Carboplatin, Bevacizumab and Pemetrexed in Advanced Non Small Cell Lung Cancer
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Carboplatin, Pemetrexed and Bevacizumab
Intervention description: Carboplatin AUC 5 IV day 1 over 30-60 minutes Pemetrexed 500 mg/M2 IV day 1 over 10 minutes Bevacizumab 15 mg /kg IV day over 90 minutes dose 1, 60 minutes dose 2, 30 minutes subsequent doses. Repeat every 3 weeks for total of 6 cycles
Intervention MeSH terms: Bevacizumab; Carboplatin; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to look for an improvement in progression free survival with the
      combination of bevacizumab, carboplatin and pemetrexed in patients with newly diagnosed
      advanced/metastatic non small cell lung cancer. Overall survival and safety will also be
      assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Advanced stage NSCLC (IIIB with malignant pleural effusion; T4 [on basis on satellite
             lesion] N2, 3; or stage IV) excluding squamous cell histology, with measurable or
             evaluable disease.

          -  Prior chemotherapy therapy for early stage disease with one regimen is acceptable if
             it was completed at least 6 months prior to study entry.

          -  Palliative radiotherapy to painful bony metastases will be permitted prior to study
             entry if completed prior to initiation of study treatment, and there are no residual
             sequelae of therapy such as bone marrow suppression.

          -  Life expectancy of at least 3 months.

          -  ECOG Performance status 0-1.

          -  Age 18 or higher.

          -  Willingness to use appropriate contraception to avoid pregnancy during the study
             (female patient or female partner of a male patient)

          -  Patients must have normal organ and marrow function as defined below:

        leukocytes greater than or equal to3,000/µl ANC greater than or equal to 1,500/µl platelets
        greater than or equal to 100,000/µl total bilirubin within normal institutional limits
        AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal creatinine within normal
        institutional limits OR creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with
        creatinine levels above institutional normal

          -  Ability to sign informed consent

          -  Ability to take folic acid, Vitamin B12 and dexamethasone as per protocol

          -  Ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of,
             and 2 days following administration of Alimta.

        Exclusion criteria

        Patients meeting any of the following criteria are ineligible for study entry:

          -  Prior cytotoxic treatment for advanced NSCLC. One prior regimen (up to 4 cycles) of
             neoadjuvant or adjuvant therapy for early stage disease will be allowed if completed
             at least 6 months prior to study entry.

          -  Prior definitive chest irradiation (radiation of rib or spine mets permitted)

          -  Known brain metastases (unless previously resected and radiated)

          -  Prior treatment with bevacizumab or pemetrexed

          -  History of allergic reactions or sensitivity attributed to compounds of similar
             chemical or biologic composition to bevacizumab or carboplatin

          -  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.

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Use of anti-coagulant agents warfarin (1mg, by mouth, daily for port maintenance
             permitted), heparin (ASA, NSAID permitted).

          -  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 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. -Recent history of hemoptysis (bright red
             blood of 1/2 teaspoon or more)- within one month of study entry

          -  Significant co-morbidities including:

        Blood pressure of 150/100 mmHg Unstable angina New York Heart Association (NYHA) Grade II
        or greater congestive heart failure (see Appendix B) History of myocardial infarction
        within 6 months History of stroke within 6 months Clinically significant peripheral
        vascular disease

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Another active malignancy except for non-melanoma skin cancers.

          -  Clinically significant pleural, pericardial, and/or peritoneal effusions unless
             drained or controlled prior to study entry.

          -  Undrainable, clinically relevant effusions and presence of third space fluid which
             cannot be controlled by drainage.

          -  Hepatic impairment as evidenced by Bilirubin greater than 1.5 times the upper limit of
             normal Transaminases greater than 3.0 times limit of normal (ULN), except in presence
             of known hepatic metastasis, wherein may be up to 5 times ULN

          -  Any CTCAE Version 3.0 Grade 3 or 4 non hematologic toxicity