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Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax

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ClinicalTrials.gov Identifier: NCT01570036
Recruitment Status : Completed
First Posted : April 4, 2012
Results First Posted : December 2, 2020
Last Update Posted : December 2, 2020
Sponsor:
Collaborators:
Genentech, Inc.
Sellas Life Sciences Group
Information provided by (Responsible Party):
George E. Peoples, Cancer Insight, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Prevention
Condition Breast Cancer
Interventions Drug: Herceptin
Drug: NeuVax vaccine
Drug: GM-CSF
Enrollment 275
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Hide Arm/Group Description Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion.
Period Title: Overall Study
Started 136 139
Primary Vaccine Series Completed 121 132
Booster Series Completed 40 30
Completed 18 17
Not Completed 118 122
Arm/Group Title Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only Total
Hide Arm/Group Description Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion. Total of all reporting groups
Overall Number of Baseline Participants 136 139 275
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 136 participants 139 participants 275 participants
52.2
(43.7 to 60.8)
50.5
(42 to 59)
51.6
(43.9 to 61.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 136 participants 139 participants 275 participants
Female
136
 100.0%
139
 100.0%
275
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 136 participants 139 participants 275 participants
109
  80.1%
97
  69.8%
206
  74.9%
Asian Number Analyzed 136 participants 139 participants 275 participants
2
   1.5%
9
   6.5%
11
   4.0%
Black Number Analyzed 136 participants 139 participants 275 participants
13
   9.6%
20
  14.4%
33
  12.0%
Hispanic Number Analyzed 136 participants 139 participants 275 participants
10
   7.4%
9
   6.5%
19
   6.9%
Unknown Number Analyzed 136 participants 139 participants 275 participants
2
   1.5%
4
   2.9%
6
   2.2%
Nottingham modified, Scarff-Bloom-Richardson Grade   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Grade 1 Number Analyzed 136 participants 139 participants 275 participants
8
   5.9%
14
  10.1%
22
   8.0%
Grade 2 Number Analyzed 136 participants 139 participants 275 participants
57
  41.9%
56
  40.3%
113
  41.1%
Grade 3 Number Analyzed 136 participants 139 participants 275 participants
69
  50.7%
69
  49.6%
138
  50.2%
[1]
Measure Description: Pathological grading system based on tumor tubule formation, number of mitotic figures in most active areas and nuclear pleomorphism. Each of these factors is given points 1-3 for a total of 3-9 points. The overall scores are broken down as 3 - 5 points (well differentiated (grade I)), 6 - 7 points (moderately differentiated (grade II)), and 8 - 9 points (poorly differentiated (grade III)).
Hormone receptor status  
Measure Type: Count of Participants
Unit of measure:  Participants
ER Positive Number Analyzed 136 participants 139 participants 275 participants
81
  59.6%
95
  68.3%
176
  64.0%
PR Positive Number Analyzed 136 participants 139 participants 275 participants
77
  56.6%
83
  59.7%
160
  58.2%
Triple Negative Number Analyzed 136 participants 139 participants 275 participants
53
  39.0%
44
  31.7%
97
  35.3%
HER2 Immunohistochemistry (IHC)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
IHC 1+ Number Analyzed 136 participants 139 participants 275 participants
89
  65.4%
89
  64.0%
178
  64.7%
IHC 2+ Number Analyzed 136 participants 139 participants 275 participants
47
  34.6%
50
  36.0%
97
  35.3%
[1]
Measure Description: IHC 1+ is incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumor cells. IHC 2+ is a weak to moderate complete membrane staining is observed in >10% of tumor cells OR strong complete membrane staining in </= 10% of tumor cells.
Breast surgery  
Measure Type: Count of Participants
Unit of measure:  Participants
Breast Conservation Therapy Number Analyzed 136 participants 139 participants 275 participants
39
  28.7%
34
  24.5%
73
  26.5%
Mastectomy Number Analyzed 136 participants 139 participants 275 participants
97
  71.3%
104
  74.8%
201
  73.1%
None Number Analyzed 136 participants 139 participants 275 participants
0
   0.0%
1
   0.7%
1
   0.4%
Chemotherapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Neoadjuvant Number Analyzed 136 participants 139 participants 275 participants
72
  52.9%
76
  54.7%
148
  53.8%
Adjuvant Number Analyzed 136 participants 139 participants 275 participants
59
  43.4%
57
  41.0%
116
  42.2%
None Number Analyzed 136 participants 139 participants 275 participants
5
   3.7%
6
   4.3%
11
   4.0%
Radiation with Breast Conservation Therapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Adjuvant Number Analyzed 39 participants 34 participants 73 participants
39
 100.0%
34
 100.0%
73
 100.0%
None Number Analyzed 39 participants 34 participants 73 participants
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Only evaluable for patients that underwent breast conservation therapy.
