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Intrathecal Trastuzumab for Leptomeningeal Metastases in HER2+ Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01325207
Recruitment Status : Completed
First Posted : March 29, 2011
Results First Posted : May 28, 2019
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
Northwestern University

Study Type Interventional
Study Design Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Intervention Radiation: Trastuzumab
Enrollment 34
Recruitment Details The study opened for accrual on April 26, 2011 with first patient being treated August 1, 2011, with an accrual goal of up to 48 patients for phase I/II combined. Amendment 5 added 5th cohort to allow higher dose. The study was suspended April 12, 2014 and reopened on August 28, 2014 for phase II. The study closed to accrual June 2, 2016.
Pre-assignment Details  
Arm/Group Title Cohort 1 - Trastuzumab 10mg IT 2/Week Cohort 2 - Trastuzumab 20mg IT 2/Week Cohort 3- Trastuzumab 40mg IT 2/Week Cohort 4 - Trastuzumab 60mg IT 2/Week Cohort 5 - 80mg IT 2/Week Phase II - Transtuzumab 80mg IT 2/Week
Hide Arm/Group Description

Intrathecal Trastuzumab 10 mg IT will be administered in Cohort 1 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 20 mg IT will be administered in Cohort 2 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 40 mg IT will be administered in Cohort 3 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 60 mg IT will be administered in Cohort 4 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 80 mg IT will be administered in Cohort 5 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 10 mg IT will be administered in phase II portion of the study.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Period Title: Completed 4 Weeks/1 Cycle of Treatment
Started 3 3 1 1 7 19
Completed 3 3 1 1 5 19
Not Completed 0 0 0 0 2 0
Reason Not Completed
Adverse Event             0             0             0             0             2             0
Period Title: Completed 8 Weeks/2 Cycles of Treatment
Started 3 3 1 1 5 19
Completed 2 2 1 1 3 14
Not Completed 1 1 0 0 2 5
Reason Not Completed
Progressive Disease             1             1             0             0             2             5
Period Title: Started 9th Week/Cycle 3 of Treatment
Started 2 2 1 1 3 14
Completed 1 0 0 0 3 9
Not Completed 1 2 1 1 0 5
Reason Not Completed
Progressive disease             1             1             1             1             0             4
Withdrawal by Subject             0             1             0             0             0             0
Adverse Event             0             0             0             0             0             1
Period Title: Follow-up Every 3 Months Until Death
Started [1] 3 3 1 1 7 19
Completed 3 3 1 1 6 18
Not Completed 0 0 0 0 1 1
Reason Not Completed
Lost to Follow-up             0             0             0             0             0             1
Follow-up Considered Complete             0             0             0             0             1             0
[1]
All patients treated on study went into the follow up period.
Arm/Group Title Cohort 1 - Trastuzumab 10mg IT 2/Week Cohort 2 - Trastuzumab 20mg IT 2/Week Cohort 3- Trastuzumab 40mg IT 2/Week Cohort 4 - Trastuzumab 60mg IT 2/Week Cohort 5 - 80mg IT 2/Week Phase II - Transtuzumab 80mg IT 2/Week Total
Hide Arm/Group Description

Intrathecal Trastuzumab 10 mg IT will be administered in Cohort 1 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 20 mg IT will be administered in Cohort 2 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 40 mg IT will be administered in Cohort 3 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 60 mg IT will be administered in Cohort 4 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 80 mg IT will be administered in Cohort 5 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 10 mg IT will be administered in phase II portion of the study.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Total of all reporting groups
Overall Number of Baseline Participants 3 3 1 1 7 19 34
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 1 participants 1 participants 7 participants 19 participants 34 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
 100.0%
3
 100.0%
1
 100.0%
1
 100.0%
6
  85.7%
17
  89.5%
31
  91.2%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
2
  10.5%
3
   8.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 1 participants 1 participants 7 participants 19 participants 34 participants
Female
2
  66.7%
3
 100.0%
1
 100.0%
1
 100.0%
7
 100.0%
18
  94.7%
32
  94.1%
Male
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
2
   5.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 1 participants 1 participants 7 participants 19 participants 34 participants
Hispanic or Latino
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
2
   5.9%
Not Hispanic or Latino
2
  66.7%
3
 100.0%
1
 100.0%
1
 100.0%
7
 100.0%
18
  94.7%
32
  94.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 1 participants 1 participants 7 participants 19 participants 34 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
1
   2.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
  15.8%
3
   8.8%
White
3
 100.0%
3
 100.0%
1
 100.0%
1
 100.0%
7
 100.0%
14
  73.7%
29
  85.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.3%
1
   2.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 1 participants 1 participants 7 participants 19 participants 34 participants
3
 100.0%
3
 100.0%
1
 100.0%
1
 100.0%
7
 100.0%
19
 100.0%
34
 100.0%
1.Primary Outcome
Title Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Hide Description

