Trial Outcomes & Findings for Bevacizumab in Pats w/ Recurrent ST Brain Metas Who Have Failed Whole Brain Radiation Therapy (NCT NCT01898130)

Last Updated: 2019-09-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

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

Results posted on

2019-09-17

Participant Flow

The study opened for accrual on October 11, 2013 with an accrual goal of up to 27 patients. The first patient started treatment November 27, 2013. The study was designed to enroll 9 patients initially and do an interim efficacy assessment. The study was closed permanently on April 24, 2017 with 27 patients enrolled.

Participant milestones

Participant milestones
Measure	Treatment (Bevacizumab) Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Treatment STARTED	27
Treatment Reached 1st Response/2 Cycles	24
Treatment Went on to Start Cycle 3	21
Treatment COMPLETED	21
Treatment NOT COMPLETED	6
Follow up Until PD or Death STARTED	27
Follow up Until PD or Death COMPLETED	26
Follow up Until PD or Death NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Bevacizumab) Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Treatment Withdrawal by Subject	2
Treatment Progressive Disease	4
Follow up Until PD or Death Lost to Follow-up	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Bevacizumab) n=27 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=24 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Objective Radiographic Tumor Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab	2 Participants

SECONDARY outcome

Timeframe: At 6 months from treatment initiation.

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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=24 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Progression-Free Survival (PFS) at 6 Months in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab	46 percentage of patients with PFS Interval 25.0 to 67.0

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=6 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Time to Progression in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab All Partial Response Patients	300 Days Interval 91.0 to 545.0
Time to Progression in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Clinical Partial Response	187 Days Interval 91.0 to 314.0
Time to Progression in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Radiological Partial Response	525 Days Interval 504.0 to 545.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=6 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Time to Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab All Partial Response Patients	73 Days Interval 53.0 to 116.0
Time to Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Clinical Partial Response	78 Days Interval 53.0 to 116.0
Time to Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Radiological Partial Response	62 Days Interval 55.0 to 69.0

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=6 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Duration of Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab All Partial Response Patients	227 Days Interval 11.0 to 490.0
Duration of Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Clinical Partial Response	110 Days Interval 11.0 to 119.0
Duration of Response in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Radiological Partial Response	463 Days Interval 435.0 to 490.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=27 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Overall Survival (OS) in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab	8.2 Months Interval 4.2 to 12.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=27 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Toxicity of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases Lymphocyte Count Decreased	1 participants
Toxicity of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases Headache	1 participants
Toxicity of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases Hypertension	3 participants
Toxicity of Bevacizumab in Patients With Recurrent Solid Tumor Brain Metastases Thromboembolic Event	1 participants

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=12 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Baseline FACT-G	83.0 score on a scale Interval 67.7 to 105.0
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Baseline BrCS	64.8 score on a scale Interval 46.0 to 87.0
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Baseline TOTAL	147.8 score on a scale Interval 124.3 to 189.0
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Baseline TOI	106.0 score on a scale Interval 77.0 to 139.0
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Cycle 3 FACT-G	75.9 score on a scale Interval 50.8 to 99.0
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Cycle 3 BrCS	62.8 score on a scale Interval 36.1 to 80.0
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Cycle 3 TOTAL	138.7 score on a scale Interval 93.8 to 178.0
Quality of Life Assessments in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab Cycle 3 TOI	99.4 score on a scale Interval 57.1 to 130.0

POST_HOC outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=24 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Response Rate in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab	6 Participants

POST_HOC outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Treatment (Bevacizumab) n=27 Participants Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Progression Free Survival (PFS) in Patients With Recurrent Solid Tumor Brain Metastases Treated With Bevacizumab	4.3 Months Interval 3.3 to 7.7

Adverse Events

Treatment (Bevacizumab)