Radiation with Mastectomy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Adjuvant Number Analyzed 97 participants 104 participants 201 participants
76
  78.4%
89
  85.6%
165
  82.1%
Neoadjuvant Number Analyzed 97 participants 104 participants 201 participants
2
   2.1%
0
   0.0%
2
   1.0%
None Number Analyzed 97 participants 104 participants 201 participants
19
  19.6%
15
  14.4%
34
  16.9%
[1]
Measure Analysis Population Description: Only evaluable for patients that underwent mastectomy.
Axillary Surgery  
Measure Type: Count of Participants
Unit of measure:  Participants
Axillary Dissection Number Analyzed 136 participants 139 participants 275 participants
81
  59.6%
88
  63.3%
169
  61.5%
Sentinel Lymph Node Biopsy Number Analyzed 136 participants 139 participants 275 participants
55
  40.4%
48
  34.5%
103
  37.5%
None Number Analyzed 136 participants 139 participants 275 participants
0
   0.0%
3
   2.2%
3
   1.1%
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Unknown Number Analyzed 72 participants 76 participants 148 participants
1
   1.4%
2
   2.6%
3
   2.0%
0 Number Analyzed 72 participants 76 participants 148 participants
0
   0.0%
1
   1.3%
1
   0.7%
I Number Analyzed 72 participants 76 participants 148 participants
4
   5.6%
3
   3.9%
7
   4.7%
IIA Number Analyzed 72 participants 76 participants 148 participants
16
  22.2%
13
  17.1%
29
  19.6%
IIB Number Analyzed 72 participants 76 participants 148 participants
19
  26.4%
18
  23.7%
37
  25.0%
IIIA Number Analyzed 72 participants 76 participants 148 participants
14
  19.4%
25
  32.9%
39
  26.4%
IIIB Number Analyzed 72 participants 76 participants 148 participants
7
   9.7%
2
   2.6%
9
   6.1%
IIIC Number Analyzed 72 participants 76 participants 148 participants
10
  13.9%
13
  17.1%
23
  15.5%
IV* Number Analyzed 72 participants 76 participants 148 participants
1
   1.4%
0
   0.0%
1
   0.7%
[1]
Measure Description:

Stage 0 is not cancer, abnormal cells are present but not spread Stage I-III Cancer is present. The higher number, the larger tumor & more spread to nearby tissues Stage IV Cancer has distant body part spread(AJCC, 7th Ed) Clinical staging occurs prior to neoadjuvant chemo Only neoadjuvant chemotherapy patients included

*1 patient with path. stage IIB after completion of chemo was enrolled & vaccinated. It was discovered the patient had metastatic disease prior to initiation chemotherapy & enrolled in protocol violation. The patient was in eligible & excluded from efficacy analyses.

[2]
Measure Analysis Population Description: Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Unknown Number Analyzed 72 participants 76 participants 148 participants
1
   1.4%
0
   0.0%
1
   0.7%
0 Number Analyzed 72 participants 76 participants 148 participants
5
   6.9%
4
   5.3%
9
   6.1%
I Number Analyzed 72 participants 76 participants 148 participants
11
  15.3%
9
  11.8%
20
  13.5%
IIA Number Analyzed 72 participants 76 participants 148 participants
16
  22.2%
15
  19.7%
31
  20.9%
IIB Number Analyzed 72 participants 76 participants 148 participants
12
  16.7%
11
  14.5%
23
  15.5%
IIIA Number Analyzed 72 participants 76 participants 148 participants
11
  15.3%
20
  26.3%
31
  20.9%
IIIB Number Analyzed 72 participants 76 participants 148 participants
4
   5.6%
3
   3.9%
7
   4.7%
IIIC Number Analyzed 72 participants 76 participants 148 participants
12
  16.7%
14
  18.4%
26
  17.6%
[1]
Measure Description:

Stage 0 is not cancer, abnormal cells are present but not spread Stage I-III Cancer is present. The higher number, the larger tumor & more spread to nearby tissues Stage IV Cancer has distant body part spread

The American Joint Committee on Cancer, 7th Edition Staging was used for this analysis (https://cancerstaging.org/references-tools/quickreferences/Documents/BreastMedium.pdf).

Pathologic staging occurs after patients have undergone surgical therapy.

Only neoadjuvant chemotherapy patients included into this patient count.

