Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
Condition: Large Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer; Bronchioloalveolar Lung Carcinoma
MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar
Intervention: Bevacizumab; Carboplatin; Cixutumumab; Paclitaxel
Intervention description: Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 175.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer; cixutumumab

Summary:

      This randomized phase II trial studies how well carboplatin, paclitaxel, and bevacizumab
      (CPB) work when given with or without cixutumumab in treating patients with non-small cell
      lung cancer that is stage IV or has come back (recurrent). Drugs used in chemotherapy, such
      as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of
      tumor cells to grow and spread. Other types of monoclonal antibodies, such as cixutumumab,
      may find tumor cells and help kill them. It is not yet known whether giving more than one
      drug (combination chemotherapy) together with bevacizumab is more effective when given with
      or without cixutumumab in treating patients with non-small cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed with non-squamous, non-small cell lung
             cancer (NSCLC)

          -  Advanced NSCLC defined as either recurrent disease after prior radiation or surgery or
             stage IV (M1a or M1b) based on the TNM staging system (American Joint Committee on
             Cancer [AJCC] 2009)

          -  Measurable disease as defined by the revised Response Evaluation Criteria in Solid
             Tumors (RECIST version 1.1). All sites of disease (of target and non-target disease
             sites) must be obtained within 4 weeks prior to randomization

          -  A head computed tomography (CT) or magnetic resonance imaging (MRI) required within 4
             weeks prior to randomization

          -  Prior radiation therapy (RT) is allowed if it has been completed 3 weeks prior to
             randomization and patient has recovered from any adverse events related to RT

          -  Brain metastases are allowed, provided they have been treated with surgery and/or
             radiotherapy, the patient is neurologically stable, and repeat brain imaging shows no
             progression in the brain; at least 6 weeks should have elapsed from the time of
             craniotomy and at least 4 weeks from radiotherapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Absolute neutrophil count (ANC) ≥ 1500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Total bilirubin within institutional upper limit of normal (ULN)

          -  Serum creatinine ≤ 1.5 x ULN

          -  Fasting blood glucose within normal range (fasting < 120 mg/dL or below ULN)

          -  Alkaline phosphatase (ALP) ≤ 3 x ULN

          -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN

          -  Urine dipstick must be ≤ 0-1+ within 2 weeks (14 days) of randomization; if urine
             dipstick result is > 1+, a calculation of urine protein creatinine (UPC) ratio is
             required; patients must have a UPC ratio < 1.0 to participate in the study

          -  Neuropathy, if present at baseline, must be ≤ Common Terminology Criteria for Adverse
             Events (CTCAE) grade 1

          -  Patients with a history of hypertension must be well-controlled (≤ 150/90) on a stable
             regimen of anti-hypertensive therapy

          -  Women of childbearing potential and sexually active males should use an accepted and
             effective method of contraception while on treatment and for 3 months thereafter

        Exclusion Criteria:

          -  Prior chemotherapy or biologic/molecular targeted therapy for advanced NSCLC. Prior
             chemotherapy and/or biological/molecular targeted therapy as part of initial
             potentially curative therapy (one regimen of induction and/or adjuvant and/or
             concurrent chemoradiotherapy) was allowed provided it had been completed 1 year or
             more prior to randomization

          -  Prior treatment with IMC-A12 or another insulin-like growth factor 1 receptor (IGF-1R)
             inhibitor

          -  Patients on therapeutic anticoagulation; patient's international normalized ratio
             (INR) must be ≤ 1.5 or partial thromboplastin time (PTT) ≤ upper limits of normal
             within 2 weeks prior to randomization to be eligible; prophylactic anticoagulation of
             venous access devices is allowed provided the above criteria have been met

          -  Prior allergic reaction to compounds of chemical or biologic composition similar to
             those of IMC-A12

          -  Hypersensitivity to any component of bevacizumab

          -  Poorly controlled diabetes mellitus

          -  History of other invasive malignancies unless there is no active disease and all
             treatment has been completed ≥ 3 years prior to randomization; patients with history
             of in-situ malignancies and curatively resected nonmelanomatous skin cancer are
             eligible

          -  History of thrombotic or hemorrhagic disorders

          -  History of bleeding diathesis or coagulopathy

          -  ≥ grade 2 bleeding or any bleeding requiring intervention within 4 weeks prior to
             randomization

          -  History of gross hemoptysis (defined as ≥ 1/2 teaspoon of bright red blood)

          -  Any of the following within 6 months prior to randomization:

               -  Abdominal fistula

               -  Gastrointestinal perforation

               -  Intra-abdominal abscess

               -  Previous myocardial infarction

               -  History of any central nervous system (CNS) cerebrovascular ischemia

               -  New York Heart Association (NYHA) > class II congestive heart failure or severe
                  heart failure

               -  Unstable or symptomatic angina pectoris

               -  History of stroke

               -  Significant vascular disease

               -  Symptomatic peripheral vascular disease

          -  Ongoing, serious cardiac arrhythmia requiring medication at time of randomization

          -  Ongoing, active infection or ongoing fever at the time of randomization or any
             co-existing medical condition, psychiatric illness or limitations that would interfere
             with compliance of study requirements

          -  History of hypertensive crisis or hypertensive encephalopathy

          -  Any of the following within 4 weeks prior to randomization: a serious non-healing
             wound, ulcer, bone fracture, or major surgical procedure

          -  Anticipated major surgical procedure(s) during the course of the study

          -  Receiving daily treatment with aspirin (> 325 mg/day) or non-steroidal
             anti-inflammatory agents (NSAIDs) known to inhibit platelet function for chronic
             conditions; patients must not be receiving treatment with dipyridamole (Persantine),
             ticlopidine (Ticlid), clopidogrel (Plavix), and/or cilostazol (Pletal); if patient was
             receiving any of the following: aspirin (> 325 mg/day), NSAID, and/or anti-platelet
             drugs, patient must have discontinued its use ≥ 1 week prior to randomization

          -  Pregnant or breast-feeding

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy