Pemetrexed Disodium, Gemcitabine, and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: bevacizumab; gemcitabine hydrochloride; pemetrexed disodium
Intervention description: Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days; Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days; Pemetrexed disodium 400 mg/m2 intravenously over 10 minutes every 14 days.
Intervention MeSH terms: Bevacizumab; Gemcitabine; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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; recurrent non-small cell lung cancer

Summary:

      RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. 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 tumor cells by blocking blood flow to the tumor. Giving pemetrexed disodium and
      gemcitabine together with bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving pemetrexed disodium and gemcitabine
      together with bevacizumab works in treating patients with stage IIIB or stage IV non-small
      cell lung cancer.
    

Eligibility criteria:

        Inclusion Criteria

          -  Histologic or cytologic proof of non-squamous non-small cell lung cancer (NSCLC)
             (adenocarcinoma, bronchioloalveolar, large cell carcinoma).

          -  Must have Stage IV or IIIB NSCLC. Patients with Stage IIIB must have a pleural
             effusion or not be candidates for treatment for locally advanced disease with
             chemoradiotherapy.

          -  Cannot have a tumor with cavitation..

          -  Have uni-dimensional measurable or evaluable disease. If disease is within a previous
             radiation port there must be documented progression.

          -  18 years of age and have a life expectancy of greater than 12 weeks.

          -  Must not have had prior chemotherapy for advanced disease.

          -  Must have an ECOG performance status of 0-1.

          -  With treated brain metastases are eligble. for details.

          -  Adequate organ function:

        Absolute neutrophil count of > 1.5 x 109/L Platelet count > 100,000/109/L Hemoglobin >
        8g/dl Calculated creatinine clearance > 45mL/min using the standard Cockroft and Gault
        formula Hepatic: bilirubin < 1.5 times the upper limit of normal,alkaline phosphatase,
        aspartate transaminase (AST) and alanine transaminase (ALT) < 3 times upper limit of
        normal. Alkaline phosphatase, AST, ALT < 5 times upper limit of normal is acceptable if
        liver has tumor involvement. Urine protein:creatinine ratio ≤1.0 at screening

          -  Patients of reproductive potential must use an approved contraceptive method during
             and for 3 months after study.

          -  Must sign an informed consent that details the investigational nature of the study
             according to the institutional and federal guidelines.

          -  Registered with the clinical trials office of the institution.

        Exclusion Criteria

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study other than a Genentech-sponsored
             bevacizumab cancer study

          -  Prior chemotherapy except for erlotinib for advanced disease.

          -  Uncontrolled hypertension (Blood pressure of >150/100 mmHg )

          -  Unstable angina

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure (see
             Appendix E)

          -  History of myocardial infarction within 6 months prior to day 1

          -  History of hemorrhagic or thrombotic stroke or other CNS bleed within 6 months prior
             to day 1

          -  Clinically significant peripheral vascular disease of 61

          -  Evidence of bleeding diathesis or coagulopathy. Patients must not require full dose
             anticoagulants for any reason.

          -  Known CNS disease, except for treated brain metastasis Treated brain metastases are
             defined as having no evidence of progression or hemorrhage after treatment and no
             ongoing requirement for dexamethasone, as ascertained by clinical examination and
             brain imaging (MRI or CT) during the screening period.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0, anticipation of need for major surgical procedure during the course of
             the study

          -  Minor surgical procedures such as fine needle aspirations or core biopsies within 7
             days prior to Day 0

          -  Urine protein:creatinine ratio > or = 1.0 at screening

          -  History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
             within 6 months prior to Day 0

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Evidence of cavitation in the tumor.

          -  Intrathoracic lung carcinoma of squamous cell histology Mixed tumors will be
             categorized by the predominant cell type unless small cell elements are present, in
             which case the patient is ineligible; sputum cytology alone is unacceptable.

          -  Extrathoracic-only squamous cell NSCLC are eligible. Patients with only peripheral
             lung lesions (of any NSCLC histology) will also be eligible.

          -  History of hemoptysis (bright red blood of 1/2 teaspoon or more within 28 days of
             registration or clinical history of > Grade 2

          -  Clinically significant effusions that cannot be drained

          -  Inability to comply with study and/or follow-up procedures

          -  Previous or concurrent malignancies with the exception of adequately treated squamous
             cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any
             other malignancy treated and in clinical remission for more than 3 years.

          -  Prior radiation therapy to the target lesion, unless the lesion is clearly progressing
             and the interval between the most recent radiation therapy and enrollment is at least
             4 weeks.

          -  Pregnancy or lactating females. All pre-menopausal women should have a negative urine
             pregnancy test prior to enrollment. All patients of reproductive potential should
             agree to use an effective contraceptive method.

          -  Serious concomitant systemic disorders (including oncologic emergencies) incompatible
             with the study (at the discretion of the investigator).

          -  Inability to interrupt non-steroidal anti-inflammatory agents 2 days before, the day
             of, and 2 days after the dose of pemetrexed.

          -  Disease which cannot be radiologically imaged.

          -  Inability to take dexamethasone, folic acid or vitamin B12 administration.