Trial Outcomes & Findings for Combination Immunotherapy With Herceptin and the HER2 Vaccine NeuVax (NCT NCT01570036)

Last Updated: 2020-12-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

275 participants

Primary outcome timeframe

Disease-free survival at 24 months

Results posted on

2020-12-02

Participant Flow

Participant milestones

Participant milestones
Measure	Herceptin + NeuVax Vaccine 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.	Herceptin + GM-CSF Only 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 Study STARTED	136	139
Overall Study Primary Vaccine Series Completed	121	132
Overall Study Booster Series Completed	40	30
Overall Study COMPLETED	18	17
Overall Study NOT COMPLETED	118	122

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Only evaluable for patients that underwent breast conservation therapy.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Herceptin + NeuVax Vaccine n=136 Participants 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.	Herceptin + GM-CSF Only n=139 Participants 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 n=275 Participants Total of all reporting groups
Age, Continuous	52.2 years n=136 Participants	50.5 years n=139 Participants	51.6 years n=275 Participants
Sex: Female, Male Female	136 Participants n=136 Participants	139 Participants n=139 Participants	275 Participants n=275 Participants
Sex: Female, Male Male	0 Participants n=136 Participants	0 Participants n=139 Participants	0 Participants n=275 Participants
Race/Ethnicity, Customized White	109 Participants n=136 Participants	97 Participants n=139 Participants	206 Participants n=275 Participants
Race/Ethnicity, Customized Asian	2 Participants n=136 Participants	9 Participants n=139 Participants	11 Participants n=275 Participants
Race/Ethnicity, Customized Black	13 Participants n=136 Participants	20 Participants n=139 Participants	33 Participants n=275 Participants
Race/Ethnicity, Customized Hispanic	10 Participants n=136 Participants	9 Participants n=139 Participants	19 Participants n=275 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=136 Participants	4 Participants n=139 Participants	6 Participants n=275 Participants
Nottingham modified, Scarff-Bloom-Richardson Grade Grade 1	8 Participants n=136 Participants	14 Participants n=139 Participants	22 Participants n=275 Participants
Nottingham modified, Scarff-Bloom-Richardson Grade Grade 2	57 Participants n=136 Participants	56 Participants n=139 Participants	113 Participants n=275 Participants
Nottingham modified, Scarff-Bloom-Richardson Grade Grade 3	69 Participants n=136 Participants	69 Participants n=139 Participants	138 Participants n=275 Participants
Hormone receptor status ER Positive	81 Participants n=136 Participants	95 Participants n=139 Participants	176 Participants n=275 Participants
Hormone receptor status PR Positive	77 Participants n=136 Participants	83 Participants n=139 Participants	160 Participants n=275 Participants
Hormone receptor status Triple Negative	53 Participants n=136 Participants	44 Participants n=139 Participants	97 Participants n=275 Participants
HER2 Immunohistochemistry (IHC) IHC 1+	89 Participants n=136 Participants	89 Participants n=139 Participants	178 Participants n=275 Participants
HER2 Immunohistochemistry (IHC) IHC 2+	47 Participants n=136 Participants	50 Participants n=139 Participants	97 Participants n=275 Participants
Breast surgery Breast Conservation Therapy	39 Participants n=136 Participants	34 Participants n=139 Participants	73 Participants n=275 Participants
Breast surgery Mastectomy	97 Participants n=136 Participants	104 Participants n=139 Participants	201 Participants n=275 Participants
Breast surgery None	0 Participants n=136 Participants	1 Participants n=139 Participants	1 Participants n=275 Participants
Chemotherapy Neoadjuvant	72 Participants n=136 Participants	76 Participants n=139 Participants	148 Participants n=275 Participants
Chemotherapy Adjuvant	59 Participants n=136 Participants	57 Participants n=139 Participants	116 Participants n=275 Participants
Chemotherapy None	5 Participants n=136 Participants	6 Participants n=139 Participants	11 Participants n=275 Participants
Radiation with Breast Conservation Therapy Adjuvant	39 Participants n=39 Participants • Only evaluable for patients that underwent breast conservation therapy.	34 Participants n=34 Participants • Only evaluable for patients that underwent breast conservation therapy.	73 Participants n=73 Participants • Only evaluable for patients that underwent breast conservation therapy.
Radiation with Breast Conservation Therapy None	0 Participants n=39 Participants • Only evaluable for patients that underwent breast conservation therapy.	0 Participants n=34 Participants • Only evaluable for patients that underwent breast conservation therapy.	0 Participants n=73 Participants • Only evaluable for patients that underwent breast conservation therapy.
Radiation with Mastectomy Adjuvant	76 Participants n=97 Participants • Only evaluable for patients that underwent mastectomy.	89 Participants n=104 Participants • Only evaluable for patients that underwent mastectomy.	165 Participants n=201 Participants • Only evaluable for patients that underwent mastectomy.
Radiation with Mastectomy Neoadjuvant	2 Participants n=97 Participants • Only evaluable for patients that underwent mastectomy.	0 Participants n=104 Participants • Only evaluable for patients that underwent mastectomy.	2 Participants n=201 Participants • Only evaluable for patients that underwent mastectomy.
Radiation with Mastectomy None	19 Participants n=97 Participants • Only evaluable for patients that underwent mastectomy.	15 Participants n=104 Participants • Only evaluable for patients that underwent mastectomy.	34 Participants n=201 Participants • Only evaluable for patients that underwent mastectomy.
Axillary Surgery Axillary Dissection	81 Participants n=136 Participants	88 Participants n=139 Participants	169 Participants n=275 Participants
Axillary Surgery Sentinel Lymph Node Biopsy	55 Participants n=136 Participants	48 Participants n=139 Participants	103 Participants n=275 Participants
Axillary Surgery None	0 Participants n=136 Participants	3 Participants n=139 Participants	3 Participants n=275 Participants
