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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1, Open Label, Sequential Cohort, Dose Escalation Study Of CP-751,871 In Combination With Sunitinib In Patients With Advanced Solid Tumors

Conditions
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Advanced Cancer, Advanced Solid Tumors

Intervention / Treatment
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* Drug: CP-751,871
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 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: CP-751,871 + Sunitinib<br>Escalating cohorts of CP-751,871 + Sunitinib | Drug: CP-751,871<br>* CP-751,871 IV, every 3 weeks<br>Drug: Sunitinib<br>* Sunitinib - daily dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose-Limiting Toxicities (DLT) | 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. | Baseline up to the end of Cycle 1 (each cycle=3 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events Grade Version 3.0 | 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). | 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 Test Abnormality | 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). | 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 Test Abnormality | 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). | Baseline, Day 1 of every cycle, Days 8 and 15 of Cycle 1, up to end of treatment (28 days post last dose) | 
| 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 | AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration. | 0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, 15, and 22 of Cycles 1 and 4 | 
| Area Under the Curve From Time Zero to Day 22 [AUC504] of Figitumumab | 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. | 0.5 hour predose and 504 hours (Day 22) post-infusion of Cycles 1 and 4 | 
| Plasma Decay Half-Life (t1/2) of Figitumumab | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0.5 hour predose and 1 hour post-infusion on Days 1, 2, 4, 8, and 15 of Cycles 1 and 4 | 
| 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 | AUC24 is the area under the plasma concentration versus time curve from time zero (predose) to 24 hours postdose (0 to 24). | 0.5 hour predose and 2, 4, 6, 8, 12, and 24 hours postdose on Day 15 of Cycle 1 | 
| 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) | Assays for ADA assessment specific for figitumumab would have provided information regarding an immune response to the compound. | 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) | 
| Number of Participants With Objective Response (OR) | 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. | Baseline, Day 15 of every 2 cycles until disease progression up to follow-up (approximately 28 days following the last dose of study drug) |