Clinical trial NCT00560573: Study Of CP-751,871 In Combination With Cisplatin And Gemcitabine In Chemotherapy-Naïve Patients With Advanced Non-Small Cell Lung Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-11-19
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLT)
timeFrame: Start of treatment up to end of Cycle 1, Day 21
Secondary outcomes:
measure: Concentration at the End of Infusion (Cinf) for Figitumumab
timeFrame: Cycle 1 for dose escalation and Cycle 4 for dose expansion
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Figitumumab
timeFrame: 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
measure: Minimum Observed Plasma Trough Concentration (Cmin) for Figitumumab
timeFrame: 0 (pre-dose) in Cycle 5 Day 1
measure: Maximum Observed Plasma Concentration (Cmax) for Cisplatin
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Cisplatin
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) for Gemcitabine
timeFrame: 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Gemcitabine
timeFrame: 0 (pre-dose), 0.417, 1, 1.5, 2.5, 3.5 hr on Cycle 1, Day 1 and Cycle 2, Day 8
measure: Maximum Observed Plasma Concentration (Cmax) for Pemetrexed
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Pemetrexed
timeFrame: 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
measure: Percentage of Participants With Objective Response or Prolonged Stabilization
timeFrame: 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)
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Duration of Response (DR)
timeFrame: 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)
measure: Percentage of Participants With Blood Anti-drug Antibody (ADA) Specific for Figitumumab
timeFrame: 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)
measure: Serum Total Circulating Insulin-like Growth Factor (IGF-1) Levels
timeFrame: Baseline, Day 8, end of study
Other outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Cycle 1, up to Day 21
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Baseline to end of dose escalation, which was assessed in the last participant of the dose escalation portion of the study in Month 19
Locations:
city: Charleroi
country: Belgium
facility: Pfizer Investigational Site
city: Dublin
country: Ireland
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
city: Sevilla
country: Spain
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: