A Study of Paclitaxel/Carboplatin With or Without Olaratumab (IMC-3G3) in Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Olaratumab; Paclitaxel; Carboplatin
Intervention description: 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, administered intravenously (IV) at 25 milligram/minute (mg/min), with a minimum infusion time of 30 minutes.; 200 mg/m2 is then administered IV over 3 hours; AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.
Intervention MeSH terms: Paclitaxel; Carboplatin; Olaratumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 137.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung neoplasms; IMC-3G3; carboplatin; paclitaxel; PDGFr

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.
    

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