Serious events: 19 serious events

Other events: 27 other events

Deaths: 24 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Bevacizumab) n=27 participants at risk Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clinical Decline	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Headache	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease Progression	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Blood and lymphatic system disorders Febrile Neutropenia	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Infections and infestations Viral Gastroenteritis	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Transient Ischemic Attack	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Death due to Intracranial Hemorrhage	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Infections and infestations Pneumonia	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Infections and infestations Viral Illness	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Vomiting	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
General disorders Death NOS (Not otherwise specified)	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Seizure	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Dysarthria	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Colitis	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Blood Bilirubin Increased	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Respiratory, thoracic and mediastinal disorders Dyspnea	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Radiation Enteritis	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Constipation	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Respiratory, thoracic and mediastinal disorders Pulmonary Edema	3.7% 1/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.

Other adverse events

Other adverse events
Measure	Treatment (Bevacizumab) n=27 participants at risk Patients receive 10mg/kg bevacizumab IV over 30-90 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Quality-of-life assessment: Ancillary studies
Blood and lymphatic system disorders Anemia	51.9% 14/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Ear and labyrinth disorders Tinnitus	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Eye disorders Blurred Vision	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Constipation	29.6% 8/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Diarrhea	14.8% 4/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Nausea	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Gastrointestinal disorders Vomiting	18.5% 5/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
General disorders Edema Limbs	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
General disorders Fatigue	48.1% 13/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
General disorders Fever	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
General disorders Gait Disturbance	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
General disorders Pain	14.8% 4/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Infections and infestations Sinusitis	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Infections and infestations Urinary Tract Infection	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Injury, poisoning and procedural complications Fall	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Activated Partial Thromboplastin Time Prolonged	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Alanine Aminotransferase Increased	22.2% 6/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Alkaline Phosphatase Increased	29.6% 8/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Aspartate Aminotransferase Increased	48.1% 13/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Blood Bilirubin Increased	22.2% 6/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Lymphocyte Count Decreased	74.1% 20/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Neutrophil Count Decreased	18.5% 5/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Platelet Count Decreased	29.6% 8/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Weight Gain	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations Weight Loss	29.6% 8/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Investigations White Blood Cell Decreased	40.7% 11/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Metabolism and nutrition disorders Anorexia	18.5% 5/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Metabolism and nutrition disorders Hyperglycemia	74.1% 20/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Metabolism and nutrition disorders Hypoalbuminemia	77.8% 21/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Metabolism and nutrition disorders Hypocalcemia	44.4% 12/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Metabolism and nutrition disorders Hypoglycemia	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Metabolism and nutrition disorders Hypokalemia	44.4% 12/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Metabolism and nutrition disorders Hyponatremia	70.4% 19/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Musculoskeletal and connective tissue disorders Back Pain	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Amnesia	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Dizziness	14.8% 4/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Dysarthria	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Dysphasia	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Headaches	22.2% 6/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Memory Impairment	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Peripheral Motor Neuropathy	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Paresthesia	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Nervous system disorders Delirium	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Renal and urinary disorders Hematuria	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Renal and urinary disorders Urinary Incontinence	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Renal and urinary disorders Urinary Frequency	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Renal and urinary disorders Proteinuria	14.8% 4/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Respiratory, thoracic and mediastinal disorders Cough	18.5% 5/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Respiratory, thoracic and mediastinal disorders Epistaxis	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Respiratory, thoracic and mediastinal disorders Hoarseness	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	11.1% 3/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Skin and subcutaneous tissue disorders Alopecia	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Skin and subcutaneous tissue disorders Palmar-Planar Erythrodysesthesia Syndrome	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Skin and subcutaneous tissue disorders Pruritus	7.4% 2/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.
Vascular disorders Hypertension	59.3% 16/27 • Adverse Events were collected from the start of treatment, through 30 days post last treatment with patients being treated twice (every 14 days) in a 28 day cycle. Range of cycles completed 1-20.

Additional Information

Priya Kumthekar, MD

Northwestern University

Phone: 312-503-1818

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place