Study of CP-751,871 in Combination With Carboplatin and Paclitaxel in Advanced Lung Cancer

Study Overview
=================
Brief Summary
-----------------
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

Official Title
-----------------
Phase 1, Dose Escalation Study of CP-751,871 in Combination With Carboplatin and Paclitaxel in Previously Untreated Patients With Advanced Non-Small Cell Lung Cancer

Conditions
-----------------
Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
-----------------
* Drug: CP-751,871 + carboplatin + paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of advanced non-small cell lung cancer Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Any prior treatment for non-small cell lung cancer Brain metastases With diabetes

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CP-751,871<br> | Drug: CP-751,871 + carboplatin + paclitaxel<br>* Chemotherapy (carboplatin and paclitaxel) and CP-751,871 (6, 10 or 20mg/kg) will be administered by intravenous infusion every three weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Cycle 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of CP-751,871 |  | 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. | 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. | 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. | 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 | 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. | 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. | 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. | 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. | 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. | Baseline up to 6 cycles (1 cycle = 21 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CP-751,871, Non-small cell lung cancer, Phase 1