A Phase II Study of Pemetrexed and Gemcitabine Plus Bevacizumab as First Line Chemotherapy for Elderly Patients With Stage IIIB/IV Non-Small Cell Lung Cancer
- 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
- 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
- Patient has a negative serum pregnancy test or has undergone hysterectomy at time of
- 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.
- 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
- 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
- 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
- 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
- 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.