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Combination Study Of CP-751,871 With Paclitaxel And Carboplatin In Advanced Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00147537
First received: September 2, 2005
Last updated: October 1, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: CP-751,871
Drug: paclitaxel
Drug: carboplatin
Drug: erlotinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 282
Study Start Date: February 2005
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 2 (Arms A & B)
CP-751,871 + paclitaxel + carboplatin
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

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
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)

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of advanced/metastatic lung cancer

Exclusion Criteria:

  • Previous treatment with chemotherapy
  • Uncontrolled diabetes
  • History/active cardiovascular disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00147537

  Show 31 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00147537     History of Changes
Other Study ID Numbers: A4021002
Study First Received: September 2, 2005
Results First Received: January 18, 2013
Last Updated: October 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
non-small cell lung cancer
chemotherapy
figitumumab
insulin-like growth 1 factor receptor
IGF-IR
monoclonal antibody

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Erlotinib
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014