[2]
Measure Analysis Population Description: Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
I Number Analyzed 64 participants 63 participants 127 participants
10
  15.6%
9
  14.3%
19
  15.0%
IIA Number Analyzed 64 participants 63 participants 127 participants
11
  17.2%
12
  19.0%
23
  18.1%
IIB Number Analyzed 64 participants 63 participants 127 participants
14
  21.9%
14
  22.2%
28
  22.0%
IIIA Number Analyzed 64 participants 63 participants 127 participants
21
  32.8%
18
  28.6%
39
  30.7%
IIIB Number Analyzed 64 participants 63 participants 127 participants
0
   0.0%
0
   0.0%
0
   0.0%
IIIC Number Analyzed 64 participants 63 participants 127 participants
8
  12.5%
10
  15.9%
18
  14.2%
[1]
Measure Description:

Stage 0 is not cancer, abnormal cells are present but not spread Stage I-III Cancer is present. The higher number, the larger tumor & more spread to nearby tissues Stage IV Cancer has distant body part spread

The American Joint Committee on Cancer, 7th Edition Staging was used for this analysis (https://cancerstaging.org/references-tools/quickreferences/Documents/BreastMedium.pdf).

Pathologic staging is performed after the patients have undergone surgical therapy; these patient did not receive neoadjuvant chemotherapy.

[2]
Measure Analysis Population Description: The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).
1.Primary Outcome
Title Disease-free Survival (DFS)
Hide Description Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur every three months for the first 24 months after completion of primary therapies and every six months thereafter with clinical exam, and laboratory and radiographic surveillance. The primary objective of the study is disease-free survival (DFS) at 24 months.
Time Frame Disease-free survival at 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Hide Arm/Group Description:
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months.
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion.
Overall Number of Participants Analyzed 136 139
Measure Type: Number
Unit of Measure: Percentage of participants who survived
89.8 83.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments [Not Specified]
Type of Statistical Test Other
Comments Kaplan-Meier Survival Analysis
Statistical Test of Hypothesis P-Value 0.18
Comments [Not Specified]
Method Kaplan-Meier Survival Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
.31 to 1.25
Estimation Comments [Not Specified]
2.Primary Outcome
Title Disease-free Survival (DFS)
Hide Description Disease-free survival (DFS) for all patients regardless of randomization will be determined by patients' own physicians at the individual study sites during routine follow-up screening. This will occur at months 30 and 36 after completion of primary therapies with clinical exam, and laboratory and radiographic surveillance. The secondary objective of the study is disease-free survival (DFS) at 36 months.
Time Frame Disease-free survival up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Hide Arm/Group Description:
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months.
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion.
Overall Number of Participants Analyzed 136 139
Measure Type: Number
Unit of Measure: Percent Survival
86.7 80.8
3.Secondary Outcome
Title Percent Ejection Fraction - A Measure of Cardiac Toxicity
Hide Description Each patient, regardless of randomization, will undergo cardiac assessment (ejection fraction) of Multiple Gated Acquisition scan (MUGA) preferred, echocardiogram (ECHO) allowed, consistency required) at baseline, 3 months, 6 months, 12 months, and 24 months. Cardiac assessment will continue every six months if a patient experiences a greater than 10% reduction from baseline for the duration of the trial or until resolution.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on those patients with data at each specified time point.
Arm/Group Title Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Hide Arm/Group Description:
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months.
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion.
Overall Number of Participants Analyzed 136 137
Mean (Standard Error)
Unit of Measure: Percent Ejection Fraction
Baseline Number Analyzed 136 participants 137 participants
60.82  (.61) 61.47  (.47)
3 Months Number Analyzed 126 participants 121 participants
59.49  (.54) 59.56  (.54)
6 Months Number Analyzed 116 participants 112 participants
59.92  (.88) 60.07  (.57)
12 Months Number Analyzed 96 participants 87 participants
59.39  (.56) 59.7  (.57)
24 Months Number Analyzed 54 participants 43 participants
61.05  (.79) 61.09  (.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments Comparison of the mean LVEF from baseline to 3 months, 6 months, and 12 months; this time period includes the therapy period of trastuzumab.
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments The mean LVEF compared at baseline to 3 months, 6 months, 12 months and 24 months; this time period includes the duration of trastuzumab therapy and 1 year after completion of trastuzumab therapy.
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments Evaluating LVEF at all time points with a linear mixed regression model, this analysis compared cardiac ejection fraction over time.
Method Regression, Linear
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.91
Comments This analysis evaluated LVEF at all time points with a linear mixed regression model between randomization arms.
Method Regression, Linear
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments This analysis evaluated LVEF at all time points with a linear mixed regression model between the arms over time.
Method Regression, Linear
Comments [Not Specified]
4.Secondary Outcome
Title Local and Systemic Toxicities
Hide Description Standard local and systemic toxicities will be collected and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 toxicity scale. For both the regular and booster inoculations, patients will be monitored closely for one hour after inoculation with questioning, serial exams and vital signs every 15 minutes to observe for a hypersensitivity reaction. Patients will also return to the clinic 48-72 hours after each inoculation for questioning regarding systemic toxicity and to examine and measure the local reaction at the inoculation sites. Reported are the maximum related and graded adverse events per patient.
