CP-751,871 Treatment For Patients With Multiple Myeloma

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: CP-751,871

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Pfizer Investigational Site
    • Scottsdale, Arizona, United States, 85259
      • Pfizer Investigational Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Pfizer Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10011-5903
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single agent CP-751,871; dose escalation design	Drug: CP-751,871; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (ACTUAL): June 1, 2008
• Study Completion (ACTUAL): June 1, 2008

Study Registration Dates

• First Submitted: February 14, 2012
• First Submitted That Met QC Criteria: February 15, 2012
• First Posted (ESTIMATE): February 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 15, 2013
• Last Update Submitted That Met QC Criteria: March 12, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: multiple myeloma; IGF-1R inhibitor; CP-751871
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: A4021001