion will be generally safe and well tolerated
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
IV infusion
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. DLTs were defined as the occurrence of any of the following events when judged to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except alopecia and inadequately treated diarrhea, nausea and vomiting. The number of participants who experienced a DLT is presented.
Time frame: Cycle 1 (Up to 4 weeks)
Number of Participants Who Experienced an Adverse Event (AE)
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 the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Time frame: Up to 30 days after last dose of study treatment (Up to 101 days)
Number of Participants Who Discontinued Study Treatment Due to an AE
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 the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to 71 days
Maximum Plasma Concentration (Cmax) of Dalotuzumab
Cmax was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
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Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞) of Dalotuzumab
AUC0-∞ was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Time to Cmax (Tmax) of Dalotuzumab
Tmax was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Apparent Terminal Half-life (t1/2) of Dalotuzumab
t1/2 was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Clearance (CL) of Dalotuzumab
CL of dalotuzumab was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Steady State Volume of Distribution (Vss) of Dalotuzumab
Vss was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Number of Participants Who Developed a Human Anti-Humanized Antibody (HAHA) Response to Dalotuzumab
Formation of HAHAs may block efficacy by substantially increasing the clearance of dalotuzumab and limit the possibility of future dalotuzumab therapy. The occurrence of HAHAs in the sera of dalotuzumab treated participants at any of the serum collection times was assessed.
Time frame: Cycle 1: predose on Days 1, 8, 15, and 22; Cycles 2 and 3: predose on Day 1; 4 weeks after last dose of study drug