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

Pfizer46 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

CP-751,871DRUG

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).

CisplatinDRUG

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

GemcitabineDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (4)

Pfizer Investigational Site

Charleroi, Belgium

Pfizer Investigational Site

Dublin, Ireland

Pfizer Investigational Site

Madrid, Madrid, Spain

Pfizer Investigational Site

Seville, Sevilla, Spain

Outcomes

Primary Outcomes

Number of Participants With Dose-limiting Toxicities (DLT)

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

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

Secondary Outcomes

Concentration at the End of Infusion (Cinf) for Figitumumab

Figitumumab pharmacokinetic (PK) data was analyzed using noncompartmental methods

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

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab

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

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

Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab

Concentration at the end of Cycle 4

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

Maximum Observed Plasma Concentration (Cmax) for Cisplatin

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

Data from ClinicalTrials.gov

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

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 Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin

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

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

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 Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine

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

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

Maximum Observed Plasma Concentration (Cmax) for Pemetrexed

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

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 Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed

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

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

Percentage of Participants With Objective Response or Prolonged Stabilization

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

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)

Progression-Free Survival (PFS)

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

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)

Duration of Response (DR)

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

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)

Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab

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

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

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

Time frame: Baseline, Day 8, end of study