Vandetanib, Carboplatin, and Paclitaxel in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer That Can Be Removed by Surgery
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: carboplatin; paclitaxel; Zactima; neoadjuvant therapy
Intervention description: Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1; Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1.; Zactima- 100 mg orally daily, starting on day 1 of cycle 1.; Neoadjuvant surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Intervention MeSH terms: Paclitaxel; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage IIIA non-small cell lung cancer

Summary:

      RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy,
      such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. Giving vandetanib together
      with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal
      tissue that needs to be removed.

      PURPOSE: This phase II trial is studying how well giving vandetanib together with carboplatin
      and paclitaxel works in treating patients with stage I, stage II, or stage III non-small cell
      lung cancer that can be removed by surgery.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting
             1 of the following staging criteria:

               -  Stage IB or II disease

               -  T3, N0-1 disease (stage IIIA)

          -  Deemed a surgical candidate

          -  No prior lung cancer (NSCLC or small cell lung cancer)

        PATIENT CHARACTERISTICS:

          -  ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

          -  WBC ≥ 3,000/mm³

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Bilirubin normal

          -  AST and ALT ≤ 2.5 times upper limit of normal (ULN)

          -  Creatinine ≤ 1.5 times ULN

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No evidence of severe or uncontrolled systemic disease or any concurrent condition
             that, in the opinion of the investigator, would preclude study compliance

          -  No peripheral neuropathy ≥ grade 2

          -  No hemoptysis within the past 12 weeks

          -  No spontaneous bleeding within the past 12 weeks

          -  No clinically significant cardiac event (e.g., NYHA class II-IV heart disease,
             myocardial infarction) within the past 3 months

          -  No history of asymptomatic sustained ventricular tachycardia or arrhythmia that is
             symptomatic or requires treatment, including any of the following:

               -  Multifocal premature ventricular contractions

               -  Bigeminy

               -  Trigeminy

               -  Ventricular tachycardia

               -  Uncontrolled atrial fibrillation

                    -  Atrial fibrillation controlled with medication allowed

          -  No history of QTc prolongation as a result from other medication that required
             discontinuation of that medication

          -  No congenital long QT syndrome or first-degree family relative with an unexplained
             death before the age of 40

          -  No left bundle branch block

          -  No QTc with Bazett's correction that is unmeasurable or QTc ≥ 480 milliseconds on
             screening ECG

               -  Patients with QTc ≥ 480 milliseconds on screening ECG may have ECG repeated twice

                    -  Average QTc from the 3 screening ECG's must be < 480 milliseconds

          -  No uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg)

          -  No active diarrhea or active gastrointestinal disease that may affect the absorption
             of study drugs or ability to tolerate study drugs

          -  No other malignancy within the past 3 years except in situ cervical carcinoma or
             adequately treated basal cell or squamous cell carcinoma of the skin

        PRIOR CONCURRENT THERAPY:

          -  More than 4 weeks since major surgery and recovered

          -  No prior carboplatin, paclitaxel, or vandetanib

          -  More than 30 days since prior investigational agents

          -  More than 2 weeks since prior and no concurrent drugs that induce CYP3A4 including,
             but not limited to, any of the following:

               -  Rifampin

               -  Phenytoin

               -  Carbamazepine

               -  Barbiturates

               -  Hypericum perforatum (St. John's wort)

          -  No medication that may cause QTc prolongation or induce torsades de pointes for 2
             weeks prior to beginning study treatment, during, and for 2 weeks after completion of
             study treatment

          -  No concurrent combination antiretroviral treatment for HIV-positive patients

          -  No other concurrent investigational agents