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A Study Of Everolimus, Trastuzumab And Vinorelbine In HER2-Positive Breast Cancer Brain Metastases

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ClinicalTrials.gov Identifier: NCT01305941
Recruitment Status : Completed
First Posted : March 1, 2011
Results First Posted : October 17, 2017
Last Update Posted : December 17, 2018
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HER-2 Positive Breast Cancer
Interventions Drug: Everolimus
Drug: Vinorelbine
Drug: Trastuzumab
Enrollment 32
Recruitment Details Subjects were recruited from 4 institutions between September, 2011 and May, 2016.
Pre-assignment Details A total of 41 patients were consented to this study. Of these, 6 patients were found ineligible, 2 withdrew prior to treatment, and 1 patient has disease progression prior to protocol therapy. Therefore only 32 patients were enrolled and participated in the trial.
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Period Title: Overall Study
Started 32
Completed 22
Not Completed 10
Reason Not Completed
Adverse Event             6
Clinical decline             2
Withdrawal by Subject             1
Death             1
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 32 participants
53
(28 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
32
 100.0%
Male
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   3.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  12.5%
White
26
  81.3%
More than one race
0
   0.0%
Unknown or Not Reported
1
   3.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 32 participants
32
 100.0%
Stage at breast cancer diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
0-III
19
  59.4%
IV
13
  40.6%
[1]
Measure Description:

Anatomic stage for NSCLC is the American Joint Committee on Cancer (AJCC) tumor, node, and metastases (TNM) system, which is based on:

Size of primary tumor (T) and whether it has grown into nearby areas. Spread to regional lymph nodes (N). Spread (metastasis; M) to other organs of the body. Once the T, N, and M categories have been determined, this information is combined into a prognostic group. Higher numbers mean the cancer is more advanced.

Median time since first brain metastases (years)  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 32 participants
1.12
(0.4 to 6.5)
Prior Systemic Chemotherapy (metastatic)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
30
  93.8%
[1]
Measure Description: Number of participants who received prior systemic chemotherapy.
Prior metastatic chemotherapy lines, # (range)  
Median (Full Range)
Unit of measure:  Metastatic Lines
Number Analyzed 32 participants
2
(0 to 7)
Prior anti-Her2 (metastatic) Agents  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Trastuzumab
29
  90.6%
Lapatinib
22
  68.8%
Pertuzumab
12
  37.5%
Trastuzumab Emtansine (TDM-1)
8
  25.0%
Prior Central Nervous System Local Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Surgery
10
  31.3%
Whole brain radiation therapy
22
  68.8%
Stereotactic Radiosurgery (SRS)
17
  53.1%
Recursive Partitioning Analysis (RPA) Score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Class 1
10
  31.3%
Class 2
21
  65.6%
Class 3
1
   3.1%
[1]
Measure Description:

Recursive partitioning creates a decision tree that classifies members of a population by splitting it into sub-populations based on several dichotomous independent variables. The process is termed recursive because each sub-population may in turn be split an indefinite number of times.

This includes three classes: Class 1 (patients <65 years, ECOG Performance Status of 0-1, controlled primary tumor, and no extracranial metastases), Class 3 (ECOG Performance Status of 2 or greater), and Class 2 (all others);

Steroid use at baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
10
  31.3%
[1]
Measure Description: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation.
Extracranial disease at enrollment   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
20
  62.5%
[1]
Measure Description: Outside of the cranium (bones that surround the brain).
1.Primary Outcome
Title Intracranial Objective Response Rate- Modified RECIST Criteria
Hide Description

response will be evaluated via gadolinium-enhanced brain MRI using modified RECIST criteria.

Complete Response (CR) - Disappearance of all target and nontarget lesions

Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.

Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since the treatment started.

Progressive Disease (PD) – at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Six subjects were not evaluable for response because there was no follow-up disease assessment done due to poor clinical status of subjects
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response
0
   0.0%
Partial Response
1
   3.8%
Stable Disease
17
  65.4%
Progressive Disease
8
  30.8%
2.Secondary Outcome
Title Intracranial Response Rate- MacDonald Criteria
Hide Description

Intracranial tumor lesions were evaluated via gadolinium-enhanced brain MRI using the MacDonald criteria. Measurable disease is defined as at least 1 measurable brain lesion accurately measured in at least 2 dimensions (longest diameter) as ≥5.0 mm. Tumor size is the product of the 2 longest bi-dimensional lines.

