Study Of CP-751,871 In Combination With Sunitinib In Patients With Advanced Solid Tumors

Phase 1

Terminated

Conditions: Advanced Cancer
Advanced Solid Tumors

Interventions: Drug: CP-751,871
Drug: Sunitinib

Registration Number: NCT00729833

Lead Sponsor: Pfizer

Brief Summary: The study is being conducted to determine the maximum tolerated dose, overall safety and tolerability profile, and pharmacokinetic profile of CP-751,871 and sunitinib when given in combination with advanced solid tumors.

Detailed Description: The study was closed to enrollment on 14 Jan 2011 and terminated secondary to excessive screen failure rate and for business reasons associated with Pfizer's business decision to stop development of the figitumumab compound. Safety concerns did not contribute to the decision to terminate this clinical trial.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 45

Inclusion Criteria

Histologically or cytologically confirmed advanced solid tumors relapsed or refractory to standard therapy or for whom no standard therapy exists.
ECOG Performance Status of 0 or 1;
Total IGF-1 level ≥100 ng/ml;
ECOG Performance Status of 0 or 1
Adequate bone marrow, renal, and hepatic function

Exclusion Criteria

Concurrent treatment with any antitumor agents with the exception of LHRH agnosits for prostate cancer patients
Treatment with any other investigational therapy within 4 weeks prior to study treatment
Major surgery within 4 weeks of study treatment
Prior treatment that may increase the risk of cardiac complications
Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2 or greater
Significant active cardiac disease, including hypertension that cannot be controlled by medications
Greater than three (3) prior lines of cytotoxic therapy;
Active infection
Prior IGF-IR targeted therapy;

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CP-751,871 + Sunitinib	CP-751,871	Escalating cohorts of CP-751,871 + Sunitinib
CP-751,871 + Sunitinib	Sunitinib	Escalating cohorts of CP-751,871 + Sunitinib

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose-Limiting Toxicities (DLT)	Baseline up to the end of Cycle 1 (each cycle=3 weeks)	Number of participants with treatment-related Grade 3/4 toxicities that occurred during the defined time frame or that resulted in greater than or equal to (\>=) 7 days delay in administration of Cycle 2. Toxicities were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events Grade Version 3.0	Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than one occurrence in the same preferred term event category, only the worst CTCAE grade was reported. Severity grades were 0 (no change from normal or reference range), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), and 5 (death).
Percentage of Participants With Hematologic Laboratory Test Abnormality	Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose)	Percentage of participants with hematologic laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling).
Percentage of Participants With Blood Chemistry Laboratory Test Abnormality	Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose)	Percentage of participants with blood chemistry laboratory abnormalities of CTC severity grades 1, 2, 3, or 4 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening or disabling).
Plasma Concentration at the End of Infusion (Cendinf) of Figitumumab	0.5 hour predose and 1 hour post-infusion on Day 1 of Cycles 1 and 4
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab	0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, 15, and 22 of Cycles 1 and 4	AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration.
Area Under the Curve From Time Zero to Day 22 [AUC504] of Figitumumab	0.5 hour predose and 504 hours (Day 22) post-infusion of Cycles 1 and 4	AUC504 is the area under the plasma concentration versus time curve from time zero (predose) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle.
Plasma Decay Half-Life (t1/2) of Figitumumab	0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, and 15 of Cycles 1 and 4	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Maximum Observed Plasma Concentration (Cmax) of Sunitinib	0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sunitinib	0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1
Area Under the Curve From Time Zero to 24 Hours Postdose (AUC24) of Sunitinib	0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1	AUC24 is the area under the plasma concentration versus time curve from time zero (predose) to 24 hours postdose (0 to 24).
Trough Plasma Concentration (Ctrough) of Sunitinib	0.5 hour predose on Day 1 of Cycle 2
Plasma Concentration at 24 Hours Postdose (C24) of Sunitinib	24 hours postdose on Day 15 of Cycle 1
Number of Participants With Anti-Drug Antibodies (ADA)	0.5 hour pre-infusion on Day 1 in Cycles 1 and 2, at end of treatment, and during the last scheduled follow-up visit (5 months from the last dose of study drug)	Assays for ADA assessment specific for figitumumab would have provided information regarding an immune response to the compound.
Number of Participants With Objective Response (OR)	Baseline, Day 15 of every 2 cycles until disease progression up to follow-up (approximately 28 days following the last dose of study drug)	Objective response (OR) was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. CR was the complete disappearance of all target and non-target disease, no new lesions, or the normalization of markers (if markers were being followed). PR was greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions, no unequivocal progression of non-target disease, no new lesions, or no reappearance of lesions after a CR. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.