Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatments imc-3g3, paclitaxel, carboplatin
Phase phase 2
Target PDGF
Sponsor Eli Lilly and Company
Start date January 2010
End date August 2013
Trial size 137 participants
Trial identifier NCT00918203, 13900, CP15-0804, I5B-IE-JGDB

Summary

The purpose of this study is to determine if patients with untreated locally advanced or metastatic non-small cell lung cancer have a better outcome when treated with IMC-3G3 in combination with paclitaxel/carboplatin then when treated with paclitaxel/carboplatin alone.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
(Initial 4-6 cycles) Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle (Initial 4-6 cycles) Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Patients who experience progressive disease may cross over to IMC-3G3 monotherapy.
paclitaxel
200 mg/m2 is then administered I.V. over 3 hours
carboplatin
AUC=6 administered I.V. over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of paclitaxel/carboplatin are reached the patient may continue on IMC-3G3 maintenance for up to 12 months.
(Experimental)
(Initial 4-6 cycles) IMC-3G3 15 mg/kg over 30 mins (Days 1 and 8) plus Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Patients can remain on study after completing chemotherapy and receive IMC- 3G3 monotherapy on Days 1 and 8, provided there is ongoing evidence of clinical benefit.
imc-3g3 LY3012207
15 mg/kg of IMC-3G3 on Days 1, 8, and 15 of each 21-day cycle, administered as an I.V. infusion at 25mg/min, with a minimum infusion time of 30 minutes.
paclitaxel
200 mg/m2 is then administered I.V. over 3 hours
carboplatin
AUC=6 administered I.V. over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of paclitaxel/carboplatin are reached the patient may continue on IMC-3G3 maintenance for up to 12 months.

Primary Outcomes

Measure
Progression-Free Survival
time frame: Approximately week 18

Secondary Outcomes

Measure
Safety Profile in each arm, determined by number of Participants with Adverse Events
time frame: Approximately week 18
Safety and tolerability of IMC-3G3 administered at a more rapid rate (25mg/min with minimum infusion time of 30 minutes), determined by number of participants with treatment related Adverse Events
time frame: Approximately week 18
Radiographic objective response rate (ORR) determined by Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: Approximately week 18
Overall survival (OS)
time frame: Approximately week 18
Median duration of response
time frame: Approximately week 18
Pharmacodynamic profile of IMC-3G3, determined by analysis of pharmacodynamic markers VEGF and PDGF
time frame: Approximately Week 12
Immunogenicity of IMC-3G3, determined by Anti-IMC-3G3 antibody sampling
time frame: Approximately Week 12
Pharmacokinetics - Area under the curve (AUC) of IMC-3G3 for participants in Experimental Arm
time frame: Approximately Week 12
Pharmacokinetics - Maximum concentration (Cmax) of IMC-3G3 for participants in Experimental Arm
time frame: Approximately Week 12
Pharmacokinetics - Half-Life (t1/2) of IMC-3G3 for participants in Experimental Arm
time frame: Approximately Week 12
Pharmacokinetics - Clearance (Cl) of IMC-3G3 for participants in Experimental Arm
time frame: Approximately Week 12
Pharmacokinetics - Steady State Volume of Distribution (Vss) of IMC-3G3 for participants in Experimental Arm
time frame: Approximately Week 12

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. The patient has histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC)Stage IIIB with effusion. Mixed Non-Small Cell Lung Cancer (NSCLC) tumors will be categorized by the predominant cell type. Primary or metastatic site may be used for histology 2. For squamous cell histology or for centrally located mediastinal masses (< 3 cm from the carina) identified by computed tomography scan (CT) or chest x-ray, the patient must undergo a magnetic resonance imaging (MRI) of the chest or I.V. contrast CT scan within 3 weeks of randomization, to exclude major airway or blood vessel invasion (in the investigator's opinion) by cancer 3. The patient has measurable disease (Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy 4. The patient's Eastern Cooperative Oncology Group (ECOG) performance status is 0-1 5. The patient's age at the time of study entry is ≥ 18 years 6. The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9.5 g/dL, and a platelet count ≥ 100,000/μL obtained within 2 weeks prior to randomization 7. The patient has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × the upper limit of normal ([ULN], or ≤ 5 × the ULN in the presence of known liver metastases) 8. The patient has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the patient's creatinine clearance (CrCl) is ≥ 60 mL/min 9. The patient has urinary protein ≤ 1+ on dipstick or routine urinalysis; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1 g of protein in 24 hours to allow participation 10. The patient has adequate coagulation function, as defined by international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN if not receiving anticoagulation therapy. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin, have therapeutic INR, no active bleeding (defined as within 14 days randomization) and no pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices) 11. Because the teratogenicity of IMC-3G3 is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to randomization and for the duration of study participation 12. The patient has resolution to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4 (NCI-CTCAE v 4.02) of all clinically significant toxic effects of prior locoregional therapy, surgery, chemoembolization, or other anticancer therapy. The exceptions for such effects are events that pertain to the lab values found elsewhere in these inclusion criteria. (For example, criterion # 6 states that a patient with hemoglobin ≥ 9.5 g/dL is considered eligible, even though NCI-CTCAE v 4.02 defines this value as Grade 2 anemia.) 13. The patient has a life expectancy of ≥ 3 months 14. The patient has provided signed informed consent Exclusion Criteria: 1. The patient has untreated central nervous system (CNS) metastases. Patients are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radiosurgery)ending at least 2 weeks prior to randomization, or after surgical resection performed at least 4 weeks prior to randomization 2. The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or of intratumor cavitation 3. The patient received prior systemic chemotherapy or biologic therapy (eg erlotinib) for Stage IIIB/IV NSCLC outside of the adjuvant setting. Patients who received prior cytotoxic chemotherapy or biologic therapy in the adjuvant setting will not be excluded based on such therapy 4. The patient has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous skin cancer b) curatively treated cervical carcinoma in situ c)other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to randomization 5. The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent 6. The patient has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 7. The patient has an uncontrolled thrombotic or hemorrhagic disorder 8. The patient has a history of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months of randomization 9. The patient has a serious non-healing wound, ulcer, or bone fracture within 28 days prior to randomization 10. The patient has undergone major surgery within 28 days prior to randomization 11. The patient has received adjuvant chemotherapy 21 days prior to randomization or has participated in clinical trials of experimental agents within 28 days prior to randomization 12. The patient has an elective or a planned major surgery to be performed during the course of the trial 13. The patient has peripheral neuropathy ≥ Grade 2 NCI-CTCAE v 4.02 14. The patient has known human immunodeficiency virus (HIV) positivity 15. The patient, if female, is pregnant or lactating 16. The patient has received previous therapy with any agent that targets PDGF or PDGFR 17. The patient has a known allergy to any of the treatment components 18. The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-3G3

Additional Information

Official title A Randomized Phase 2 Study of Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) With Paclitaxel/Carboplatin or Paclitaxel/Carboplatin Alone in Previously Untreated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Description The primary objective of this study is to evaluate the progression-free survival (PFS) in previously untreated patients with Stage IIIB/IV non-small cell lung cancer (NSCLC) treated with IMC-3G3 plus paclitaxel and carboplatin versus paclitaxel and carboplatin in the first-line metastatic setting.
Trial information was received from ClinicalTrials.gov and was last updated in May 2014.
Information provided to ClinicalTrials.gov by Eli Lilly and Company.