Complete Response (CR)- Disappearance of all tumor on consecutive CT or MRI scans at least 1 month apart, off steroids for treatment of neurological symptoms, and neurologically stable or improved.

Partial Response (PR)- ≥50% reduction in size of tumor on consecutive CT or MRI scans at least 1 month part, steroids stable or reduced, and neurologically stable or improved.

Progressive Disease (PD)- ≥25% increase in size of tumor or any new tumor on CT or MRI scans, or neurologically worse, and steroids stable or increased due to neurologic symptoms.

Stable Disease (SD)- all other situations Overall Response Rate (ORR) is the sum of partial responses (PRs) and CRs.

Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Six subjects were not evaluable for response because there was no follow-up disease assessment done due to poor clinical status of subjects
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 26
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.8%
3.Secondary Outcome
Title Toxicity
Hide Description

Grade 3 or higher toxicities of interest are reported. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.

The NCI CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Time Frame 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 32
Measure Type: Count of Participants
Unit of Measure: Participants
Alkaline phosphatase increased
1
   3.1%
Anemia
5
  15.6%
Anorexia
1
   3.1%
Asparate Aminotransferase Increased
2
   6.3%
Diarrhea
1
   3.1%
Febrile Neutropenia
2
   6.3%
Hyperkalemia
1
   3.1%
Lymphocyte Count Decreased
3
   9.4%
Mucositis Oral
5
  15.6%
Neutrophil Count Decreased
13
  40.6%
Pneumonitis
1
   3.1%
Sepsis
3
   9.4%
White Blood Cell Decreased
11
  34.4%
4.Secondary Outcome
Title Time to Intracranial Progression.
Hide Description

Time to intracranial progression after administration of everolimus in combination with trastuzumab and vinorelbine as defined via modified RECIST criteria.

Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 32
Median (95% Confidence Interval)
Unit of Measure: months
3.93
(2.27 to 5.00)
5.Secondary Outcome
Title Extracranial Response
Hide Description

Extracranial response was measured using RECIST 1.1 criteria and defined as the number of subjects achieving CR or PR.

Complete Response (CR) - Disappearance of all target and nontarget lesions Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum longest diameter AND an absolute decrease of at least 5mm in at least one target lesion.

Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameter since the treatment started.

Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Seven subjects were not evaluable for extra-cranial response because there was no follow-up disease assessment done due to poor clinical status of subjects. An additional 12 subjects were excluded since they did not have extra-cranial disease at baseline and one additional subject was non compliant for follow-up scans.
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 12
Measure Type: Count of Participants
Unit of Measure: Participants
5
  41.7%
6.Secondary Outcome
Title Extracranial Time to Progression
Hide Description

To evaluate the extracranial time to progression as determined by RECIST 1.1 criteria after administration of everolimus in combination with trastuzumab and vinorelbine.

Progressive Disease (PD) - at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started AND an absolute increase in size of at least 5 mm in at least one target lesion OR the appearance of one or more new lesions of at least 6 mm in size.

Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Seven subjects were not evaluable for extra-cranial response due to no follow-up disease assessments due to poor clinical status; 12 subjects were excluded since they did not have extra-cranial disease at baseline; 1 subject was non compliant for follow-up scans; and 1 subject was excluded due to intracranial progression prior to extracranial.
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: months
4.01
(1.97 to 8.26)
7.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) after administration of everolimus in combination with trastuzumab and vinorelbine
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 32
Median (95% Confidence Interval)
Unit of Measure: years
1.01
(.57 to 1.78)
8.Secondary Outcome
Title Functional Assessment of Cancer Therapy- Brain (FACT-Br) Change From Baseline to Assess Impact of Everolimus in Combination With Trastuzumab and Vinorelbine on Quality of Life
Hide Description The FACT-Br is a 23-question self-report questionnaire subscale administered with the Functional Assessment of Cancer Therapy- General (FACT-G) which contains concerns relevant to patients with brain tumors . Each question has a value 0-4. For some questions a higher indicates better outcome and others are the opposite. The former are summed as is, the latter are reversed in value before adding, such that each domain ranges from 0 to 4 times the number of questions in the domain, with 0 indicating worst and the highest possible value indicating best outcome. Total scores on the FACT-Br subscale range from 0 to 92 with lower scores indicating declining quality of life. The change from baseline is the difference in scores between the baseline and 9 week assessments.
Time Frame 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Quality of life was an optional assessment for patients, so results are only reported for subjects who completed questionnaires at each timepoint
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 9
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
-1.0
(-5.0 to 4.8)
9.Secondary Outcome
Title Functional Assessment Cancer Therapy- Breast (FACT-B) From Baseline to 9 Weeks of Treatment to Assess Impact of Everolimus in Combination With Trastuzumab and Vinorelbine on Quality of Life
Hide Description The FACT-B is a 10-question self-report questionnaire subscale administered with the Functional Assessment of Cancer Therapy- General (FACT-G) which contains concerns relevant to patients with breast cancer. Each question has a value 0-4. For some questions a higher indicates better outcome and others are the opposite. The former are summed as is, the latter are reversed in value before adding, such that each domain ranges from 0 to 4 times the number of questions in the domain, with 0 indicating worst and the highest possible value indicating best outcome. Total scores on the FACT-B subscale range from 0 to 40 with lower scores indicating declining quality of life. The change from baseline is the difference in scores between the baseline and 9 week assessments.
Time Frame 9 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Quality of life was an optional assessment for patients, so results are only reported for subjects who completed questionnaires at each timepoint
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description:

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

Overall Number of Participants Analyzed 11
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
1.0
(-2.0 to 3.0)
Time Frame 24 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Everolimus +Vinorelbine + Trastuzumab
Hide Arm/Group Description

daily everolimus plus weekly (Days 1, 8, and 15) vinorelbine and trastuzumab

Everolimus: everolimus 5 mg PO daily as two 2.5-mg tablets

Vinorelbine: vinorelbine 25 mg/m2 will be administered via IV infusion over 6-10 minutes weekly.

Trastuzumab: 2 mg/kg IV administered over 30 minutes weekly

All-Cause Mortality
Everolimus +Vinorelbine + Trastuzumab
Affected / at Risk (%)
Total   29/32 (90.63%) 
Show Serious Adverse Events Hide Serious Adverse Events
Everolimus +Vinorelbine + Trastuzumab
Affected / at Risk (%)
Total   13/32 (40.63%) 
Blood and lymphatic system disorders   
Anemia * 1  1/32 (3.13%) 
Endocrine disorders   
Adrenal Insufficiency * 1  1/32 (3.13%) 
Gastrointestinal disorders   
Vomiting * 1  1/32 (3.13%) 
General disorders   
Fever * 1  2/32 (6.25%) 
Infusion related reaction * 1  1/32 (3.13%) 
Pain * 1  1/32 (3.13%) 
Immune system disorders   
Anaphylaxis * 1  1/32 (3.13%) 
Infections and infestations   
Lung Infection * 1  1/32 (3.13%) 
Sepsis * 1  3/32 (9.38%) 
Upper Respiratory Infection * 1  1/32 (3.13%) 
Investigations   
Creatinine Increased * 1  2/32 (6.25%) 
Metabolism and nutrition disorders   
Hyperkalemia * 1  1/32 (3.13%) 
Hyperuricemia * 1  1/32 (3.13%) 
Musculoskeletal and connective tissue disorders   
Bone Pain * 1  1/32 (3.13%) 
Muscle Weakness Lower Limb * 1  1/32 (3.13%) 
Nervous system disorders   
Seizure * 1  2/32 (6.25%) 
Tremor * 1  1/32 (3.13%) 
Psychiatric disorders   
Confusion * 1  1/32 (3.13%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia * 1  1/32 (3.13%) 
Laryngeal Hemorrhage * 1  1/32 (3.13%) 
Pneumonitis * 1  1/32 (3.13%) 
Vascular disorders   
Hypotension * 1  1/32 (3.13%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Everolimus +Vinorelbine + Trastuzumab
Affected / at Risk (%)
Total   32/32 (100.00%) 
Blood and lymphatic system disorders   
Anemia * 1  11/32 (34.38%) 
Febrile neutropenia * 1  2/32 (6.25%) 
Eye disorders   
Eye Disorders - Other, Specify * 1 [1]  2/32 (6.25%) 
Gastrointestinal disorders   
Abdominal pain * 1  2/32 (6.25%) 
Constipation * 1  12/32 (37.50%) 
Diarrhea * 1  8/32 (25.00%) 
Gastroesophageal reflux disease * 1  2/32 (6.25%) 
Mucositis oral * 1  21/32 (65.63%) 
Nausea * 1  7/32 (21.88%) 
Vomiting * 1  4/32 (12.50%) 
General disorders   
Edema limbs * 1  3/32 (9.38%) 
Fatigue * 1  14/32 (43.75%) 
Flu like symptoms * 1  2/32 (6.25%) 
Pain * 1  7/32 (21.88%) 
Infections and infestations   
Infections And Infestations - Other, Specify * 1 [2]  2/32 (6.25%) 
Mucosal infection * 1  2/32 (6.25%) 
Papulopustular rash * 1  2/32 (6.25%) 
Upper respiratory infection * 1  4/32 (12.50%) 
Urinary tract infection * 1  8/32 (25.00%) 
Injury, poisoning and procedural complications   
Bruising * 1  2/32 (6.25%) 
Fall * 1  2/32 (6.25%) 
Investigations   