Patients will be treated using a standard 3+3 dose-escalation design for cohorts 1 and 2. This will be followed by an accelerated phase I for cohorts 3 and 4, and then a standard 3 + 3 for the 5th cohort. In the accelerated phase (cohorts 3 and 4), 1 patient will be enrolled per cohort; if a toxicity is seen in that patient then the cohort would be expanded to 6 patients to allow for 1/6 patients per cohort to have a dose limiting toxicity (DLT) before dose escalation. Cohort 5 will enroll a total of 6 patients regardless of the toxicity experienced in patient one. However, if 2 or more DLTs are observed in cohort 5, cohort 4 will be reopened to enroll of a total of 6 patients. Whatever dose is ultimately declared the MTD should have 6 patients total. If 1/6 DLTs are seen in cohort 5 that will be considered the MTD.

Dosing is as follows:

Cohort 1-10 mg IT Cohort 2-20 mg IT Cohort 3-40 mg IT Cohort 4-60 mg IT Cohort 5-80 mg IT

Time Frame From treatment initiation through the first 4 weeks of treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - Trastuzumab 10mg IT 2/Week Cohort 2 - Trastuzumab 20mg IT 2/Week Cohort 3- Trastuzumab 40mg IT 2/Week Cohort 4 - Trastuzumab 60mg IT 2/Week Cohort 5 - 80mg IT 2/Week
Hide Arm/Group Description:

Intrathecal Trastuzumab 10 mg IT will be administered in Cohort 1 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 20 mg IT will be administered in Cohort 2 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 40 mg IT will be administered in Cohort 3 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 60 mg IT will be administered in Cohort 4 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 80 mg IT will be administered in Cohort 5 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Overall Number of Participants Analyzed 3 3 1 1 7
Measure Type: Number
Unit of Measure: DLTs
0 0 0 0 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1 - Trastuzumab 10mg IT 2/Week, Cohort 2 - Trastuzumab 20mg IT 2/Week, Cohort 3- Trastuzumab 40mg IT 2/Week, Cohort 4 - Trastuzumab 60mg IT 2/Week, Cohort 5 - 80mg IT 2/Week
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Other Statistical Analysis The Maximum Tolerated Dose (MTD) was determined to be 80mg IT every two weeks. This is based on no DLTs being seeing in Cohorts 1-4 with lower doses and 1 DLT out of 7 patients observed at 80mg IT in Cohort 5.
2.Primary Outcome
Title Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Hide Description Best response will be assessed using a combination CSF cytology assessment, radiographic assessment and clinical function assessments. Best response will be defined as the best response seen during treatment as compared to baseline that is confirmed on subsequent response assessment.
Time Frame Baseline then at 4 weeks, 8 weeks and then every 8 weeks +/- 3 days, until disease progression or toxicity,range of cycles completed 1-22 cycles where 1 cycle = 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients were assessed for response. Patients unable to be assessed were determined to have progressive disease and counted. Cohort results for this outcome measure were analysed combined and at the MTD of 80mg IT (Cohort 5 + phase II). The objective was to determine preliminary response data for this treatment combination.
Arm/Group Title Treatment With Trastuzumab Cohort 5 + Phase II - Intrathecal Trastuzumab- 80 mg
Hide Arm/Group Description:

Intrathecal Trastuzumab will be administered in a dose escalation design from 10mg up to 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Intrathecal Trastuzumab will be administered at the MTD determined dose of 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Overall Number of Participants Analyzed 34 26
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
0
   0.0%
Partial Response
6
  17.6%
5
  19.2%
Stable Disease
18
  52.9%
13
  50.0%
Progressive Disease
10
  29.4%
8
  30.8%
3.Other Pre-specified Outcome
Title Define the CSF PK of IT Trastuzumab.
Hide Description Patients may need a CSF flow study at the discretion of the treating principal investigator. If a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment. Concurrent radiation is not allowed.
Time Frame CSF analysis for cytology will be done every 2 weeks when CSF is obtained for PK and then every 4 weeks
Outcome Measure Data Not Reported
4.Post-Hoc Outcome
Title Progression Free Survival (PRS) at 6 Months and at 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Hide Description Progression Free Survival (PFS) will be measured from the time of treatment initiation until the first documentation of progression. To estimate the probability of PFS at 6 months and 12 months, Kaplan-Meier curves will be calculated and PFS at 6 months and 12 months will be determined from the progression-free survival curve. Progression will be defined as worsening clinical signs or development of new clinical symptoms that the Investigator feels can be attributed to Leptomeningeal disease.
Time Frame At 6 and 12 months from start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on PFS of patients with this drug combination.
Arm/Group Title Treatment With Trastuzumab Cohort 5 + Phase II - Intrathecal Trastuzumab- 80 mg
Hide Arm/Group Description:

Intrathecal Trastuzumab will be administered in a dose escalation design from 10mg up to 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Intrathecal Trastuzumab will be administered at the MTD determined dose of 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Overall Number of Participants Analyzed 34 26
Measure Type: Number
Unit of Measure: Probability of Survival
PFS at 6 months 0.235 0.269
PFS at 12 months 0.118 0.115
5.Post-Hoc Outcome
Title Overall Survival (OS) at 6 and 12 Months in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Hide Description Overall Survival (OS) will be measured from the time of treatment initiation until death from any cause. To estimate OS probability at 6 and 12 months, Kaplan-Meier curves will be calculated and OS at 612 months will be determined from the overall survival curve.
Time Frame At 6 and 12 months from start of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on OS of patients with this drug combination.
Arm/Group Title Treatment With Trastuzumab Cohort 5 + Phase II - Intrathecal Trastuzumab- 80 mg
Hide Arm/Group Description:

Intrathecal Trastuzumab will be administered in a dose escalation design from 10mg up to 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Intrathecal Trastuzumab will be administered at the MTD determined dose of 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Overall Number of Participants Analyzed 34 26
Measure Type: Number
Unit of Measure: Probability of Survival
OS at 6 months 0.562 0.542
OS at 12 months 0.406 0.458
6.Post-Hoc Outcome
Title Median Progression Free Survival (PFS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Hide Description Progression Free Survival (PFS) will be measured from the time of treatment initiation until the first documentation of progression. To estimate PFS, Kaplan-Meier curves will be calculated and the median PFS will be determined from the progression-free survival curve. Progression will be defined as worsening clinical signs or development of new clinical symptoms that the Investigator feels can be attributed to Leptomeningeal disease.
Time Frame From start of treatment, and during treatment until progressive disease for up to 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on PFS of patients with this drug combination
Arm/Group Title Treatment With Trastuzumab Cohort 5 + Phase II - Intrathecal Trastuzumab- 80 mg
Hide Arm/Group Description:

Intrathecal Trastuzumab will be administered in a dose escalation design from 10mg up to 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Intrathecal Trastuzumab will be administered at the MTD determined dose of 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Overall Number of Participants Analyzed 34 26
Median (95% Confidence Interval)
Unit of Measure: Months
1.885
(1.541 to 3.738)
2.148
(1.016 to 7.344)
7.Post-Hoc Outcome
Title Median Overall Survival (OS) in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer.
Hide Description Overall Survival (OS) will be measured from start of treatment until death from any cause. To estimate OS, Kaplan-Meier curves will be calculated and median OS will be determined from the progression-free survival curve.
Time Frame From start of treatment until death from any cause for up to 60 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Cohort results for this outcome measure were analyzed both combined and for patients treated at the MTD dose of 80mg IT as the objective was to determine preliminary data on OS of patients with this drug combination
Arm/Group Title Treatment With Trastuzumab Cohort 5 + Phase II - Intrathecal Trastuzumab- 80 mg
Hide Arm/Group Description:

Intrathecal Trastuzumab will be administered in a dose escalation design from 10mg up to 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Intrathecal Trastuzumab will be administered at the MTD determined dose of 80 mg IT.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks.

