Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Chemotherapy-Naïve Patients With Advanced Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00560573
First received: November 15, 2007
Last updated: March 15, 2013
Last verified: March 2013

November 15, 2007
March 15, 2013
November 2007
June 2008   (final data collection date for primary outcome measure)
Number of Participants With Dose-limiting Toxicities (DLT) [ Time Frame: Start of treatment up to end of Cycle 1, Day 21 ] [ Designated as safety issue: Yes ]
Cycle 1 figitumumab attributed: Grade (Gr) 4 neutropenia (absolute neutrophil count <500 cells/cubic millimeter [mm^3]) >=7 days, febrile neutropenia (Gr 3, fever >=38.5 degrees Celsius), neutropenic infection (Gr 3 neutropenia, infection); Gr 4 thrombocytopenia (platelet <25,000 cells/mm^3), Gr 3 thrombocytopenia >=7 days/bleeding; other Gr 3 not blood/bone marrow Common Terminology Criteria for Adverse Events bar gastrointestinal toxicity, treatment-managed hyperglycemia/fatigue, hypersensitivity; Gr 3-4 hyperglycemia despite treatment; fail to adequately recover to continue study treatment
To define the Maximal Tolerated Dose and recommended Phase II dose of CP-751,871 when given in combination with gemcitabine and cisplatin. [ Time Frame: 6-8 months ]
Complete list of historical versions of study NCT00560573 on ClinicalTrials.gov Archive Site
  • Concentration at the End of Infusion (Cinf) for Figitumumab [ Time Frame: Cycle 1 for dose escalation and Cycle 4 for dose expansion ] [ Designated as safety issue: No ]
    Figitumumab pharmacokinetic (PK) data was analyzed using noncompartmental methods
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab [ Time Frame: 0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 1 for dose escation and 0 (pre-dose), 1, 24, 72, 168, 336, 504 hr in Cycle 4 for expansion ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Figitumumab PK data was analyzed using noncompartmental methods
  • Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab [ Time Frame: 0 (pre-dose) in Cycle 5 Day 1 ] [ Designated as safety issue: No ]
    Concentration at the end of Cycle 4
  • Maximum Observed Plasma Concentration (Cmax) for Cisplatin [ Time Frame: 0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2 ] [ Designated as safety issue: No ]
    Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence of (Cycle 2) figitumumab
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin [ Time Frame: 0 (pre-dose), 1.917, 2.5, 3, 4, 5, 24 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 75 mg/m^2 and 0 (pre-dose), 0.917, 1.5, 2, 3, 4, 23 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for cisplatin 80 mg/m^2 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Cisplatin PK data was analyzed using noncompartmental methods. Plasma exposure parameters for cisplatin were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
  • Maximum Observed Plasma Concentration (Cmax) for Gemcitabine [ Time Frame: 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8 ] [ Designated as safety issue: No ]
    Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle) 1 and presence (Cycle 2) of figitumumab
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine [ Time Frame: 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Gemcitabine PK data was analyzed using noncompartmental methods. Plasma exposure parameters for gemcitabine were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
  • Maximum Observed Plasma Concentration (Cmax) for Pemetrexed [ Time Frame: 0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2 ] [ Designated as safety issue: No ]
    Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed [ Time Frame: 0, 0.167, 1.167, 2.167, 4.167, 6.167, 24.167 hr on Cycle 1, Day 1 and Cycle 2, Day 1 for pemetrexed 500 mg/m^2 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pemetrexed PK data was analyzed using noncompartmental methods. Plasma exposure parameters for pemetrexed were analyzed in the absence (Cycle 1) and presence (Cycle 2) of figitumumab
  • Percentage of Participants With Objective Response or Prolonged Stabilization [ Time Frame: Screening, from Cycle 2 onwards computerized tomography (CT) scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose) ] [ Designated as safety issue: No ]
    Percentage of participants with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 12 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST). Participants with non measurable disease were considered having a clinical benefit response only in the case of achievement of CR. Participants who developed early progressive disease post dosing and prior to response evaluation were considered to have progressed on study. Confirmed responses were those that persisted on repeat imaging >= 4 weeks after initial response
  • Progression-Free Survival (PFS) [ Time Frame: Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose) ] [ Designated as safety issue: No ]
    Time from the date of enrollment to date of documented disease progression, or death due to any cause
  • Duration of Response (DR) [ Time Frame: Screening, from Cycle 2 onwards CT scan done within 7-10 days prior to next cycle (approximately Day 15 of each cycle), follow-up (30 days after last study treatment dose) ] [ Designated as safety issue: No ]
    For responding patients (CR and PR): Time from the date that CR or PR was first recorded to the date of the first documentation of progression
  • Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab [ Time Frame: 30 min prior to figitumumab infusion in Cycle 1 and Cycle 4, end of study, fourth follow up visit (approximately 150 days after last dose) ] [ Designated as safety issue: No ]
    Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab
  • Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels [ Time Frame: Baseline, Day 8, end of study ] [ Designated as safety issue: No ]
    To monitor serum total IGF-1 levels as a potential pharmacodynamic response to figitumumab treatment
  • To define the overall safety and tolerability profile of CP-751,871 when given in combination with gemcitabine and cisplatin. [ Time Frame: 6-8 months ]
  • To evaluate the Pharmacokinetics of CP-751,871 in combination with gemcitabine and cisplatin and to monitor serum IGF-1 levels as a potential pharmacodynamic response to CP-751,871 treatment. [ Time Frame: 6-8 months ]
  • evaluate the effect of Rcommended Phase 2 Dose of CP-751,871 on Pharmacokinetics of cisplatin and gemcitabine. [ Time Frame: 6-8 months ]
  • To monitor the occurrence of anti-drug antibody response to CP 751,871. [ Time Frame: 6-8 months ]
  • To monitor for any signs of efficacy of CP-751,871 when given in combination with gemcitabine and cisplatin. [ Time Frame: 6-8 months ]
  • Maximum Tolerated Dose (MTD) [ Time Frame: Cycle 1, up to Day 21 ] [ Designated as safety issue: Yes ]
    The MTD was defined as the highest dose level below the maximum administered dose which caused 0 or 1 out of 6 participants to experience a DLT in that given cohort at Cycle 1
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Baseline to end of dose escalation, which was assessed in the last participant of the dose escalation portion of the study in Month 19 ] [ Designated as safety issue: Yes ]
    The RP2D was determined after review and discussion by sponsor and investigators of the study data. Consideration was given to type and severity of toxicity as well as clinical suitability for long-term administration
Not Provided
 
Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Chemotherapy-Naïve Patients With Advanced Non-Small Cell Lung Cancer
Phase 1, Dose Escalation Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Previously Untreated Patients With Advanced Non-Small Cell Lung Cancer

CP 751,871 is a fully human monoclonal antibody against the Insulin-Like Growth Factor 1 Receptor (IGF-1R). Preclinical and clinical data indicate that CP 751,871 augments the anti-tumor activity of chemotherapy. This study will identify the Maximal Tolerated Dose of CP 751,871 (or the Maximal Feasible Dose) in combination with standard gemcitabine-cisplatin chemotherapy for the treatment of advanced Non-Small Cell Lung cancer.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Non-Small-Cell Lung
  • Drug: CP-751,871
    CP-751,871 at doses ranging from 6 to 20 mg/Kg on Day 1 of each 21-day cycle. CP-751,871 may be administered even after active comparators discontinuation, for a total number of 17 cycles (1 year).
  • Drug: Cisplatin

    Cisplatin 75* mg/m2 or 80* mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycles.

    * 75 mg/m2 when in combination with pemetrexed, 80 mg/m2 when in combination with gemcitabine

  • Drug: Gemcitabine
    Gemcitabine 1250 mg/m2, IV on Days 1 and 8 of each 21-day cycle up to 6 cycles
  • Drug: Pemetrexed
    Pemetrexed 500 mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycle
Experimental: 1
Interventions:
  • Drug: CP-751,871
  • Drug: Cisplatin
  • Drug: Gemcitabine
  • Drug: Pemetrexed
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
March 2010
June 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically or cytologically proven diagnosis of Stage IIIB (N3 and/or T4) or Stage IV Non-Small Cell Lung Cancer in patients 18-year-old or older, with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 not amenable to curative surgery or radiation therapy and an adequate organ function (bone marrow, hepatic, renal, and cardiac) within 14 days prior to enrollment.

Exclusion Criteria:

  • Any prior treatment for Non-Small Cell Lung Cancer including chemotherapy, biologic response modifiers or therapy with any investigational agents.
  • Patients with known brain metastases, spinal cord compression, uncontrolled superior vein cava syndrome or carcinomatous meningitis.
  • Patients with gastrointestinal abnormalities including active gastrointestinal bleeding, pre-diabetes (pre-fasting glycemia > 120 g/dL and/or glycosylate haemoglobin level > 7.5%), known HIV or AIDS-related illness, significant active cardiac disease or receiving chronic steroid therapy or concurrent use of growth hormones or growth hormone inhibitors or aminoglycoside antibiotics should be excluded from the study.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Ireland,   Spain
 
NCT00560573
A4021015
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
March 2013

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