Time Frame Duration of vaccine or inoculation series and booster series, an average of 30 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis was performed only on patients that received NeuVax or Control.
Arm/Group Title Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Hide Arm/Group Description:
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months.
Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion.
Overall Number of Participants Analyzed 129 132
Measure Type: Number
Unit of Measure: Percent Experiencing
Local Grade 1 82.3 55.7
Local Grade 2 15.0 33.0
Local Grade 3 2.7 11.3
Systemic Grade 1 79.6 58.5
Systemic Grade 2 20.4 30.2
Systemic Grade 3 0 11.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments The safety group consisted of any patients who received NPS with GM-CSF or placebo with GM-CSF inoculations.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.149
Comments [Not Specified]
Method Chi-squared
Comments Comparison of the maximum related local toxicity experienced per patient and compared between treatment arms.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Herceptin + NeuVax Vaccine, Herceptin + GM-CSF Only
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.901
Comments [Not Specified]
Method Chi-squared
Comments Comparison of the maximum related systemic toxicity experienced per patient and compared between treatment arms.
Time Frame The duration of the trial, up to 36 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Hide Arm/Group Description Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year; the first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive vaccinations of NeuVax vaccine administered intradermally every 3 weeks for 6 total vaccinations, 30-120 minutes after completion of Herceptin infusion. The NeuVax vaccine series will begin immediately after completion of the third Herceptin infusion, but may be delayed to the fourth or fifth Herceptin infusion with prior approval from the PI. After completion of primary vaccine series, patients will receive NeuVax vaccine booster inoculations to be administered every 6 months x 4 for total treatment duration of 30 months. Patients randomized to this arm will receive Herceptin every 3 weeks as monotherapy for 1 year. The first Herceptin infusion will be given no sooner than 3 weeks and no later than 12 weeks after completion of standard of care chemotherapy/radiotherapy. Herceptin will be dosed at the recommended initial loading dose of 8 mg/kg and at recommended maintenance doses of 6 mg/kg q3wk. Patients will receive inoculations of GM-CSF only (250mcg) administered intradermally every 3 weeks for 6 total inoculations, 30-120 minutes after completion of Herceptin infusion. The GM-CSF only inoculation series will begin immediately after completion of the third Herceptin infusion. After completion of six-inoculation primary vaccine series, patients will then receive a total of four GM-CSF only booster inoculations to be administered at 12, 18, 24, and 30 months from the date of the first Herceptin infusion.
All-Cause Mortality
Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Affected / at Risk (%) Affected / at Risk (%)
Total   1/136 (0.74%)      0/139 (0.00%)    
Hide Serious Adverse Events
Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/136 (10.29%)      12/139 (8.63%)    
Blood and lymphatic system disorders     
Anemia  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Cardiac disorders     
Atrial fibrillation  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Heart failure  [1]  1/136 (0.74%)  1 1/139 (0.72%)  2
Sinus tachycardia  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Gastrointestinal disorders     
Colonic hemorrhage  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Esophageal obstruction  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Pancreatitis  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
General disorders     
Fever  [1]  1/136 (0.74%)  2 0/139 (0.00%)  0
Hepatobiliary disorders     
Other, specify  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Immune system disorders     
Allergic reaction  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Infections and infestations     
Skin Infection  [2]  1/136 (0.74%)  1 1/139 (0.72%)  1
Breast infection  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Device related infection  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Skin Infection  [1]  1/136 (0.74%)  2 0/139 (0.00%)  0
Soft tissue infection  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Wound infection  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Injury, poisoning and procedural complications     
Fracture  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Spinal fracture  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Wound complication  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Investigations     
Creatinine increased  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Metabolism and nutrition disorders     
Hyperglycemia  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Other, specify  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Nervous system disorders     
