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

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

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).

Study Overview

• Status: Completed
• Conditions: Sarcoma, Ewing's
• Intervention / Treatment: Drug: CP-751,871

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Pfizer Investigational Site
• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0848
      • Pfizer Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Ewing's sarcoma family tumors

Exclusion Criteria:

• Concurrent treatment with any other anti tumor agents

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: CP-751,871; Currently dosing at 20 mg/kg, IV on day 1 of each 28 day cycle until progression or unacceptable toxicity

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Asmane I, Watkin E, Alberti L, Duc A, Marec-Berard P, Ray-Coquard I, Cassier P, Decouvelaere AV, Ranchere D, Kurtz JE, Bergerat JP, Blay JY. Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas. Eur J Cancer. 2012 Nov;48(16):3027-35. doi: 10.1016/j.ejca.2012.05.009. Epub 2012 Jun 7.
• Olmos D, Postel-Vinay S, Molife LR, Okuno SH, Schuetze SM, Paccagnella ML, Batzel GN, Yin D, Pritchard-Jones K, Judson I, Worden FP, Gualberto A, Scurr M, de Bono JS, Haluska P. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study. Lancet Oncol. 2010 Feb;11(2):129-35. doi: 10.1016/S1470-2045(09)70354-7. Epub 2009 Dec 23.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: May 16, 2007
• First Submitted That Met QC Criteria: May 16, 2007
• First Posted (Estimate): May 17, 2007

Study Record Updates

• Last Update Posted (Estimate): December 17, 2013
• Last Update Submitted That Met QC Criteria: October 25, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Neuroectodermal Tumors, Primitive; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral
• Other Study ID Numbers: A4021010