Bevacizumab in Pats w/ Recurrent ST Brain Metas Who Have Failed Whole Brain Radiation Therapy

PRIMARY OBJECTIVES:

I. Determine the radiographic response rate in patients with solid tumor brain metastases
treated with bevacizumab.

SECONDARY OBJECTIVES:

I. Estimate the progression-free survival (PFS) rate at 6 months. II. Determine the time to
progression based on magnetic resonance imaging (MRI) or computed tomography (CT) scans.

III. Determine the time to response based on radiographic imaging. IV. Determine the duration
of response based on radiographic imaging. V. Determine overall survival. VI. Collect
additional safety data. VII. Assess changes in quality of life using the Functional
Assessment of Cancer Therapy-Brain (FACT-Br) while on treatment.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes every 2 weeks. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks.

Inclusion Criteria:

- Patients must have a histologically or cytologically confirmed non-central nervous
system (CNS) primary solid malignancy at the time of initial diagnosis; NOTE: brain
lesions are not required to have pathologic confirmation; in addition, a copy of the
pathology report for the primary tumor is sufficient for registration purposes

- Patients must have radiographically-confirmed recurrent brain metastases from a solid
tumor after WBRT

- Patients must have measurable or evaluable disease in the brain

- Patients must have been on a stable dose of corticosteroids >= 5 days prior to
obtaining their baseline gadolinium (Gd)-MRI of brain

- Patients must have completed WBRT > 12 weeks prior to enrollment to limit cases of
pseudoprogression; however if new lesions are noted < 12 weeks but > 4 weeks prior to
enrollment, those patients are eligible

- Patients who underwent radiosurgery to treat a progressive lesion must have
confirmation of tumor by tissue, magnetic resonance spectroscopy (MRS), magnetic
resonance (MR) perfusion or positron emission tomography (PET) and the lesion must be
measurable; NOTE: radiosurgery may be done to a lesion that will not be used for
response evaluation and should be done > 2 weeks prior to enrollment

- Patients may be on other systemic chemotherapies if progressive CNS disease occurs
while on these treatments; NOTE: new systemic chemotherapies should not be started
unless required to treat systemic disease and should not start until at least 1 follow
up imaging study has been performed

- Patients may have received any number of prior CNS directed therapies - there are no
limitations

- Patients must have a life expectancy of >= 12 weeks

- Patients must have a Karnofsky performance score (KPS) of >= 60

- Whole blood cell (WBC) >= 3,000/ul

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelets >= 100,000/mm^3

- Hemoglobin >= 10 gm/dl (may be reached by transfusion)

- Serum glutamic oxaloacetic transaminase (SGOT) < 2 x upper limit of normal (ULN) (or <
5 x ULN if liver is involved)

- Bilirubin < 2 x ULN (or < 5 x ULN if liver is involved)

- Creatinine < 1.5 x ULN

- Patients of both sexes must agree to the use of barrier contraceptives throughout the
duration of treatment on this trial and for 3 months after discontinuing treatment;
NOTE: hormonal contraceptives are not acceptable as a sole method of contraception

- Patients must be > 4 weeks from any major surgery

- Patients NOT on warfarin must have a prothrombin time (PT)/international normalized
ratio (INR) < 1.4 within 14 days prior to registration

- Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight
[LMW] heparin) must meet BOTH of the following criteria within 14 days prior to
registration:

- No active bleeding or pathological condition that carries a high risk of
bleeding (e.g., tumor involving major vessels or known varices)

- In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on
a stable dose of LMW heparin

- Female patients of child-bearing potential must have a negative pregnancy test within
14 days prior to registration

- Patients must be willing and able to comply with study and/or follow-up procedures

- Patients must sign an informed consent prior to registration and before undergoing any
study-specific procedures indicating that they are aware of the investigational nature
of this study

Exclusion Criteria:

- Patients with a diagnosis of intrathoracic lung carcinoma of squamous cell histology
are not eligible for participation

- Female patients who are pregnant or breast feeding, or adults of reproductive
potential who are not using barrier birth control methods, are not eligible for
participation

- Patients must not have baseline proteinuria within 14 days prior to registration as
demonstrated by either:

- Urine protein: creatinine (UPC) ratio < 1.0 at screening, OR

- Urine dipstick for proteinuria =< 2+; NOTE: patients discovered to have >= 2+
proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine
collection and must demonstrate =< 1g of protein in 24 hours to be eligible

- Patients must not have experienced any major surgical procedure, open biopsy, or
significant traumatic injury within 28 days prior to registration, or be anticipated
to need a major surgical procedure during the course of the study; NOTE: the exception
is craniotomy

- Patients must not have experienced a core biopsy or other minor surgical procedure
within 7 days prior to registration; NOTE: this excludes placement of a vascular
access device

- Patients with a history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within the previous 6 months are not eligible for
participation

- Patients with a serious, non-healing wound, ulcer, or bone fracture are not eligible
for participation due to the effects on vasculature by bevacizumab which may impair
healing

- Patients known to be human immunodeficiency virus (HIV) or hepatitis B and/or C
positive are not eligible for participation; NOTE: HIV and hepatitis testing is not
required for study participation

- Patients with a history of any other cancer (except for non-melanoma skin cancer or
carcinoma in-situ of the cervix), are not eligible for participation unless they are
in complete remission and have been off of all therapy for that disease for a minimum
of 3 years

- Patients receiving or participating on any other experimental agents/clinical trials
are not eligible for participation

- Patients with a known hypersensitivity to any component of bevacizumab are not
eligible for participation

- Patients with any significant medical illnesses or infection that, in the
investigator's opinion, cannot be adequately controlled with appropriate therapy or
would compromise the patient's ability to tolerate this therapy are not eligible for
participation

- Patients with leptomeningeal disease are not eligible for participation

- Patients who have received previous treatment with bevacizumab for CNS disease are not
eligible for participation

- Patients with inadequately controlled hypertension (defined as systolic blood pressure
> 150 and/or diastolic blood pressure > 100 mmHg) are not eligible for participation