Carboplatin, Pemetrexed Disodium, and Bevacizumab for Patients With Stage III or IV Non-Small Cell Lung Cancer Who Are Light/Never Smokers
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: bevacizumab; carboplatin; erlotinib hydrochloride; pemetrexed disodium
Intervention description: 15 mg/kg once per 21 day cycle (up to 4 cycles).; Area Under the Curve (AUC)=6, once every 21 day cycle (up to 4 cycles); 150mg, daily for 21 day cycle (up to 4 cycles); 500 mg/m2 on day 1 of a 21 day cycle (up to 4 cycles)
Intervention MeSH terms: Bevacizumab; Carboplatin; Pemetrexed; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop
      the growth of non-small cell lung cancer by blocking blood flow to the tumor. Giving
      carboplatin and pemetrexed disodium together with bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving carboplatin and pemetrexed disodium
      together with bevacizumab works in treating patients with stage III or stage IV non-small
      cell lung cancer who are light or never smokers.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed primary lung carcinoma

               -  Non-squamous histology

               -  Advanced disease defined as stage IIIB disease with cytologically documented
                  malignant pleural or pericardial effusion or stage IV disease

          -  Available pathology block or unstained slides from initial or subsequent diagnosis

               -  Must have undergone ≥ 1 core biopsy

               -  No patients whose diagnosis was made through a fine-needle aspirate

          -  No uncontrolled pleural effusions, ascites, or third-space fluid collections

          -  Meets 1 of the following criteria:

               -  Non-smoker, defined as patients who smoked ≤ 100 cigarettes in their lifetime

               -  Former light smoker, defined as patients who smoked between > 100 cigarettes AND
                  ≤ 10 pack-years AND quit ≥ 1 year ago

          -  No known central nervous system disease, except for treated brain metastases meeting
             the following criteria:

               -  No evidence of progression or hemorrhage after treatment

               -  No ongoing requirement for dexamethasone as ascertained by clinical examination
                  and brain imaging (MRI or CT scan) during the screening period

               -  Stable doses of anticonvulsants are allowed

               -  Treatment for brain metastases may include whole-brain radiotherapy, radiosurgery
                  (gamma knife, LINAC, or equivalent), or a combination as deemed appropriate by
                  the treating physician

               -  No patients with central nervous system (CNS) metastases treated by neurosurgical
                  resection

               -  No brain biopsy within the past 3 months

        PATIENT CHARACTERISTICS:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Absolute neutrophil count (ANC) ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Hemoglobin ≥ 9.0 g/dL

          -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST/ALT) ≤ 2.5 times ULN

          -  Calculated creatinine clearance > 45 mL/min OR creatinine ≤ 1.5 times ULN

          -  Prothrombin time ≤ 1.5 times ULN

          -  Partial thromboplastin time ≤ ULN

          -  Urine protein:creatinine ratio ≤ 1.0

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Patients with a history of hypertension are eligible provided it is well controlled
             (BP < 150/100 mm Hg) on a stable regimen of antihypertensive therapy

               -  No history of hypertensive crisis or hypertensive encephalopathy

          -  Able and compliant with folic acid and B12 supplementation

          -  Able to swallow tablets intact or dissolved in water

          -  No dysphagia or active gastrointestinal (GI) disease or disorder that alters GI
             motility or absorption

          -  No lack of integrity of the GI tract (e.g., a significant surgical resection of the
             stomach or small bowel)

          -  No abdominal fistula, GI perforation, or intraabdominal abscess within the past 6
             months

          -  None of the following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure (NYHA class II-IV)

               -  Cardiac arrhythmia

               -  Psychiatric illness, social situations, or any other medical condition that would
                  limit compliance with study requirements

          -  No myocardial infarction or other evidence of arterial thrombotic disease (angina)
             within the past 6 months

          -  No history of cerebral vascular accident or transient ischemic attack within the past
             6 months

          -  No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
             recent peripheral arterial thrombosis) within the past 6 months

          -  No history of bleeding diathesis or coagulopathy

          -  No ongoing hemoptysis, defined as ≥ ½ teaspoon of bright red blood

               -  Patients with procedure-related hemoptysis that has resolved post-procedure are
                  eligible

          -  No serious nonhealing wound, ulcer, bone fracture, or significant traumatic injury
             within the past 28 days

          -  No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

        PRIOR CONCURRENT THERAPY:

          -  No prior chemotherapy

               -  Patient must be chemotherapy naive

               -  Prior neoadjuvant or adjuvant chemotherapy allowed provided it was completed ≥ 6
                  months ago

          -  No prior anti-vascular endothelial growth factor therapy

          -  At least 3 weeks since prior major surgery

          -  At least 1 week since prior radiotherapy

          -  More than 28 days since prior and no concurrent treatment with an investigational
             agent

          -  More than 7 days since prior core biopsy

          -  Concurrent daily treatment with aspirin or NSAIDs are eligible provided patients are
             able to interrupt NSAIDs 2 days before (5 days for long-acting NSAIDs), the day of,
             and for 2 days following the administration of pemetrexed disodium

          -  No concurrent treatment with dipyridamole (Persantine), ticlopidine (Ticlid),
             clopidogrel (Plavix), and/or cilostazol (Pletal)