Edema cerebral  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Seizure  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Syncope  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Renal and urinary disorders     
Urinary tract obstruction  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnea  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Other, specify  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Vascular disorders     
Thromboembolic event  [1]  2/136 (1.47%)  2 2/139 (1.44%)  2
Indicates events were collected by systematic assessment
[1]
Systemic
[2]
Local
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Herceptin + NeuVax Vaccine Herceptin + GM-CSF Only
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   136      139    
Blood and lymphatic system disorders     
Other, specify  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Anemia  [1]  5/136 (3.68%)  12 5/139 (3.60%)  5
Cardiac disorders     
Other, specify  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Palpitations  [1]  4/136 (2.94%)  4 6/139 (4.32%)  6
Left ventricular systolic dysfunction  [1]  3/136 (2.21%)  3 4/139 (2.88%)  4
Right ventricular dysfunction  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Heart failure  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Supraventricular tachycardia  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Sinus tachycardia  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Atrial flutter  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Atrial fibrillation  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Aortic valve disease  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Ear and labyrinth disorders     
Other, specify  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Tinnitus  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Tinnitus  [1]  2/136 (1.47%)  2 1/139 (0.72%)  1
Vertigo  [1]  2/136 (1.47%)  2 1/139 (0.72%)  1
Hearing impaired  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Ear pain  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Endocrine disorders     
Other, specify  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Hypothyroidism  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Hyperthyroidism  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Eye disorders     
Other, specify  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Watering eyes  [2]  0/136 (0.00%)  0 2/139 (1.44%)  2
Uveitis  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Eyelid function disorder  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Other, specify  [1]  4/136 (2.94%)  5 1/139 (0.72%)  4
Watering eyes  [1]  1/136 (0.74%)  1 4/139 (2.88%)  4
Blurred vision  [1]  1/136 (0.74%)  6 0/139 (0.00%)  0
Floaters  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Conjuctivitis  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Optic nerve disorder  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Dry eye  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Cataract  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Gastrointestinal disorders     
Nausea  [2]  1/136 (0.74%)  1 2/139 (1.44%)  2
Other, specify  [2]  1/136 (0.74%)  1 2/139 (1.44%)  2
Diarrhea  [2]  0/136 (0.00%)  0 2/139 (1.44%)  2
Abdominal pain  [2]  0/136 (0.00%)  0 2/139 (1.44%)  2
Anal hemorrhage  [2]  1/136 (0.74%)  2 0/139 (0.00%)  0
Toothache  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Dental abscess  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Chelitis  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Nausea  [1]  38/136 (27.94%)  87 38/139 (27.34%)  88
Other, specify  [1]  8/136 (5.88%)  9 3/139 (2.16%)  4
Diarrhea  [1]  25/136 (18.38%)  48 16/139 (11.51%)  29
Abdominal pain  [1]  8/136 (5.88%)  9 7/139 (5.04%)  13
Vomiting  [1]  9/136 (6.62%)  11 10/139 (7.19%)  12
Constipation  [1]  6/136 (4.41%)  11 7/139 (5.04%)  7
GERD  [1]  4/136 (2.94%)  4 7/139 (5.04%)  10
Dyspepsia  [1]  4/136 (2.94%)  5 6/139 (4.32%)  6
Mucositis oral  [1]  2/136 (1.47%)  2 4/139 (2.88%)  5
Bloating  [1]  2/136 (1.47%)  2 2/139 (1.44%)  2
Flatulence  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Oral pain  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Hemorrhoids  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Pancreatitis  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Esophageal obstruction  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Dry mouth  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Colonic hemorrhage  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Colitis  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
General disorders     
Injection site reaction  [2]  109/136 (80.15%)  846 102/139 (73.38%)  698
Fatigue  [2]  2/136 (1.47%)  2 1/139 (0.72%)  1
Pain  [2]  49/136 (36.03%)  140 32/139 (23.02%)  83
Other, specify  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Malaise  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Chills  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Flu like symptoms  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Edema limbs  [2]  1/136 (0.74%)  4 2/139 (1.44%)  3
Infusion related reaction  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Localized edema  [2]  1/136 (0.74%)  1 1/139 (0.72%)  1