1 cycle = 28 days

Overall Number of Participants Analyzed 34 26
Median (95% Confidence Interval)
Unit of Measure: percentage of patients
8.738
(5.607 to 17.311)
8.328
(5.148 to 19.541)
Time Frame Adverse events were collected over a 6 year period for the study. Patients were followed from first day of treatment until 30 days post first treatment for a maximum of 22 cycles (longest time any patient received treatment) where 1 cycle = 28 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 - Trastuzumab 10mg IT 2/Week Cohort 2 - Trastuzumab 20mg IT 2/Week Cohort 3- Trastuzumab 40mg IT 2/Week Cohort 4 - Trastuzumab 60mg IT 2/Week Cohort 5 - 80mg IT 2/Week Phase II - Transtuzumab 80mg IT 2/Week
Hide Arm/Group Description

Intrathecal Trastuzumab 10 mg IT will be administered in Cohort 1 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 20 mg IT will be administered in Cohort 2 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 40 mg IT will be administered in Cohort 3 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 60 mg IT will be administered in Cohort 4 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 80 mg IT will be administered in Cohort 5 of dose escalation.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

Intrathecal Trastuzumab 10 mg IT will be administered in phase II portion of the study.

Trastuzumab: Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks until disease progression or unacceptable toxicity.

1 cycle = 28 days.

