CP-751,871 Treatment For Patients With Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT01536145
• Recruitment Status: Completed
• First Posted: February 20, 2012
• Results First Posted: February 28, 2013
• Last Update Posted: March 15, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: February 14, 2012
• First Posted Date: February 20, 2012
• Results First Submitted Date: January 18, 2013
• Results First Posted Date: February 28, 2013
• Last Update Posted Date: March 15, 2013
• Study Start Date: December 2003
• Actual Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2013)

Maximum Tolerated Dose (MTD) [ Time Frame: Baseline up to Cycle 1 (Week 4 or Week 8) ]

The highest dose level at which not more than 1 dose-limiting toxicity (DLT) was observed during Cycle 1 in 6 participants

Original Primary Outcome Measures (submitted: February 15, 2012)

• Maximum tolerated dose (MTD) [patients treated at doses ≤ 0.15 mg/kg] [ Time Frame: 4 weeks ]
• Maximum tolerated dose (MTD) [patients treated at doses > 0.15 mg/kg] [ Time Frame: 8 weeks ]

Current Secondary Outcome Measures (submitted: January 18, 2013)

• Single Dose End-of-infusion Concentration (Cinf) for CP-751,871 [ Time Frame: 1 hour postdose in Cycle 1 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• Multiple Dose Cinf for CP-751,871 [ Time Frame: 1 hour postdose in Cycles 2 up to 16 ]
• Multiple Dose Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871 [ Time Frame: 0 hour (predose) in Cycles 2 up to 16 ]
• Pharmacodynamic-based Dose [ Time Frame: Cycle 1 (Week 4 or Week 8) ]
  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 ]
• Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline, Day 1 at predose/cycle, end of study (30-60 days post last dose) ]
  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 ]
  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])

Original Secondary Outcome Measures (submitted: February 15, 2012)

• Single dose end of infusion concentration [Cinf] for CP-751,871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Single dose initial volume distribution [Vd] for CP-751,871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Single dose area under plasma disposition curve from 0 to last time point [AUC0-Tlast] with measurable CP-751, 871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Single dose terminal disposition phase half-life [t1/2] for CP-751, 871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Single dose area under the plasma disposition curve from 0 to infinity [AUC0-inf] for CP-751, 871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Single dose clearance rate [CL] for CP-751,871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Single dose steady-state volume [Vss] for CP-751,871 [ Time Frame: Cycle 1:Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Single dose area under the plasma moment curved from 0 to infinity [AUMC0-inf] for CP-751,871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Multiple dose end infusion concentration [Cinf] for CP-751,871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Multiple dose concentration at the end of the dosing interval [Cmin] for CP-751,871 [ Time Frame: Cycle 1: Days 1, 2, 3, 4, 8, 15, 22 and 29; 30-60 days post last dose of CP-751,871 ]
• Pharmacodynamics: serum Insulin Growth Factor-1, IGF binding protein-3 and acid-labile subunit [ Time Frame: Cycle 1 pre-dose, 48,72 hrs post dose; day 43; subsequent cycles day 1 pre-dose ]
• Human Anti-Human Antibodies [HAHA] [ Time Frame: Cycle 1 Day 1 pre-dosing, day 1 of each cycle, and end of study [30-60 days post last dose] ]
• Response rate [ Time Frame: Baseline, Day 1 at pre-dosing/cycle, end of study [30-60 days post last dose] ]
• Time to disease progression [ Time Frame: Baseline, Day 1 at pre-dosing/cycle, end of study [30-60 days post last dose] ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CP-751,871 Treatment For Patients With Multiple Myeloma
• Official Title: An Open Label Phase I Study Of CP-751,871 In Patients With Multiple Myeloma
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

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

Study Arms

Experimental: Single agent CP-751,871

dose escalation design

Intervention: Drug: CP-751,871

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 16, 2012): 47
• Original Actual Enrollment (submitted: February 15, 2012): 50
• Actual Study Completion Date: June 2008
• Actual Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01536145
• Other Study ID Numbers: A4021001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2013