Investigate safety, tolerability and pharmacokinetics of CP-751,871 when given in combination with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Chemotherapy (carboplatin and paclitaxel) and CP-751,871 (6, 10 or 20mg/kg) will be administered by intravenous infusion every three weeks.
Pfizer Investigational Site
Chuo-ku, Tokyo, Japan
Number of Participants With Dose Limiting Toxicities (DLT)
A DLT was defined as any one of the following adverse events observed in Cycle 1 which was considered as related to CP-751,871 combination therapy; 1) \>=Grade 3 gastrointestinal toxicity, hyperglycemia and/or fatigue despite the use of adequate/optimal medical intervention, 2) Any other \>=Grade 3 toxicity not classified under CTCAE blood/bone marrow, or 3) Grade 4 neutropenia that persisted for \>=7 consecutive days or was complicated by fever (defined as a body temperature \>38.0 Celsius degree), 4) Grade 3 thrombocytopenia which needed blood transfusion or Grade 4 thrombocytopenia.
Time frame: Cycle 1
Maximum Observed Concentration (Cmax) of CP-751,871
Time frame: Cycles 1 and 4 at prior to dosing of CP-751,871 (Day 1), and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Cycle 1 : prior to CP-751,871 (Day 1) dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
Area Under the Plasma Concentration-time Curve From Time 0 to Day 22 (AUC0-day22)
AUC(0-day22) : AUC from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sampling for the next cycle. AUC(0-day22) was calculated using the linear/log trapezoidal method.
Time frame: Cycle 1: prior CP-751,871 (Day 1) to dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
Area Under the Plasma Concentration Curve From Time Zero to Tau (AUCtau)
AUCtau: AUC from time zero to tau, the dosing interval, where tau is the actual time of the predose sampling for the next cycle. AUCtau was calculated using the linear/log trapezoidal method.
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Time frame: Cycle 4: prior to CP-751,871 (Day 1) dosing , and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
Observed Accumulation Ratio (Rac)
The ratio of Cycle 4 AUCtau to Cycle 1 AUCtau
Time frame: Cycle 1 and Cycle 4: prior to CP-751,871 (Day 1) dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion
Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1)
IGF-1 is one of the IGF-axis related biomarkers.
Time frame: Day 1 of Cycles 1 to 6, Day 8 of Cycles 1 to 4, and end of study
Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3)
IGF-BP3 is one of the IGF-axis related biomarkers.
Time frame: Day 1 of Cycles 1-6, Day 8 of Cycles 1-4, and end of treatment
Number of Participants With Positive Anti-Drug Antibody (ADA) Specific to CP-751,871 Following an Intravenous Infusion of CP-751,871.
The screening assay for anti-CP-751,871 antibodies was performed.
Time frame: Day 1 of Cycles 1 (predose) and 4, and end of study
Number of Participants With Objective Response
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Time frame: Baseline up to 6 cycles (1 cycle = 21 days)
Progression-Free Survival (PFS)
PFS is the period from the registration to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
Time frame: Baseline up to 6 cycles (1 cycle = 21 days)