Facial pain  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Injection site reaction  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Fatigue  [1]  70/136 (51.47%)  236 69/139 (49.64%)  188
Pain  [1]  3/136 (2.21%)  3 4/139 (2.88%)  4
Other, specify  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Malaise  [1]  30/136 (22.06%)  79 28/139 (20.14%)  64
Chills  [1]  29/136 (21.32%)  55 29/139 (20.86%)  52
Flu like symptoms  [1]  23/136 (16.91%)  36 26/139 (18.71%)  38
Fever  [1]  14/136 (10.29%)  18 15/139 (10.79%)  22
Edema limbs  [1]  11/136 (8.09%)  11 7/139 (5.04%)  8
Non-cardiac chest pain  [1]  4/136 (2.94%)  4 6/139 (4.32%)  7
Irritability  [1]  0/136 (0.00%)  0 1/139 (0.72%)  4
Infusion related reaction  [1]  3/136 (2.21%)  3 0/139 (0.00%)  0
Localized edema  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Edema face  [1]  2/136 (1.47%)  2 1/139 (0.72%)  1
Edema trunk  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Gait distrubance  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Hepatobiliary disorders     
Other, specify  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Immune system disorders     
Allergic reaction  [2]  0/136 (0.00%)  0 1/139 (0.72%)  2
Allergic reaction  [1]  7/136 (5.15%)  9 6/139 (4.32%)  6
Autoimmune disorder  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Anaphylaxis  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Infections and infestations     
Upper respiratory infection  [2]  1/136 (0.74%)  2 1/139 (0.72%)  1
Sinusitis  [2]  1/136 (0.74%)  1 1/139 (0.72%)  1
Skin infection  [2]  3/136 (2.21%)  3 1/139 (0.72%)  1
Breast infection  [2]  1/136 (0.74%)  1 1/139 (0.72%)  1
Lip infection  [2]  0/136 (0.00%)  0 1/139 (0.72%)  2
Otitis media  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Wound infection  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Pharyngitis  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Device related infection  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Eye infection  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Other, specify  [1]  5/136 (3.68%)  6 2/139 (1.44%)  2
Upper respiratory infection  [1]  12/136 (8.82%)  16 9/139 (6.47%)  12
Sinusitis  [1]  9/136 (6.62%)  12 7/139 (5.04%)  10
Urinary tract infection  [1]  6/136 (4.41%)  6 5/139 (3.60%)  7
Skin infection  [1]  4/136 (2.94%)  4 1/139 (0.72%)  1
Breast infection  [1]  2/136 (1.47%)  2 3/139 (2.16%)  3
Skin infection  [1]  3/136 (2.21%)  3 2/139 (1.44%)  2
Vaginal infection  [1]  2/136 (1.47%)  3 2/139 (1.44%)  2
Lip infection  [1]  2/136 (1.47%)  2 1/139 (0.72%)  1
Bronchial infection  [1]  3/136 (2.21%)  4 1/139 (0.72%)  1
Otitis media  [1]  2/136 (1.47%)  2 1/139 (0.72%)  1
Wound infection  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Pharyngitis  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Papulopustular rash  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Nail infection  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Mucosal infection  [1]  1/136 (0.74%)  2 0/139 (0.00%)  0
Laryngitis  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Device related infection  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Bladder infection  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Tooth infection  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Paronychia  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Lung infection  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Anorectal infection  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Injury, poisoning and procedural complications     
Other, specify  [2]  1/136 (0.74%)  1 1/139 (0.72%)  1
Bruising  [2]  10/136 (7.35%)  12 10/139 (7.19%)  14
Fracture  [2]  2/136 (1.47%)  2 0/139 (0.00%)  0
Seroma  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Burn  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Other, specify  [1]  2/136 (1.47%)  2 1/139 (0.72%)  1
Bruising  [1]  1/136 (0.74%)  2 3/139 (2.16%)  3
Fracture  [1]  3/136 (2.21%)  3 2/139 (1.44%)  2
Fall  [1]  4/136 (2.94%)  5 0/139 (0.00%)  0
Seroma  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Spinal fracture  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Dermatitis radiation  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Burn  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Wrist fracture  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Wound dehiscence  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Radiation recall reaction  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Investigations     
White blood cell decreased  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Other, specify  [1]  2/136 (1.47%)  2 2/139 (1.44%)  2
White blood cell decreased  [1]  1/136 (0.74%)  2 6/139 (4.32%)  8
Ejection fraction decreased  [1]  4/136 (2.94%)  4 5/139 (3.60%)  5
Creatinine increased  [1]  1/136 (0.74%)  1 4/139 (2.88%)  5
Alanine aminotransferase increased  [1]  2/136 (1.47%)  3 3/139 (2.16%)  3
Weight gain  [1]  1/136 (0.74%)  1 4/139 (2.88%)  4
Neutrophil count decreased  [1]  0/136 (0.00%)  0 4/139 (2.88%)  5
Aspartate aminotransferase increased  [1]  3/136 (2.21%)  3 1/139 (0.72%)  1
