Bevacizumab in Pats w/ Recurrent ST Brain Metas Who Have Failed Whole Brain Radiation Therapy
Condition: Metastatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Neoplasm Metastasis
Intervention: bevacizumab; quality-of-life assessment
Intervention description: Given IV; Ancillary studies
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study to evaluate a drug called bevacizumab in patients with cancer whose disease
      has spread to their brain. This study will not evaluate the effect of bevacizumab on the
      systemic solid tumor cancer. Bevacizumab is a medication and it is thought that bevacizumab
      may interfere with the growth of new blood vessels; therefore it might stop tumor growth and
      possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the
      blood vessels.
    

Eligibility criteria:

        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