Phase 2 Trial of Bevacizumab in Combination With Pemetrexed
Condition: Non-small Cell Lung Cancer (NSCLC); Lung Cancer; Neoplasm Metastasis
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis
Intervention: Bevacizumab; Pemetrexed; Vitamin B12; Folate; Dexamethasone
Intervention description: 15 mg/kg, IV over 10 minutes every 3 weeks; 500 mg/m²; IV over 10 minutes every 3 weeks; 1000 micrograms, IM injection 1-2 weeks prior to treatment and repeated every 9 weeks until last dose of pemetrexed; 350 to 1000 micrograms 1 week prior to treatment and 3 weeks after last pemetrexed dose; 4 mg; oral, twice a day at the following times: the day before, of and after each dose of pemetrexed
Intervention MeSH terms: Vitamins; Folic Acid; Vitamin B 12; Vitamin B Complex; Dexamethasone; Bevacizumab; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial evaluated the safety of combining bevacizumab and pemetrexed in non-small cell
      lung cancer (NSCLC) patients with stable brain metastases as second-line chemotherapy, while
      evaluating progression-free survival (PFS) and overall survival (OS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Advanced stage NSCLC excluding squamous cell histology with measurable or evaluable
             disease.

          -  Stable brain metastases required, no longer requiring active therapy such as steroid
             medications, which have been previously treated with radiation or surgery or both and
             have been documented to be stable on repeat imaging done at least one month after
             completion of therapy.

          -  Prior therapy with one standard doublet front-line regimen for NSCLC (platinum
             containing)

          -  Life expectancy of at least 3 months

          -  ECOG Performance status 0-1

          -  Age 18 or higher

          -  Use of effective means of contraception (men and women) in subjects of child-bearing
             potential

          -  Ability/willingness to comply with vitamin supplementation including vitamin B 12 and
             folic acid started at least 1 week before first dose of pemetrexed and continued for
             at least 3 weeks after last dose

          -  Ability/willingness to take dexamethasone the day before, of and after pemetrexed
             administration

          -  Drainage of any clinically significant effusion

          -  Ability to sign informed consent

        Exclusion Criteria:

          -  Treatment with more than one prior chemotherapy regimen (unless one regimen was
             stopped for toxicity reasons with a different regimen replacement regimen started
             immediately and patient completed only 4-6 total cycles of first-line treatment. One
             prior regimen (up to 4 cycles) of neoadjuvant or adjuvant therapy for early stage
             disease will also be allowed.

          -  Prior treatment with pemetrexed or bevacizumab

          -  Prior chemotherapy within 28 days (6 weeks for BCNU, CCNU or mitomycin-C)

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in any other experimental drug study

          -  Concomitant chemotherapy, radiotherapy or investigational agents

          -  Uncontrolled effusion (large pleural or peritoneal effusion or small/moderate effusion
             which requires drainage for symptom management)

          -  Evidence of bleeding diathesis or coagulopathy

          -  Use of anti-coagulant agents including warfarin, heparin, aspirin, NSAIDs

          -  Pregnant (positive pregnancy test) or lactating women

          -  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, fine needle aspirations or core biopsies within 7 days
             prior to day 0

          -  Urine protein:creatinine ratio greater than or equal to 1.0 at screening

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Day 0

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Lung carcinoma of squamous cell histology or any histology in close proximity to a
             major vessel, or with significant cavitation as assessed by treating investigator in
             consultation with an attending radiologist

          -  History of hemoptysis (bright red blood of 1/2 teaspoon or more)

          -  Neutrophils < 1.5 x 10^9/ L

          -  Hemoglobin <10.0 g/dl

          -  Platelets <100 x 10^9/ L

          -  Serum glutamic oxaloacetic transaminase (SGOT/ AST) or serum glutamic pyruvic
             transaminase (SGPT/ ALT) > 2.5 times upper limits of normal

          -  Creatinine > 1.5 times upper limits of normal

          -  Significant co-morbidities including:

               -  Blood pressure of greater than 150/100 mmHg

               -  Unstable angina

               -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

               -  History of myocardial infarction within 6 months

               -  History of stroke within 6 months

               -  Clinically significant peripheral vascular disease

          -  Inability to comply with study and/or follow-up procedures