Lymphocyte count decreased  [1]  0/136 (0.00%)  0 3/139 (2.16%)  3
Alkaline phosphatase increased  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Platelet count decreased  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Weight loss  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Chloesterol high  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Activated partial thromboplastin time prolonged  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Metabolism and nutrition disorders     
Hyperglycemia  [1]  3/136 (2.21%)  12 5/139 (3.60%)  6
Anorexia  [1]  3/136 (2.21%)  3 3/139 (2.16%)  3
Hypokalemia  [1]  3/136 (2.21%)  3 0/139 (0.00%)  0
Dehydration  [1]  2/136 (1.47%)  3 0/139 (0.00%)  0
Hyponatremia  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Hypocalcemia  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Hyperkalemia  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Hypercalcemia  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Musculoskeletal and connective tissue disorders     
Arthralgia  [2]  2/136 (1.47%)  2 3/139 (2.16%)  3
Myalgia  [2]  3/136 (2.21%)  5 8/139 (5.76%)  12
Other, specify  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Back pain  [2]  2/136 (1.47%)  7 2/139 (1.44%)  10
Bone pain  [2]  1/136 (0.74%)  1 2/139 (1.44%)  2
Pain in extremity  [2]  4/136 (2.94%)  4 6/139 (4.32%)  11
Neck pain  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Arthralgia  [1]  53/136 (38.97%)  103 41/139 (29.50%)  78
Myalgia  [1]  48/136 (35.29%)  91 39/139 (28.06%)  74
Other, specify  [1]  3/136 (2.21%)  4 2/139 (1.44%)  2
Back pain  [1]  38/136 (27.94%)  85 39/139 (28.06%)  58
Bone pain  [1]  22/136 (16.18%)  47 21/139 (15.11%)  47
Pain in extremity  [1]  12/136 (8.82%)  15 13/139 (9.35%)  16
Fracture  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Osteoporosis  [1]  2/136 (1.47%)  2 3/139 (2.16%)  5
Chest wall pain  [1]  0/136 (0.00%)  0 4/139 (2.88%)  4
Neck pain  [1]  3/136 (2.21%)  3 0/139 (0.00%)  0
Generalized muscle weakness  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Arthritis  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Superficial soft tissue fibrosis  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Osteonecrosis of jaw  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Myositis  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Muscle weakness lower limb  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Exostosis  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Other, specify  [1]  1/136 (0.74%)  1 1/139 (0.72%)  2
Nervous system disorders     
Headache  [2]  5/136 (3.68%)  5 4/139 (2.88%)  12
Neuropathy  [2]  1/136 (0.74%)  1 1/139 (0.72%)  1
Peripheral sensory neuropathy  [2]  1/136 (0.74%)  1 2/139 (1.44%)  2
Dysgeusia  [2]  1/136 (0.74%)  1 2/139 (1.44%)  2
Paresthesia  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Headache  [1]  57/136 (41.91%)  158 57/139 (41.01%)  146
Other, specify  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Dizziness  [1]  13/136 (9.56%)  15 17/139 (12.23%)  25
Neuropathy  [1]  3/136 (2.21%)  6 5/139 (3.60%)  8
Peripheral sensory neuropathy  [1]  7/136 (5.15%)  8 8/139 (5.76%)  8
Dysguesia  [1]  1/136 (0.74%)  1 2/139 (1.44%)  3
Neuralgia  [1]  3/136 (2.21%)  3 2/139 (1.44%)  2
Lethargy  [1]  0/136 (0.00%)  0 2/139 (1.44%)  5
Syncope  [1]  2/136 (1.47%)  2 2/139 (1.44%)  2
Peripheral motor neuropathy  [1]  1/136 (0.74%)  1 1/139 (0.72%)  2
Concentration impairment  [1]  0/136 (0.00%)  0 1/139 (0.72%)  2
Vasovagal reactions  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Trigeminal nerve disorder  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Somnolence  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Seizure  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Radiculitis  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Presyncope  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Paresthesia  [1]  0/136 (0.00%)  0 4/139 (2.88%)  5
Memory impairment  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Edema cerebral  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Depressed level of consciousness  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Psychiatric disorders     
Anxiety  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Other, specify  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Insomnia  [1]  11/136 (8.09%)  13 11/139 (7.91%)  11
Anxiety  [1]  4/136 (2.94%)  5 8/139 (5.76%)  8
Depression  [1]  7/136 (5.15%)  7 5/139 (3.60%)  5
Agitation  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Personality change  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Libido decreased  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Confusion  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Renal and urinary disorders     
Urinary tract infection  [1]  1/136 (0.74%)  1 3/139 (2.16%)  9
Cystitis noninfective  [1]  2/136 (1.47%)  3 1/139 (0.72%)  1
Urinary incontinence  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Urinary frequency  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Urinary urgency  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Hematuria  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Urinary tract pain  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Renal calculi  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Reproductive system and breast disorders     
