Study of Oxaliplatin and Gemcitabine With or Without Bevacizumab to Treat Advanced Non-Small Cell Lung Cancer
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      The combination of oxaliplatin and gemcitabine has proven activity in advanced non-small cell
      lung cancer (NSCLC). Due to its favorable toxicity profile, this combination is optimal for
      adding new agents. Bevacizumab is an anti-VEGF monoclonal antibody that has also shown
      favorable results in advanced NSCLC. This study will add bevacizumab to oxaliplatin and
      gemcitabine as first line treatment in patients with Stage IIIB and IV NSCLC.
    

Detailed description: 
      STUDY OBJECTIVES:

      Primary:

      To determine the overall time to progression of the combination regimen of Gemcitabine,
      Oxaliplatin and Bevacizumab as first-line treatment in patients with Stage IIIB and IV
      non-small cell lung cancer.

      Secondary

        -  To determine the overall response rate

        -  To determine the overall survival.

        -  To determine the toxicity of Gemcitabine, Oxaliplatin given in combination with
           Bevacizumab

      ELIGIBILITY CRITERIA

        1. Patients must have histologically or cytologically confirmed non-small cell lung cancer
           EXCEPT squamous cell carcinoma. Mixed tumors will be categorized by the predominant cell
           type unless small cell elements are present in which case the patient is ineligible.
           Cytologic or histologic elements can be established on metastatic tumor aspirates or
           biopsy.

        2. Patients must have advanced NSCLC (Stage IIIB with malignant pleural effusion or Stage
           IV or recurrent disease).

        3. Patients must have measurable disease (as defined in Section 13.0).

        4. ECOG performance status 0 or 1.

        5. Patients must not have known CNS metastases. Brain imaging is required within 4 weeks
           prior to study entry.

        6. No prior systemic treatment for advanced NSCLC is permitted. Prior treatment for
           early-stage disease (adjuvant) or for locally-advanced Stage III disease is allowed if
           completed at least 12 months prior to registration.

        7. Required laboratory values (obtained 2 weeks prior to registration):

           7.1 ANC > 1500/mm³. 7.2 Platelets > 100,000/mm³. 7.3 Total Bilirubin < 1.5 mg/dl. 7.4
           Transaminases < 5 x ULN.

        8. Patients must have adequate renal function as determined by the following tests within 2
           weeks prior to registration.

           8.1 Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN), AND
           Urinalysis < 1+ protein*

           * Patients discovered to have >1+ proteinuria at baseline must undergo a 24-hour urine
           collection. This must be an adequate collection and must demonstrate <1g of protein/24
           hr to allow participation in the study.

        9. Patients must be 18 years or older.

       10. Pregnant and lactating women are excluded from the study because the agents used in this
           study may be teratogenic to a fetus and there is no information on the excretion of the
           agents or their metabolites into breast milk. A negative urine or serum pregnancy test
           required for women of childbearing potential.

       11. Women of childbearing potential and sexually active males must agree to use an accepted
           and effective method of contraception (hormonal or barrier methods, abstinence) prior to
           study entry and for the duration of the study.

       12. Patients treated with radiation therapy must have adverse events from therapy resolved
           to grade 2 or less following completion of treatment.

       13. Patients must not have ongoing or active infection, symptomatic congestive heart
           failure, cerebrovascular accident within 12 months, unstable angina pectoris, cardiac
           arrhythmia, or psychiatric illness/social situations that would limit compliance with
           study requirements.

       14. Patients must have no deep vein thrombosis or pulmonary embolus within one year of
           registration and no ongoing need for full-dose oral or parenteral anticoagulation. Low
           dose coumadin (1mg) for maintenance of catheter patency or daily prophylactic aspirin is
           allowed.

       15. Patients with history of hypertension must be well-controlled (defined as a blood
           pressure of >160 mmHg systolic and/or > 110 mmHg diastolic) on a stable regimen of
           anti-hypertensive therapy.

       16. Patients must not have serious non-healing wound ulcer, or bone fracture, or major
           surgical procedure within 3 weeks prior to starting treatment.

       17. Patients with a history of gross hemoptysis (defined as bright red blood of a ½ teaspoon
           or more) will be excluded from this trial

       18. No prior malignancy is allowed except for adequately treated basal cell or squamous cell
           skin cancer, in situ cervical cancer, or other cancer for which the patient has been
           disease-free for five years

      TREATMENT PLAN Gemcitabine 1000mg/m2 IV over 30 minutes, on days 1 and 8 followed by
      Oxaliplatin 130mg/m2 IV over 2 hours on day 1 followed by Bevacizumab 15 mg/kg IV over 90*
      minutes, on day 1 Cycles q 3 weeks x 4 cycles One cycle equals 3 weeks. Patients will be
      re-evaluated every 2 cycles. If CR, PR or SD, patients will continue treatment up to four
      cycles or until progression or unacceptable toxicity.

      Patients achieving CR, PR, or SD after 4 cycles will continue Bevacizumab maintenance:

      Bevacizumab 15 mg/kg IV q 3 weeks until relapse/progression
    

Intervention name(s): oxaliplatin, gemcitabine, bevacizumab
Intervention type(s): Drug
Intervention description(s): Gemcitabine 1000mg/m2 IV over 30 minutes, on days 1 and 8 followed by Oxaliplatin 130mg/m2 IV over 2 hours on day 1 followed by Bevacizumab 15 mg/kg IV over 90* minutes, on day 1 Cycles q 3 weeks x 4 cycles One cycle equals 3 weeks. Patients will be re-evaluated every 2 cycles. If CR, PR or SD, patients will continue treatment up to four cycles or until progression or unacceptable toxicity.
Patients achieving CR, PR, or SD after 4 cycles will continue Bevacizumab maintenance:
Bevacizumab 15 mg/kg IV q 3 weeks until relapse/progression
Intervention MeSH terms: Bevacizumab; Gemcitabine; Oxaliplatin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment