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Completed

NCT Number: NCT00560573

Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Chemotherapy-Naïve 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.

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Key information

Conditions

Carcinoma, Non-Small-Cell Lung Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Investigational Site, Charleroi, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

CP-751,871

Drug

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).

Cisplatin

Drug

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

Gemcitabine

Drug

Gemcitabine 1250 mg/m2, IV on Days 1 and 8 of each 21-day cycle up to 6 cycles

Pemetrexed

Drug

Pemetrexed 500 mg/m2, IV on Day 1 of each 21-day cycle up to 6 cycle

Primary outcomes

  1. Number of Participants With Dose-limiting Toxicities (DLT)

    Time frame: Start of treatment up to end of Cycle 1, Day 21

    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

Secondary outcomes

  1. Concentration at the End of Infusion (Cinf) for Figitumumab

    Time frame: Cycle 1 for dose escalation and Cycle 4 for dose expansion

    Figitumumab pharmacokinetic (PK) data was analyzed using noncompartmental methods

  2. 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

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Figitumumab PK data was analyzed using noncompartmental methods

  3. Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab

    Time frame: 0 (pre-dose) in Cycle 5 Day 1

    Concentration at the end of Cycle 4

  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

    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

  5. 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

    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

  6. 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

    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

  7. 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

    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

  8. 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

    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

  9. 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

    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

  10. 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)

    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

  11. 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)

    Time from the date of enrollment to date of documented disease progression, or death due to any cause

  12. 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)

    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

  13. 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)

    Percentage of participants with positive total or neutralizing anti-drug antibody (ADA) for figitumumab

  14. Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels

    Time frame: Baseline, Day 8, end of study

    To monitor serum total IGF-1 levels as a potential pharmacodynamic response to figitumumab treatment

Other outcomes

  1. Maximum Tolerated Dose (MTD)

    Time frame: Cycle 1, up to Day 21

    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

  2. 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

    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

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

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

Important dates

Study start
2007
Primary completion
2008
Study completion
2010
First posted
Nov 19, 2007
Registry last updated
Mar 21, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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