Other, specify  [1]  1/136 (0.74%)  3 3/139 (2.16%)  3
Breast pain  [1]  5/136 (3.68%)  6 2/139 (1.44%)  2
Vaginal dryness  [1]  5/136 (3.68%)  6 1/139 (0.72%)  1
Vaginal hemorrhage  [1]  1/136 (0.74%)  3 0/139 (0.00%)  0
Vaginal discharge  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Pelvic pain  [1]  1/136 (0.74%)  1 1/139 (0.72%)  1
Vaginal inflammation  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Dyspareunia  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  [2]  0/136 (0.00%)  0 2/139 (1.44%)  2
Dyspnea  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Nasal congestion  [2]  2/136 (1.47%)  2 3/139 (2.16%)  5
Cough  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Sore throat  [2]  2/136 (1.47%)  2 2/139 (1.44%)  2
Epistaxis  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Breast pain  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Other, specify  [1]  4/136 (2.94%)  4 4/139 (2.88%)  4
Allergic Rhinitis  [1]  14/136 (10.29%)  19 14/139 (10.07%)  19
Dyspnea  [1]  15/136 (11.03%)  15 18/139 (12.95%)  21
Nasal congestion  [1]  11/136 (8.09%)  13 12/139 (8.63%)  13
Cough  [1]  12/136 (8.82%)  13 15/139 (10.79%)  16
Sore throat  [1]  2/136 (1.47%)  2 5/139 (3.60%)  8
Epistaxis  [1]  5/136 (3.68%)  6 4/139 (2.88%)  5
Laryngeal inflammation  [1]  3/136 (2.21%)  3 0/139 (0.00%)  0
Sleep apnea  [1]  0/136 (0.00%)  0 2/139 (1.44%)  2
Postnasal drip  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Sinus disorder  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Pneumonitis  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Pleuritic pain  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Laryngeal obstruction  [1]  3/136 (2.21%)  3 0/139 (0.00%)  0
Hypoxia  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Bronchospasm  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Skin and subcutaneous tissue disorders     
Pruritus  [2]  95/136 (69.85%)  429 89/139 (64.03%)  371
Skin induration  [2]  81/136 (59.56%)  337 67/139 (48.20%)  244
Other, specify  [2]  9/136 (6.62%)  13 10/139 (7.19%)  21
Rash maculo-papular  [2]  1/136 (0.74%)  1 3/139 (2.16%)  11
Rash acneiform  [2]  0/136 (0.00%)  0 1/139 (0.72%)  4
Nail loss  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Bullous dermatitis  [2]  2/136 (1.47%)  2 0/139 (0.00%)  0
Pruritus  [1]  5/136 (3.68%)  5 10/139 (7.19%)  12
Other, specify  [1]  14/136 (10.29%)  17 10/139 (7.19%)  12
Rash maculo-papular  [1]  6/136 (4.41%)  6 2/139 (1.44%)  7
Rash acneiform  [1]  6/136 (4.41%)  9 4/139 (2.88%)  4
Urticaria  [1]  5/136 (3.68%)  6 2/139 (1.44%)  5
Dry skin  [1]  2/136 (1.47%)  2 2/139 (1.44%)  3
Nail loss  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Alopecia  [1]  1/136 (0.74%)  1 3/139 (2.16%)  3
Nail ridging  [1]  1/136 (0.74%)  1 2/139 (1.44%)  2
Skin hyperpigmentation  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Nail discoloration  [1]  0/136 (0.00%)  0 1/139 (0.72%)  1
Eythema multiforme  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Surgical and medical procedures     
Other, specify  [2]  4/136 (2.94%)  4 2/139 (1.44%)  2
Other, specify  [1]  4/136 (2.94%)  5 4/139 (2.88%)  4
Vascular disorders     
Hot flashes  [2]  2/136 (1.47%)  2 1/139 (0.72%)  1
Lymphedema  [2]  0/136 (0.00%)  0 1/139 (0.72%)  1
Hematoma  [2]  1/136 (0.74%)  1 0/139 (0.00%)  0
Hot flashes  [1]  16/136 (11.76%)  21 18/139 (12.95%)  21
Lymphedema  [1]  9/136 (6.62%)  10 7/139 (5.04%)  7
Hypertension  [1]  7/136 (5.15%)  8 7/139 (5.04%)  7
Thromboembolic event  [1]  2/136 (1.47%)  2 2/139 (1.44%)  2
Hematoma  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Flushing  [1]  2/136 (1.47%)  2 1/139 (0.72%)  1
Superficial thrombophlebitis  [1]  2/136 (1.47%)  2 0/139 (0.00%)  0
Peripheral ischemia  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Hypotension  [1]  1/136 (0.74%)  1 0/139 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Systemic
[2]
Local
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.
In the event a Study is a multi-center clinical study, Institution and Principal Investigator will refrain from any disclosure or publication of Study data until the earlier of: (i) the publication of a multi-center publication or (ii) eighteen months following the conclusion of the Study. Nothing in this Article 6 is intended to limit or restrict in any way Sponsor's right to publish independently any Study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Program Director, Karen Arrington, RN, BSN
Organization: Cancer Insight
Phone: 210-243-5711
EMail: karrington@cancerinsight.com
Layout table for additonal information
Responsible Party: George E. Peoples, Cancer Insight, LLC
ClinicalTrials.gov Identifier: NCT01570036    
Other Study ID Numbers: 368255
1137008 / 20130058 ( Other Identifier: Western Institutional Review Board )
First Submitted: March 25, 2012
First Posted: April 4, 2012
Results First Submitted: June 17, 2019
Results First Posted: December 2, 2020
Last Update Posted: December 2, 2020