CP-751,871 Treatment For Patients With Multiple Myeloma

Study Overview
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Brief Summary
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This study represents the first-in-human study for CP-751,871. The study aimed to define the safety, tolerability, and maximum tolerated dose of CP-751,871 in patients with multiple myeloma through a dose escalation design.

Official Title
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An Open Label Phase I Study Of CP-751,871 In Patients With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: CP-751,871


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously treated multiple myeloma with a quantifiable serum (M spike ≥ 1 g/dL) and/or urine (≥ 200 mg/24-hr) paraprotein Adequate bone marrow, renal, liver and cardiac function Eastern Cooperative Oncology Group [ECOG] performance status less than or equal to 2 Exclusion Criteria: Prior allogeneic stem cell transplant (alloSCT) Myelosuppressive chemotherapy or immunotherapy within 3 weeks prior to treatment with CP-751,871 Prior organ allograft Concurrent use of insulin, oral hypoglycemic medication, growth hormone (GH), or growth hormone inhibitors Female patients who are pregnant or lactating

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single agent CP-751,871<br>dose escalation design | Drug: CP-751,871<br>* CP-751,871 was given at doses ranging from 0.025 mg/kg up to 20 mg/kg IV every 4 weeks until disease progression or lack of tolerability<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | The highest dose level at which not more than 1 dose-limiting toxicity (DLT) was observed during Cycle 1 in 6 participants | Baseline up to Cycle 1 (Week 4 or Week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose End-of-infusion Concentration (Cinf) for CP-751,871 |  | 1 hour postdose in Cycle 1 | 
| Single Dose Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CP-751,871 |  | Cycle 1: predose; 1; 24; 48; 72; 168; 336; 504, 672 and 1008 (for participants with an up to 8-week Cycle 1 only) hours postdose | 
| Single Dose Volume of Distribution (Vz) for CP-751,871 |  | Cycle 1: predose; 1; 24; 48; 72; 168; 336; 504 and 672 and 1008 (for participants with an up to 8-week Cycle 1 only) hours postdose | 
| Single Dose Plasma Decay Half-life (t1/2) for CP-751,871 |  | Cycle 1: predose; 1; 24; 48; 72; 168; 336; 504 and 672 and 1008 (for participants with an up to 8-week Cycle 1 only) hours postdose | 
| Single Dose Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for CP-751,871 |  | Cycle 1: predose; 1; 24; 48; 72; 168; 336; 504 and 672 and 1008 (for participants with an up to 8-week Cycle 1 only) hours postdose | 
| Single Dose Volume of Distribution at Steady State (Vss) for CP-751,871 |  | Cycle 1: predose; 1; 24; 48; 72; 168; 336; 504 and 672 and 1008 (for participants with an up to 8-week Cycle 1 only) hours postdose | 
| Single Dose Systemic Clearance (CL) for CP-751,871 |  | Cycle 1: predose; 1; 24; 48; 72; 168; 336; 504 and 672 and 1008 (for participants with an up to 8-week Cycle 1 only) hours postdose | 
| Multiple Dose Cinf for CP-751,871 |  | 1 hour postdose in Cycles 2 up to 16 | 
| Multiple Dose Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871 |  | 0 hour (predose) in Cycles 2 up to 16 | 
| Pharmacodynamic-based Dose | The dose associated with PK exposure that was associated with 80% of the maximal effect based on down-regulation of insulin-like growth factor 1 receptor (IGF-1R) expression | Cycle 1 (Week 4 or Week 8) | 
| Human Anti-human Antibody (HAHA) Response to CP-751,871 |  | 30 minutes predose in Cycle 1 and subsequent cycles, end of study visit (Days 30 and 60) for dose levels below 0.8 mg/kg; 30 minutes predose in Cycle 1 and last scheduled follow-up visit for dose levels greater than or equal to 0.8 mg/kg | 
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Southwest Oncology Group (SWOG) criteria. CR were those with absence of bone marrow or blood findings of multiple myeloma. PR were those with a 50-74% reduction in the quantitative immunoglobulin, and if present, a 50-89% reduction in the urine M-component (Bence-Jones protein). | Baseline, Day 1 at predose/cycle, end of study (30-60 days post last dose) | 
| Time to Disease Progression | Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever came first. Tumor progression was determined from oncologic assessment data (where data met the criteria for progressive disease [PD]) | Baseline up to end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IGF-1R inhibitor, CP-751871, multiple myeloma