Study Of Anti-IGF-IR CP-751,871 In Patients With Solid Tumors

Study Overview
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Brief Summary
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This is a phase 1 study of anti-IGF-IR CP-751,871 in patients with solid tumors currently enrolling patients 9 years old and older with Ewing's sarcoma family of tumors (Ewing's, PNET and Askin's).

Official Title
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Phase 1, Open Label, Multiple Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of CP 751,871 In Patients With Advanced Solid Tumors

Conditions
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Sarcoma, Ewing's

Intervention / Treatment
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* Drug: CP-751,871


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Ewing's sarcoma family tumors Exclusion Criteria: Concurrent treatment with any other anti tumor agents

Ages Eligible for Study
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Minimum Age: 9 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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: 1<br> | Drug: CP-751,871<br>* Currently dosing at 20 mg/kg, IV on day 1 of each 28 day cycle until progression or unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 150 days after last dose that were absent before treatment or that worsened relative to pretreatment state. | Baseline up to 150 days after the last administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) in Cycle 1 |  | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Maximum Observed Plasma Concentration (Cmax) in Cycle 4 |  | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1 |  | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 4 |  | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Plasma Decay Half-Life (t1/2) in Cycle 1 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Plasma Decay Half-Life (t1/2) in Cycle 4 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1 |  | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 4 |  | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Systemic Clearance (CL) in Cycle 1 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Systemic Clearance (CL) in Cycle 4 | CL is a quantitative measure of the rate at which a drug substance is removed from the body. | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Concentration at End of Infusion (Cendinf) in Cycle 1 |  | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Concentration at End of Infusion (Cendinf) in Cycle 4 |  | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Volume of Distribution (Vz) in Cycle 1 | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Volume of Distribution (Vz) in Cycle 4 | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Volume of Distribution at Steady State (Vss) in Cycle 1 | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the Vz at steady-state. | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Volume of Distribution at Steady State (Vss) in Cycle 4 | Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the Vz at steady-state. | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1 | Area under the plasma concentration time-curve from zero to the last measured concentration | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 4 | Area under the plasma concentration time-curve from zero to the last measured concentration | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1 | Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1 |  | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 4 |  | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 1 |  | Cycle 1: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 4 |  | Cycle 4: 0 (predose), 1, 24 and 72 hours, 7 and 14 days postdose | 
| Human Anti-human Antibodies (HAHA) Levels | HAHA were indicators of immunogenicity to figitumumab. | 30 minutes predose in Cycles 1 up to 61, and last scheduled follow-up visit (up to 150 days from the last dose of study drug) | 
| Number of Circulating Tumor Cells (CTCs) | Quantification of CTCs using an automated microscope system | 30 minutes predose in all cycles (up to 17); 1, 3, 7, and 14 days postdose in Cycle 1 for dose escalation and RP2D extension cohorts; and also 1 day postdose in Cycle 4 for RP2D extension cohort | 
| Number of Insulin-like Growth Factor 1 Receptor (IGF-1R) Positive CTCs | Quantification of IGF-IR positive CTCs using an automated microscope system | 30 minutes predose in all cycles (up to 17); 1, 3, 7, and 14 days postdose in Cycle 1 for dose escalation and RP2D extension cohorts; and also 1 day postdose in Cycle 4 for RP2D extension cohort |