CP-751,871 Treatment For Patients With Multiple Myeloma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma	Drug: CP-751,871	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open Label Phase I Study Of CP-751,871 In Patients With Multiple Myeloma

Resource links provided by NLM:

MedlinePlus related topics: Multiple Myeloma

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) [ Time Frame: Baseline up to Cycle 1 (Week 4 or Week 8) ] [ Designated as safety issue: Yes ]
The highest dose level at which not more than 1 dose-limiting toxicity (DLT) was observed during Cycle 1 in 6 participants

Secondary Outcome Measures:

Single Dose End-of-infusion Concentration (Cinf) for CP-751,871 [ Time Frame: 1 hour postdose in Cycle 1 ] [ Designated as safety issue: No ]
Single Dose Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for CP-751,871 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Single Dose Volume of Distribution (Vz) for CP-751,871 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Single Dose Plasma Decay Half-life (t1/2) for CP-751,871 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Single Dose Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for CP-751,871 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Single Dose Volume of Distribution at Steady State (Vss) for CP-751,871 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Single Dose Systemic Clearance (CL) for CP-751,871 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Multiple Dose Cinf for CP-751,871 [ Time Frame: 1 hour postdose in Cycles 2 up to 16 ] [ Designated as safety issue: No ]
Multiple Dose Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871 [ Time Frame: 0 hour (predose) in Cycles 2 up to 16 ] [ Designated as safety issue: No ]
Pharmacodynamic-based Dose [ Time Frame: Cycle 1 (Week 4 or Week 8) ] [ Designated as safety issue: No ]
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
Human Anti-human Antibody (HAHA) Response to CP-751,871 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline, Day 1 at predose/cycle, end of study (30-60 days post last dose) ] [ Designated as safety issue: No ]
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).
Time to Disease Progression [ Time Frame: Baseline up to end of treatment ] [ Designated as safety issue: No ]
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])

Enrollment:	47
Study Start Date:	December 2003
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01536145

Locations

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

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01536145 History of Changes
Other Study ID Numbers:	A4021001
Study First Received:	February 14, 2012
Results First Received:	January 18, 2013
Last Updated:	March 12, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

IGF-1R inhibitor
CP-751871
multiple myeloma

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 16, 2013