Phase II Study Alimta and Gemzar + Avastin as First Line Chemotherapy for Elderly Patients With Stage IIIB/IV NSCLC
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pemetrexed and Gemcitabine plus Bevacizumab
Intervention description: Bevacizumab 10 mg/kg will be given intravenously according to weight. Pemetrexed 500 mg/m^2 and gemcitabine 1500 mg/m^2 will be given intravenously according to weight and height. All agents are administered every 2 weeks.
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: 48.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer

Summary:

      The primary objective is to determine the progression free survival with pemetrexed, and
      gemcitabine plus bevacizumab as first-line chemotherapy in elderly patients with Stage
      IIIB/IV non-small cell lung cancer (NSCLC).

      The secondary objectives are to determine the overall response rate; overall survival;
      chemotherapy induced toxicity profile of this combination; time to progression; and patient
      reported symptom burden.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient provides voluntary written informed consent before performance of any
             study-related procedure not part of normal medical care.

          -  Patient ≥ 65 years of age with ECOG of 0 to 1

          -  Patient must have histologically/cytologically confirmed Stage IIIB/IV NSCLC.

          -  Patient has measurable disease defined as at least 1 lesion that can be accurately
             measured in at least 1 dimension (by CT or MRI) & used to assess response as defined
             by RECIST criteria. Tumors within a previously irradiated field will be designated
             nontarget lesions.

          -  Patient has not received radiotherapy within 2 weeks(4 weeks required for brain
             metastases radiotherapy)of initial chemotherapy dosing for this study, and all acute
             toxicities due to prior radiotherapy have resolved prior to initial chemotherapy
             dosing.

          -  Patient has a negative serum pregnancy test or has undergone hysterectomy at time of
             enrollment.

          -  Greater than 12 weeks life expectancy.

          -  Patient has recovered from any recent surgery for at least 30 days & is free of active
             infection requiring antibiotics.

          -  Patient must be willing/able to discontinue use of NSAIDS prior to study drug dosing.

          -  Patient must be able to take folic acid, Vitamin B12, & dexamethasone per protocol.

          -  Patient must exhibit no greater than Grade 1 peripheral neuropathy.

        Exclusion Criteria:

          -  Prior systemic or other concurrent chemo for metastatic NSCLC(Prior Tarceva is not
             allowed).Prior adjuvant chemo acceptable as long as > 12 months since completion and
             no prior pemetrexed, gemcitabine or bevacizumab.

          -  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 acceptable.Patients with
             extrathoracic-only squamous cell NSCLC are eligible.Patients with only peripheral lung
             lesions (of any NSCLC histology) will also be eligible(a peripheral lesion is defined
             as a lesion in which the epicenter of the tumor is ≤ 2 cm from the costal or
             diaphragmatic pleura in a three-dimensional orientation based on each lobe of the lung
             and is > 2 cm from the trachea, main, and lobar bronchi).

          -  Hemoptysis within 1 month prior to study enrollment

          -  Ongoing treatment with full-dose warfarin or its equivalent i.e., unfractionated
             and/or low molecular weight heparin.(Low dose warfarin 1 mg given for prophylaxis is
             allowed).

          -  Hypersensitivity to any component of Alimta, gemcitabine &/or bevacizumab, &/or cannot
             tolerate folic acid, corticosteroids or Vitamin B12 supplements.

          -  Currently/have recently taken long-acting NSAID (Ibuprofen ≤ 400 mg QID acceptable) or
             aspirin (>325mg/day) within 5 days of initial pemetrexed administration.

          -  Clinically significant pericardial/pleural effusion or ascites unless able to be
             drained before study entry.

          -  Presence of third space fluid which cannot be controlled by drainage.

          -  Core biopsy/other minor surgical procedure(excluding placement of a vascular access
             device)within 7 days prior to study enrollment.

          -  Active infection or fever ≥ 38.5°C within 3 days of first scheduled day of protocol
             treatment.

          -  Serious, non-healing wound, ulcer, or untreated bone fracture.

          -  NYHA Grade II or greater CHF

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 &/or
             diastolic blood pressure > 100mmHg on antihypertensive meds)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy.

          -  History of MI, CVA, TIA, or unstable angina within 6 months of study enrollment.

          -  Significant vascular disease (aortic aneurysm, aortic dissection or recent peripheral
             arterial thrombosis.)

          -  Symptomatic peripheral vascular disease

          -  Known bleeding diathesis or coagulopathy

          -  Presence of CNS(central nervous system) except for treated brain metastases. 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.Anticonvulsants(stable dose)are allowed.Treatment for brain metastases may
             include whole brain radiotherapy(WBRT),radiosurgery(RS;Gamma Knife,LINAC,or
             equivalent)or a combination as deemed appropriate by the treating
             physician.Radiotherapy must be completed at least 4 weeks prior to study enrollment
             and all acute radiotherapy toxicities resolved.Patients with CNS metastases treated by
             neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will
             be excluded.

          -  A major surgical procedure, open biopsy, or significant traumatic injury within 28
             days prior to Day 1 or anticipation of need for major surgical procedure during the
             course of the study.

          -  Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6
             months prior to enrollment.

          -  History of prior malignancy within the past 5 years except for curatively treated
             basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized
             prostate cancer with a current prostate specific antigen of < 1.0 mg/dL on 2
             successive evaluations, at least 3 months apart, with the most recent evaluation no
             more than 4 weeks prior to entry.

          -  Have received radiotherapy to more than 25% of their bone marrow.

          -  Receiving concurrent investigational therapy or has received investigational therapy
             within 30 days of the first scheduled day of protocol treatment

          -  Pregnant/lactating.

          -  Any other medical condition deemed by the Investigator to be likely to interfere with
             a patient's ability to sign informed consent, cooperate/participate in the study, or
             interfere with interpretation of the results.

          -  History of allogeneic transplant.

          -  Known HIV infection or Hepatitis B or C.