Clinical trial NCT00918203: A Study of Paclitaxel/Carboplatin With or Without Olaratumab (IMC-3G3) in Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Lung neoplasms
IMC-3G3
carboplatin
paclitaxel
PDGFr
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-06-11
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if participants with untreated locally advanced or metastatic non-small cell lung cancer have a better outcome when treated with olaratumab in combination with paclitaxel/carboplatin then when treated with paclitaxel/carboplatin alone.

Detailed description: The primary objective of this study is to evaluate the progression-free survival (PFS) in previously untreated participants with Stage IIIB/IV non-small cell lung cancer (NSCLC) treated with olaratumab plus paclitaxel and carboplatin versus paclitaxel and carboplatin in the first-line metastatic setting.

Eligibility criteria: Inclusion Criteria:

1. The participants 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 participant 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 participant 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 participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-1
5. The participant's age at the time of study entry is ≥ 18 years
6. The participant 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 participant 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 participant 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 participant 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 participant 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. Participants 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 Olaratumab 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 participant 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 participant has a life expectancy of ≥ 3 months
14. The participant has provided signed informed consent

Exclusion Criteria:

1. The participant has untreated central nervous system (CNS) metastases. Participants 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 participant has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or of intratumor cavitation
3. The participant received prior systemic chemotherapy or biologic therapy (eg erlotinib) for Stage IIIB/IV NSCLC outside of the adjuvant setting. Participants who received prior cytotoxic chemotherapy or biologic therapy in the adjuvant setting will not be excluded based on such therapy
4. The participant 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 participant 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 participant 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 participant has an uncontrolled thrombotic or hemorrhagic disorder
8. The participant has a history of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months of randomization
9. The participant has a serious non-healing wound, ulcer, or bone fracture within 28 days prior to randomization
10. The participant has undergone major surgery within 28 days prior to randomization
11. The participant 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 participant has an elective or a planned major surgery to be performed during the course of the trial
13. The participant has peripheral neuropathy ≥ Grade 2 NCI-CTCAE v 4.02
14. The participant has known human immunodeficiency virus (HIV) positivity
15. The participant, if female, is pregnant or lactating
16. The participant has received previous therapy with any agent that targets platelet derived growth factor (PDGF) or platelet derived growth factor receptor (PDGFR)
17. The participant has a known allergy to any of the treatment components
18. The participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of Olaratumab

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline to Measured PD or Death From Any Cause (Up to 31 Months)
Secondary outcomes:
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Baseline to Study Completion (Up to 43 Months)
measure: Safety and Tolerability of Olaratumab 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
timeFrame: Up to 43 Months
measure: Overall Survival (OS)
timeFrame: Baseline to Death From Any Cause (Up to 31 Months)
measure: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR)
timeFrame: Baseline to Measured PD or Study Discontinuation (Up to 31 Months)
measure: Median Duration of Response
timeFrame: First Criteria Met for CR or PR to Measured PD Start of Other Antitumor Therapy or Death From Any Cause (Up to 31 Months)
measure: Pharmacodynamics of Olaratumab
timeFrame: Cycle 1: Days 1, 8, and 15 pre- and post-infusion of Olaratumab; Cycles 2-6: day 1 only, pre- and post-infusion of Olaratumab
measure: Percentage of Participants With Anti-Olaratumab Antibodies
timeFrame: Baseline to Study Completion (Up to 8 Months)
measure: Pharmacokinetics (PK) - Area Under the Curve (AUC) 0-168 of Olaratumab
timeFrame: Cycle 3, Day 1: Predose, 30 minutes (min), 1.5 hours (hrs), 24,48,96,168 Hrs Post Dose
measure: PK - Maximum Concentration (Cmax) of Olaratumab
timeFrame: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose
measure: PK - Half-Life (t1/2) of Olaratumab
timeFrame: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose
measure: PK - Clearance (Cl) of Olaratumab
timeFrame: Cycle 3, Day 1: Predose, 30 min, 1.5 hr, 24,48,96,168 Hrs Post Dose
measure: PK - Steady State Volume of Distribution (Vss) of Olaratumab
timeFrame: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: ImClone Investigational Site
state: Alabama
city: Bakersfield
country: United States
facility: ImClone Investigational Site
state: California
city: Highland
country: United States
facility: ImClone Investigational Site
state: California
city: Stamford
country: United States
facility: ImClone Investigational Site
state: Connecticut
city: Port Saint Lucie
country: United States
facility: ImClone Investigational Site
state: Florida
city: Joliet
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Baton Rouge
country: United States
facility: ImClone Investigational Site
state: Louisiana
city: Saint Louis
country: United States
facility: ImClone Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Gastonia
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Huntersville
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Canton
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Massillon
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Portland
country: United States
facility: ImClone Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: ImClone Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: ImClone Investigational Site
state: Texas
city: Round Rock
country: United States
facility: ImClone Investigational Site
state: Texas
city: Temple
country: United States
facility: ImClone Investigational Site
state: Texas
city: Madison
country: United States
facility: ImClone Investigational Site
state: Wisconsin
city: Calgary
country: Canada
facility: ImClone Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: ImClone Investigational Site
state: Alberta
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: