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Trial record 1 of 1 for:    NCT00147537
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Combination Study Of CP-751,871 With Paclitaxel And Carboplatin In Advanced Lung Cancer

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ClinicalTrials.gov Identifier: NCT00147537
Recruitment Status : Completed
First Posted : September 7, 2005
Results First Posted : April 24, 2013
Last Update Posted : October 30, 2013
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE September 2, 2005
First Posted Date  ICMJE September 7, 2005
Results First Submitted Date  ICMJE January 18, 2013
Results First Posted Date  ICMJE April 24, 2013
Last Update Posted Date October 30, 2013
Study Start Date  ICMJE February 2005
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2013)
  • Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b [ Time Frame: Start of treatment (baseline) up to the end of Cycle 1 (Day 21) ]
    The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity.
  • Recommended Phase 2 Dose (RP2D): Phase 1b [ Time Frame: Start of treatment (baseline) up to the end of Cycle 1 (Day 21) ]
  • Objective Response Rate: Phase 2 [ Time Frame: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization ]
    Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
  • Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2 [ Time Frame: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization ]
    Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Original Primary Outcome Measures  ICMJE
 (submitted: September 2, 2005)
Antitumor efficacy measured as Objective Responses using RECIST criteria. Determined at the end of study.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2013)
  • Objective Response Rate: Phase 1b [ Time Frame: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization ]
    Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
  • Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b [ Time Frame: Day 1 pre-infusion of each cycle up to Cycle 17 (each cycle was 21 day), 150 days after the last CP-751,871 infusion, and last follow up visit (one year post last study dose) ]
    HAHA are indicators of immunogenicity to CP-751,871.
  • Number of Circulating Endothelial Cells (CECs): Phase 1b [ Time Frame: Day 1 pre-dose and Days 15 to 21 of Cycle 4 ]
  • Number of Circulating Tumor-Related Cells (CTCs) and CTC Insulin-Like Growth Factor 1 Receptor (IGF-IR) Expression: Phase 1b [ Time Frame: Day 1 pre-dose and Days 15 to 21 of Cycle 4 ]
    Blood samples were collected to enumerate the number of total CTCs and CTC insulin-like growth factor 1 receptor (IGF-IR) expression
  • Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b [ Time Frame: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) ]
  • Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) ]
  • Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 1 in Phase 1b [ Time Frame: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) ]
    AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504)
  • Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 1b [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) ]
    AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504)
  • Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b [ Time Frame: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) ]
    AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time.
  • Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b [ Time Frame: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b [ Time Frame: Cycle 2 pre-infusion (which is the end of Cycle 1) ]
    Concentration at 504 hours post dose
  • CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b [ Time Frame: Cycle 5 pre-infusion (which is the end of Cycle 4) ]
    Concentration at 504 hours post dose
  • Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b [ Time Frame: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1). Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). ]
    Accumulation ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac)
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b [ Time Frame: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
  • Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b [ Time Frame: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) ]
    Maximum Observed Plasma Concentration
  • Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is then end of Cycle 4) ]
    Maximum Observed Plasma Concentration
  • Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2 [ Time Frame: Day 1 pre-infusion of each Cycle (each cycle was 21 day) up to Cycle 17 and 150 days after the last CP-751,871 infusion ]
    HAHA are indicators of immunogenicity to CP-751,871
  • M.D. Anderson Symptom Assessment Inventory (MDASI) in Phase 2 [ Time Frame: Day 1 pre-dose of Cycle 1, weekly for Cycle 1 and 2, monthly prior to each subsequent cycle (Cycle 3 up to Cycle 17, each cycle was 21 day), and follow up (one year post last study dose) ]
    The MDASI is a 19-item questionnaire that assesses the severity of 13 symptoms over the past 24 hours, as well as how much the symptoms interfered with 6 areas of function (eg, walking, work, mood), when the symptom was "at its worst". Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was "as bad as you can imagine" or "interfered completely" with their life. Total average score range: 0 to 10.
  • The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC-QLQ-C30/-LC13) in Phase 2 [ Time Frame: Day 1 pre-dose of Cycle 1, monthly prior to each cycle (up to 17 cycles, each cycle was 21 day), and follow up (one year post last study dose) ]
    The QLQ-C30/-LC13 is a 43 item, self-administered questionnaire designed to assess health outcomes in clinical trials. In addition to global quality of life, the measure assesses 5 functional domains (physical, role, cognitive, emotional and social functioning) and specific symptoms (eg, nausea, pain). Each item is rated on a 1-4 scale with '1' representing "not at all" and '4' "very much". Within domains, items are scored to obtain a total score with higher scores representative of poorer HRQoL. Scale score range: 0 to 100.
  • Apparent Volume of CP-751,871 Distribution (Vd) for Cycle 4 in Phase 2 [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
  • Clearance (CL) of CP-751,871 for Cycle 4 in Phase 2 [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). ]
    Systemic clearance.
  • Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 2 [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). ]
    AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504)
  • CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 2 [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). ]
    Concentration at 504 hours post dose
  • Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 2 [ Time Frame: Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). ]
    Maximum Observed Plasma Concentration
  • Progression-Free Survival (PFS): Phase 2 [ Time Frame: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization ]
    Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]).
  • Time to Progression (TTP) in Phase 2 [ Time Frame: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization ]
    Time in months from start of study treatment to first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]).
  • Duration of Response (DR) in Phase 2 [ Time Frame: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization ]
    Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2005)
Safety,pharmacokinetics,pharmacodynamics of CP-751,871/paclitaxel/ carboplatin
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Study Of CP-751,871 With Paclitaxel And Carboplatin In Advanced Lung Cancer
Official Title  ICMJE A Phase 1b Dose Escalation/Phase 2 Randomized, Non-Comparative, Multiple Center, Open Label Study Of CP 751,871 In Combination With Paclitaxel And Carboplatin And Of Paclitaxel And Carboplatin Alone As First Line Treatment For Advanced Non-Small Cell Lung Cancer
Brief Summary

Phase 1b Dose Excalation/Expansion: Identify and characterize safety and tolerability of recommended phase 2 dose of CP-751,871 when administered with paclitaxel and carboplatin Phase 1b Erlotinib Extension: To characterize the safety and tolerability of CP751,871 when administered with paclitaxel, carboplatin and erlotinib.

Phase 2: To test the efficacy of CP-751,871 combined with paclitaxel and carboplatin in the treatment of advanced non-small cell lung cancer

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: CP-751,871

    Phase 2 Arm A:

    CP-751,871 20 mg/kg IV over 2.5 hours up to 17 cycles

  • Drug: paclitaxel

    Phase 2 Arm A:

    Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles

    Phase 2 Arm B:

    Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles

  • Drug: carboplatin

    Phase 2 Arm A:

    Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles

    Phase 2 Arm B:

    Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles

  • Drug: CP-751,871
    Phase 1b Dose Escalation/Expansion: CP-751,871 20 mg/kg IV over 2.5 hours (up to 17 cycles) Phase 1b Erlotinib Extension: CP-751,871 20 mg/kg IV over 2.5 hours (up to 17 cycles)
  • Drug: paclitaxel
    Phase 1b Dose Escalation/Expansion: paclitaxel 200 mg/m2, IV over 3 hours (up to 6 cycles) Phase 1b Erlotinib Extension: paclitaxel 200 mg/m2, IV over 3 hours (up to 6 cycles)
  • Drug: carboplatin
    Phase 1b Dose Escalation/Expansion: carboplatin AUC 6, IV over 15-60 minutes (up to 6 cycles) Phase 1b Erlotinib Extension: carboplatin AUC 6, IV over 15-60 minutes (up to 6 cycles)
  • Drug: erlotinib
    Phase 1b Erlotinib Extension: erlotinib 150 mg/day orally every day (up to 17 cycles)
Study Arms  ICMJE
  • Experimental: Phase 2 (Arms A & B)
    CP-751,871 + paclitaxel + carboplatin
    Interventions:
    • Drug: CP-751,871
    • Drug: paclitaxel
    • Drug: carboplatin
  • Experimental: Phase 1b
    1. Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin
    2. Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib
    Interventions:
    • Drug: CP-751,871
    • Drug: paclitaxel
    • Drug: carboplatin
    • Drug: erlotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 15, 2011)
282
Original Enrollment  ICMJE
 (submitted: September 2, 2005)
180
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of advanced/metastatic lung cancer

Exclusion Criteria:

  • Previous treatment with chemotherapy
  • Uncontrolled diabetes
  • History/active cardiovascular disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00147537
Other Study ID Numbers  ICMJE A4021002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP