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

Radiographic Response to treatment will be assessed prior to every odd-numbered cycle using CT or MRI scans until disease progression, unacceptable toxicity as assessed by the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Response is defined as the number of patients with Complete Response (CR) plus those with Partial Response (PR) radiographically. Generally CR is defined as the disappearance of all target lesions and PR is defined as \>=50% decrease in the sum of the longest diameter of target lesions.

Time frame: Every other cycle, starting cycle 3 (1 cycle =28 days) until off study. Range of cycles completed 1-20.

Population: Not all patients treated on study were determined to be evaluable for this objective as they did not receive follow up scans after the baseline scans.

The Duration of Overall Response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) until the first date that recurrent or Progressive Disease (PD) is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Duration of response will be based on CT or MRI scans and clinical assessment performed prior to every odd-numbered cycle to detect date of first response to study treatment until date of disease progression and assessed by the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Generally CR is defined as the disappearance of all target lesions, PR is defined as \>=50% decrease in the sum of the longest diameter of target lesions and PD is defined as a 25% or more increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame: From documentation of response, every two cycles (1 cycle =28 days) until progressive disease. Range of cycles completed 1-20.

Population: Patients that achieved documented Complete Response or Partial Response were evaluated for this outcome measure

Overall Survival (OS) will be measured as the date of first dose of bevacizumab to the date of death from any cause. To estimate OS, Kaplan-Meier curves will be calculated and OS will be determined from the overall survival curve.

Time frame: From start of treatment until death from any cause. Median follow up of 8 months (range 1.3 to 47.9 months)

Population: All patients included in OS outcome measure.

Progression-Free Survival (PFS) will be measured as the time from the first dose to the first occurrence of progression or death for any reason. To estimate PFS, Kaplan-Meier curves will be calculated and PFS at 6 months will be determined from the progression-free survival curve. Progression is defined using Response Assessment in Neuro-Oncology Criteria (RANO), as a 25% or more increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame: At 6 months from treatment initiation.

Changes in quality of life will be evaluated using questionnaires (FACT-Br) at baseline (before treatment initiation) and at cycle 3. Four FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient. FACT-G (Fact General, possible range 0 - 108) BrCS (Brain Cancer Subscale, possible range 0 - 92) TOTAL (FACT-G + BrCS, possible range 0 - 200) TOI (Trial Outcome Index = Physical Well Being \_ Functional Well Being +BrCS, possible range 0 - 148)

Time frame: Baseline and at Cycle 3 (1 Cycle = 28 days).

Population: 12 patients completed quality of life questionnaires at baseline and Cycle 3 and therefore are evaluable for this outcome measure.

MRI or CT scans and clinical assessment will be used to measure Time to Progression which will be assessed as the time from the date of first dose to the date of first observation of progressive disease, non-reversible neurologic progression or increasing steroid requirements, or early discontinuation of treatment as assessed by the RANO Criteria in those patients that experience response.

Time frame: From treatment initiation, every 2 cycles (1 cycle = 28 days) until progressive disease. Range of cycles completed 1-20.

Population: 6 patients experienced response and were evaluable for this outcome measure

MRI or CT scans and clinical assessment will be used to measure Time to Response which will be assessed as the time from the date of first dose to the date of first observed tumor response in all patients that a response is observed. Response to treatment will be assessed using the Response Assessment in Neuro-Oncology (RANO) Criteria for target lesions. Response is defined as either Complete Response (CR) or a Partial Response (PR) radiographically. Generally CR is defined as the disappearance of all target lesions and PR is defined as \>=50% decrease in the sum of the longest diameter of target lesions.

Time frame: From the start of treatment every 2 cycles (1 cycle =28 days) until time of response. Range of cycles completed 1-20.

Population: 6 patients experienced a response and were therefore evaluable for this outcome measure.

Adverse events (AE) will be collected at the start of every cycle and graded according NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All AEs that are determined to be grade 3 or higher and at least possible related to bevacizumab will be reported for toxicity. In general AEs will be graded: Grade 1 - Mild: the event causes discomfort without disruption of normal daily activities. Grade 2 - Moderate: the event causes discomfort that affects normal daily activities. Grade 3 - Severe: the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Grade 4 - Life-threatening: the patient was at risk of death at the time of the event. Grade 5 - Fatal: the event caused death.

Time frame: Assessed prior to every cylcle (cycle=28 days) while on treatment through 30 days post last dose. Range of cycles 1-20.

Population: All patients that receive at least one dose of bevacizumab are considered to be evaluable for toxicity outcome measure.

Progression Free Survival (PFS) is measured from the time of treatment initiation until documentation of progressive disease or death from any cause. To estimate PFS, Kaplan-Meier curves will be calculated and PFS will be determined from the progression-free survival curve. Progression is defined using Response Assessment in Neuro-Oncology Criteria (RANO), as a 25% or more increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time frame: From treatment initiation and every two cycles (1 cycle = 28 days) until disease progression. Median follow up of 8 months (range 1.3 to 47.9 months).

Population: All patients evaluable for this outcome measure.

Response Rate is defined as all patients with Complete Response plus those with Partial Response as assessed by Response Assessment in Neuro-Oncology (RANO) Criteria of CT or MRI scans for target lesions combined with clinical assessment. Generally RANO Response definitions are as follows: CR is defined as the disappearance of all target lesions and PR is defined as \>=50% decrease in the sum of the longest diameter of target lesions.

Time frame: Every other cycle, starting cycle 3 (1 cycle =28 days) until off study. Range of cycles completed 1-20.

Population: 3 patients were determined not to be evaluable for response outcome measures as they did not get follow up scans after baseline scans.