All-Cause Mortality
Cohort 1 - Trastuzumab 10mg IT 2/Week Cohort 2 - Trastuzumab 20mg IT 2/Week Cohort 3- Trastuzumab 40mg IT 2/Week Cohort 4 - Trastuzumab 60mg IT 2/Week Cohort 5 - 80mg IT 2/Week Phase II - Transtuzumab 80mg IT 2/Week
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)      3/3 (100.00%)      1/1 (100.00%)      1/1 (100.00%)      5/7 (71.43%)      17/19 (89.47%)    
Hide Serious Adverse Events
Cohort 1 - Trastuzumab 10mg IT 2/Week Cohort 2 - Trastuzumab 20mg IT 2/Week Cohort 3- Trastuzumab 40mg IT 2/Week Cohort 4 - Trastuzumab 60mg IT 2/Week Cohort 5 - 80mg IT 2/Week Phase II - Transtuzumab 80mg IT 2/Week
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/3 (33.33%)      2/3 (66.67%)      1/1 (100.00%)      1/1 (100.00%)      3/7 (42.86%)      13/19 (68.42%)    
Cardiac disorders             
Pericardial effusion  1 [1]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders             
Abdominal muscle wall hemorrhage  1 [2]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Dehydration  1 [3]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  2
Gastroenteritis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  2
Dehydration  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Vomiting  1 [4]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Colonic perforation  1 [5]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Abdominal pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Infections and infestations             
Chemical meningitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 2/19 (10.53%)  2
Lung infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/7 (14.29%)  1 0/19 (0.00%)  0
Wound infection  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 0/19 (0.00%)  0
Enterocolitis infectious  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0 0/7 (0.00%)  0 0/19 (0.00%)  0
Metabolism and nutrition disorders             
Hyponatremia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  2
Musculoskeletal and connective tissue disorders             
Pain in back and extremities  1 [6]  0/3 (0.00%)  0 0/3 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0 0/7 (0.00%)  0 0/19 (0.00%)  0
Muscle weakness  1 [7]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 1/1 (100.00%)  1 0/7 (0.00%)  0 0/19 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Death due to progressive disease  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Clinical deterioration  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 0/19 (0.00%)  0
Nervous system disorders             
Dysphasia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Seizure  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 2/19 (10.53%)  2
Worsening Mental Status  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Syncope  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Vasivagal reaction  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Worsening neurological symptoms  1  0/3 (0.00%)  0 2/3 (66.67%)  2 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 0/19 (0.00%)  0
Hydrocephalus  1 [8]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/7 (14.29%)  1 0/19 (0.00%)  0
Arachnoiditis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 1/7 (14.29%)  1 0/19 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Death due to aspiration pneumonia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Esophagitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
Vascular disorders             
Thromboembolic event (DVT)  1 [9]  0/3 (0.00%)  0 0/3 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/7 (0.00%)  0 1/19 (5.26%)  1
1
Term from vocabulary, CTCAE (4.03)
Indicates events were collected by systematic assessment
[1]
Patient also experienced venous thromboembolism during inpatient hospitalization.
[2]
Patient experienced abdominal pain during this event.
[3]
Patients experienced generalized weakness and abdominal pain during the inpatient hospitalization.
[4]
Patient experienced nausea during this inpatient hospitalization.
[5]
Patient also experienced confusion during this inpatient hospitalization.
[6]
Patient also experienced Nausea and headache during this inpatient hospitalization
[7]
Patient also experienced gait disturbance during this hospitalization.
[8]
Patient also experienced somnolence during this hospitalization.
[9]
Patient also experienced pulmonary embolism during this inpatient hospitalization.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 - Trastuzumab 10mg IT 2/Week Cohort 2 - Trastuzumab 20mg IT 2/Week Cohort 3- Trastuzumab 40mg IT 2/Week Cohort 4 - Trastuzumab 60mg IT 2/Week Cohort 5 - 80mg IT 2/Week Phase II - Transtuzumab 80mg IT 2/Week
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      3/3 (100.00%)      1/1 (100.00%)      1/1 (100.00%)      7/7 (100.00%)      19/19 (100.00%)    
Blood and lymphatic system disorders             
Anemia  1  2/3 (66.67%)  2/3 (66.67%)  0/1 (0.00%)  0/1 (0.00%)  4/7 (57.14%)  9/19 (47.37%) 
Febrile neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Cardiac disorders             
Palpitations  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Ear and labyrinth disorders             
Hearing impaired  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Tinnitus  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Eye disorders             
Blurred vision  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Gastrointestinal disorders             
Abdominal pain  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Constipation  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  2/19 (10.53%) 
Diarrhea  1  1/3 (33.33%)  2/3 (66.67%)  1/1 (100.00%)  0/1 (0.00%)  1/7 (14.29%)  2/19 (10.53%) 
Dry mouth  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Dysphagia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Fecal incontinence  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Hemorrhoids  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  2/19 (10.53%) 
Mucositis oral  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Nausea  1  1/3 (33.33%)  2/3 (66.67%)  0/1 (0.00%)  1/1 (100.00%)  3/7 (42.86%)  2/19 (10.53%) 
Upper gastrointestinal hemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Vomiting  1  0/3 (0.00%)  2/3 (66.67%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  3/19 (15.79%) 
Decreased appetite  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Chills  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
General disorders             
Edema in limbs  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Edema in head  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Fatigue  1  0/3 (0.00%)  0/3 (0.00%)  1/1 (100.00%)  0/1 (0.00%)  3/7 (42.86%)  4/19 (21.05%) 
Fever  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Flu like symptoms  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Gait disturbance  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  1/1 (100.00%)  0/7 (0.00%)  2/19 (10.53%) 
Non-cardiac Chest Pain  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Pain  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  1/1 (100.00%)  0/7 (0.00%)  2/19 (10.53%) 