Alanine aminotransferase increased * 1  9/32 (28.13%) 
Alkaline phosphatase increased * 1  4/32 (12.50%) 
Aspartate aminotransferase increased * 1  9/32 (28.13%) 
Blood bilirubin increased * 1  3/32 (9.38%) 
Creatinine increased * 1  3/32 (9.38%) 
Lymphocyte count decreased * 1  6/32 (18.75%) 
Neutrophil count decreased * 1  17/32 (53.13%) 
Platelet count decreased * 1  7/32 (21.88%) 
Weight loss * 1  2/32 (6.25%) 
White blood cell decreased * 1  15/32 (46.88%) 
Metabolism and nutrition disorders   
Anorexia * 1  10/32 (31.25%) 
Hyperglycemia * 1  4/32 (12.50%) 
Hypoalbuminemia * 1  2/32 (6.25%) 
Hypocalcemia * 1  2/32 (6.25%) 
Hypokalemia * 1  5/32 (15.63%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  3/32 (9.38%) 
Bone pain * 1  2/32 (6.25%) 
Flank pain * 1  2/32 (6.25%) 
Generalized muscle weakness * 1  3/32 (9.38%) 
Muscle weakness lower limb * 1  2/32 (6.25%) 
Musculoskeletal And Connective Tissue Disorder - Other, Specify * 1 [3]  6/32 (18.75%) 
Myalgia * 1  3/32 (9.38%) 
Pain in extremity * 1  2/32 (6.25%) 
Nervous system disorders   
Dizziness * 1  2/32 (6.25%) 
Dysphasia * 1  2/32 (6.25%) 
Headache * 1  11/32 (34.38%) 
Memory impairment * 1  2/32 (6.25%) 
Peripheral sensory neuropathy * 1  9/32 (28.13%) 
Psychiatric disorders   
Anxiety * 1  3/32 (9.38%) 
Depression * 1  5/32 (15.63%) 
Insomnia * 1  6/32 (18.75%) 
Renal and urinary disorders   
Acute kidney injury * 1  2/32 (6.25%) 
Proteinuria * 1  2/32 (6.25%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  6/32 (18.75%) 
Dyspnea * 1  3/32 (9.38%) 
Epistaxis * 1  3/32 (9.38%) 
Nasal congestion * 1  3/32 (9.38%) 
Pneumonitis * 1  2/32 (6.25%) 
Respiratory, Thoracic And Mediastinal Disorders - Other, Specify * 1 [4]  2/32 (6.25%) 
Sore throat * 1  2/32 (6.25%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  4/32 (12.50%) 
Pruritus * 1  2/32 (6.25%) 
Rash acneiform * 1  6/32 (18.75%) 
Rash maculo-papular * 1  3/32 (9.38%) 
Skin And Subcutaneous Tissue Disorders - Other, Specify * 1 [5]  2/32 (6.25%) 
Vascular disorders   
Hypertension * 1  2/32 (6.25%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
[1]
Verbatim: Dry eyelids; Eye muscle twitching
[2]
Verbatim:infection to right thumb - laceration; folliculitis - facial; Right groin - sebaceous cyst or tiny abcess
[3]
Verbatim:Muscle cramps; muscle spasms-hands; Back muscle spasms; Cramping of feet and hands;Hand and jaw cramping; cramping legs
[4]
Verbatim: Rhinorrhea; Nasal drainage clear, sometimes small amounts of blood
[5]
Verbatim: Contact Dermatitis Bilateral Hands; Dermatitis (earlobes); blepharitis left eyelid
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Robin V. Johnson
Organization: UNC Comprehensive Cancer Center
Phone: 919-966-1125
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01305941     History of Changes
Other Study ID Numbers: LCCC 1025
11-0242 ( Other Identifier: UNC IRB assigned protocol number )
First Submitted: February 25, 2011
First Posted: March 1, 2011
Results First Submitted: July 28, 2017
Results First Posted: October 17, 2017
Last Update Posted: December 17, 2018