BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Carboplatin; Pemetrexed; Bevacizumab; Cixutumumab
Intervention description: AUC 6 by vein on day 1 of every 21 day cycle for 4 cycles.; 500 mg/m2 by vein on day 1 of each 21 day cycle.; 15 mg/kg by vein on day 1 of each 21 day cycle.; 20 mg/kg by vein on day 1 of each 21 day cycle.
Intervention MeSH terms: Bevacizumab; Carboplatin; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer; NSCLL; Nonsquamous cell; Metastatic disease; Cixutumumab; IMC-A12; Carboplatin; Paraplatin; Pemetrexed; LY231514; Alimta; MTA; Multitargeted Antifolate; NSC-698037; Bevacizumab; Avastin; Anti-VEGF monoclonal antibody; rhuMAb-VEGF

Summary:

      The goal of this clinical research study is to learn if knowing biomarker status can help
      researchers find better treatment combinations for patients with advanced NSCLC.

      Researchers want to use biomarker status to decide what drug (bevacizumab, or cixutumumab) to
      give in combination with carboplatin and pemetrexed. The safety of these drug combinations
      will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The patient has a diagnosis of pathologically confirmed nonsquamous (nonpredominant
             squamous) NSCLC by tumor biopsy and/or fine-needle aspiration. Mixed tumors will be
             categorized by the predominant cell type; if small cell elements are present, the
             patient is ineligible.

          2. The patient has a diagnosis of either stage IIIB or stage IV NSCLC or has recurrent
             NSCLC and is not a candidate for curative treatment. Patients may not have had
             chemotherapy for the advanced setting.

          3. The patient has measurable NSCLC.

          4. The patient's Eastern Cooperative Oncology Group (ECOG) performance status is </=2 at
             study entry.

          5. The patient should have tumor available for epidermal growth factor receptor (EGFR)
             mutations, ALK fusions and other molecular analyses. If there is no tissue then the
             patient has should have biopsy accessible tumor.

          6. The patient has adequate hematologic function as defined by an absolute neutrophil
             count (ANC) >/= 1,500/mm^3, platelet count >/= 100,000/mm^3, white blood cell count
             (WBC) >/= 3,000/ mm^3, and hemoglobin >/= 9 g/dL.

          7. The patient has adequate hepatic function as defined by a total bilirubin level </=
             1.5 X the upper limit of normal (Serum bilirubin >/= 1.5x Upper Limit of Normal in the
             setting of known Gilbert's disease is allowed), and alkaline phosphatase, AST and ALT
             </= 2.5 X the upper limit of normal or </= 5.0 x ULN if liver metastases are present.

          8. The patient has adequate renal function as defined as CrCl of at least 45ml/min.

          9. If patient has brain metastasis, they must have been stable (treated and/or
             asymptomatic) and off steroids for at least 2 weeks.

         10. The patient is >/= 18 years of age.

         11. The patient has signed informed consent.

         12. Pregnancy Test. Women of childbearing potential must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) for the
             duration of study participation and for six (6) months after discontinuation of the
             study drugs. Childbearing potential will be defined as women who have had menses
             within the past 12 months, who have not had tubal ligation, hysterectomy or bilateral
             oophorectomy. Should a woman become pregnant or suspect that she is pregnant while
             participating in this study, she should inform her treating physician immediately. The
             patient, if a man, agrees to use effective contraception or abstinence for the
             duration of study participation and for six (6) months after discontinuation of the
             study drugs.

         13. The ability to interrupt the use of NSAIDS two days before (5 days for long-acting
             NSAIDs), the day of, and 2 days following administration of Pemetrexed.

        Exclusion Criteria:

          1. The patient has received prior definitive therapy (chemotherapy, surgery, or
             radiotherapy) within 3 months of initiating study drug or within, 2 weeks of localized
             palliative radiotherapy. Patients treated with initial biologic therapy that progress
             are eligible (no drug within 4 weeks). Patients must have recovered from the acute
             toxic effects prior to Day 1 of Cycle 1 to grade </= 1 or baseline.

          2. Patients may not have had prior chemotherapy for first line treatment for NSCLC Stage
             IIIB/IV. Patient with activating EGFR mutations could have been treated with an EGFR
             tyrosine kinase inhibitor. Similarly patient with ALK or ROS1 fusions could have had
             treatment with crizotinib or other ALK inhibitors. Patients may not have had prior
             biologic therapy with antibodies targeting VEGF,or insulin-like growth factor receptor
             (IGFR).

          3. The patient has undergone prior thoracic or abdominal surgery within 30 days of study
             entry, excluding prior diagnostic biopsy.

          4. The patient has a history of uncontrolled angina, arrhythmias, or congestive heart
             failure.

          5. The patient has inadequately controlled hypertension (defined as systolic blood
             pressure > 140 and/or diastolic > 90 mm Hg on antihypertensive medications).

          6. The patient has a history of stroke or transient ischemic attack within 6 months prior
             to Day 1 of Cycle 1.

          7. The patient is unable or unwilling to take folic acid, vitamin B12 supplementation, or
             dexamethasone according to protocol.

          8. The patient has neuropathy >/= grade 2.

          9. The patient has a history of gastrointestinal fistula, perforation, or abscess,
             inflammatory bowel disease, or diverticulitis.

         10. The patient is currently receiving ongoing treatment with full-dose warfarin or
             equivalent (that is, unfractionated and/or low molecular weight heparin).

         11. The patient is pregnant.

         12. The patient is breastfeeding.

         13. Presence of significant third space fluid which cannot be controlled by drainage.

         14. The patient's tumor harbors the EML4-ALK fusion gene.

         15. Drug Specific Eligibility for Treatment Arms. Patients are excluded from the
             Bevacizumab arm if they have a history of hemoptysis (>/= ½ teaspoon of bright red
             blood per episode) within 3 months prior to randomization.

         16. Drug Specific Eligibility for Treatment Arms. Patients are excluded from Bevacizumab
             arm if the Urine Protein Creatinine (UPC) ratio is not within the institutional normal
             limits.

         17. Drug Specific Eligibility for Treatment Arms. Patients are excluded from the IMC-A12
             containing arm if they have poorly controlled diabetes: HBA1C>8% or if the patient has
             abnormally elevated fasting serum glucose (defined >110% ULN).

         18. Drug Specific Eligibility for Treatment Arms. Patients are excluded if they have known
             hypersensitivity to any of the drugs.