Infections and infestations             
Lung infection  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Paronychia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Skin infection  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Urinary tract infection  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Vaginal infection  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Injury, poisoning and procedural complications             
Fall  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  2/19 (10.53%) 
Dermatitis radiation  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Investigations             
Activated Partial Thromboplastin Time Prolonged  1  0/3 (0.00%)  1/3 (33.33%)  1/1 (100.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Alanine Aminotransferase Increased  1  0/3 (0.00%)  1/3 (33.33%)  1/1 (100.00%)  1/1 (100.00%)  2/7 (28.57%)  5/19 (26.32%) 
Alkaline Phosphatase Increased  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  1/1 (100.00%)  1/7 (14.29%)  3/19 (15.79%) 
Aspartate Aminotransferase Increased  1  0/3 (0.00%)  0/3 (0.00%)  1/1 (100.00%)  1/1 (100.00%)  3/7 (42.86%)  3/19 (15.79%) 
Blood Antidiuretic Hormone Abnormal  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Blood Bilirubin Increased  1  0/3 (0.00%)  0/3 (0.00%)  1/1 (100.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Lymphocyte Count Decreased  1  2/3 (66.67%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  8/19 (42.11%) 
Neutrophil Count Decreased  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Platelet Count Decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/1 (100.00%)  1/1 (100.00%)  1/7 (14.29%)  5/19 (26.32%) 
White Blood Cell Decreased  1  1/3 (33.33%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  6/19 (31.58%) 
Metabolism and nutrition disorders             
Dehydration  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  2/19 (10.53%) 
Hyperglycemia  1  2/3 (66.67%)  2/3 (66.67%)  1/1 (100.00%)  1/1 (100.00%)  4/7 (57.14%)  4/19 (21.05%) 
Hypernatremia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Hypoalbuminemia  1  2/3 (66.67%)  2/3 (66.67%)  1/1 (100.00%)  0/1 (0.00%)  3/7 (42.86%)  7/19 (36.84%) 
Hypocalcemia  1  3/3 (100.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  2/7 (28.57%)  3/19 (15.79%) 
Hypoglycemia  1  0/3 (0.00%)  1/3 (33.33%)  1/1 (100.00%)  1/1 (100.00%)  0/7 (0.00%)  1/19 (5.26%) 
Hypokalemia  1  1/3 (33.33%)  2/3 (66.67%)  1/1 (100.00%)  0/1 (0.00%)  2/7 (28.57%)  3/19 (15.79%) 
Hypomagnesemia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  2/19 (10.53%) 
Hyponatremia  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  5/7 (71.43%)  3/19 (15.79%) 
Musculoskeletal and connective tissue disorders             
Back Pain  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Buttock Pain  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Generalized Muscle Weakness  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Muscle Weakness Lower Limb  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  2/19 (10.53%) 
Muscle Weakness Upper Limb  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Neck Pain  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Pain in Extremity  1  0/3 (0.00%)  0/3 (0.00%)  1/1 (100.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Nervous system disorders             
Abducens Nerve Disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Dizziness  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  2/7 (28.57%)  0/19 (0.00%) 
Dysgeusia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Headaches  1  1/3 (33.33%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  2/7 (28.57%)  3/19 (15.79%) 
Lethargy  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Memory Impairment  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Meningismus  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  2/19 (10.53%) 
Involuntary Movements  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Oculomotor Nerve Disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Peripheral Sensory Neuropathy  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Seizure  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  3/19 (15.79%) 
Syncope  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Paresthesia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Aphasia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Gait difficulty  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Psychiatric disorders             
Anxiety  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Confusion  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Insomnia  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Renal and urinary disorders             
Urinary incontinence  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  2/19 (10.53%) 
Urinary Frequency  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders             
Allergic Rhinitis  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Cough  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Epistaxis  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Hoarseness  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Hypoxia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Pneumonitis  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Respiratory Failure  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Skin and subcutaneous tissue disorders             
Alopecia  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  2/19 (10.53%) 
Dry Skin  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Pain of Skin  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Rash Acneiform  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Rash Maculo-papular  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Hand and Foot Syndrome  1  0/3 (0.00%)  0/3 (0.00%)  1/1 (100.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Vascular disorders             
Hematuria  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  1/19 (5.26%) 
Hypertension  1  0/3 (0.00%)  1/3 (33.33%)  0/1 (0.00%)  0/1 (0.00%)  6/7 (85.71%)  1/19 (5.26%) 
Hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  1/19 (5.26%) 
Hot Flashes  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  1/7 (14.29%)  0/19 (0.00%) 
Lymphedema  1  1/3 (33.33%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  0/19 (0.00%) 
Thromboembolic Event  1  0/3 (0.00%)  0/3 (0.00%)  0/1 (0.00%)  0/1 (0.00%)  0/7 (0.00%)  2/19 (10.53%) 
1
Term from vocabulary, CTCAE (4.03)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jeffrey Raizer, MD
Organization: Northwestern University
EMail: Jeffrey.Raizer@nm.org
Layout table for additonal information
Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT01325207    
Other Study ID Numbers: NU 10C03
STU00040150 ( Other Identifier: Northwestern University IRB )
First Submitted: March 7, 2011
First Posted: March 29, 2011
Results First Submitted: April 5, 2019
Results First Posted: May 28, 2019
Last Update Posted: September 26, 2019