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) Unknown	1 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	2 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	3 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) 0	0 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	1 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	1 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) I	4 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	3 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	7 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) IIA	16 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	13 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	29 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) IIB	19 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	18 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	37 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) IIIA	14 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	25 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	39 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) IIIB	7 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	2 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	9 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) IIIC	10 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	13 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	23 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Clinical Stage (for patients receiving neoadjuvant chemotherapy) IV*	1 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	0 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	1 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) Unknown	1 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	0 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	1 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) 0	5 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	4 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	9 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) I	11 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	9 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	20 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) IIA	16 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	15 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	31 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) IIB	12 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	11 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	23 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) IIIA	11 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	20 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	31 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) IIIB	4 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	3 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	7 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage (for patients receiving neoadjuvant chemotherapy) IIIC	12 Participants n=72 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	14 Participants n=76 Participants • Only neoadjuvant chemotherapy patients included into this patient count.	26 Participants n=148 Participants • Only neoadjuvant chemotherapy patients included into this patient count.
AJCC, 7th Edition, Pathologic Stage I	10 Participants n=64 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	9 Participants n=63 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	19 Participants n=127 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).
AJCC, 7th Edition, Pathologic Stage IIA	11 Participants n=64 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	12 Participants n=63 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	23 Participants n=127 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).
AJCC, 7th Edition, Pathologic Stage IIB	14 Participants n=64 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	14 Participants n=63 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	28 Participants n=127 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).
AJCC, 7th Edition, Pathologic Stage IIIA	21 Participants n=64 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	18 Participants n=63 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	39 Participants n=127 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).
AJCC, 7th Edition, Pathologic Stage IIIB	0 Participants n=64 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	0 Participants n=63 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	0 Participants n=127 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).
AJCC, 7th Edition, Pathologic Stage IIIC	8 Participants n=64 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	10 Participants n=63 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).	18 Participants n=127 Participants • The analysis only includes patients that did not receive neoadjuvant chemotherapy (thus, adjuvant and none).

PRIMARY outcome

Timeframe: Disease-free survival at 24 months

Outcome measures

Outcome measures
Measure	Herceptin + NeuVax Vaccine n=136 Participants 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.	Herceptin + GM-CSF Only n=139 Participants 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.
Disease-free Survival (DFS)	89.8 Percentage of participants who survived	83.8 Percentage of participants who survived

PRIMARY outcome

Timeframe: Disease-free survival up to 36 months

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.

Outcome measures

Outcome measures
Measure	Herceptin + NeuVax Vaccine n=136 Participants 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.	Herceptin + GM-CSF Only n=139 Participants 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.
Disease-free Survival (DFS)	86.7 Percent Survival	80.8 Percent Survival

SECONDARY outcome

Timeframe: 24 months

Population: The analysis was performed on those patients with data at each specified time point.

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.

Outcome measures

Outcome measures
Measure	Herceptin + NeuVax Vaccine n=136 Participants 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.	Herceptin + GM-CSF Only n=137 Participants 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.
Percent Ejection Fraction - A Measure of Cardiac Toxicity Baseline	60.82 Percent Ejection Fraction Standard Error .61	61.47 Percent Ejection Fraction Standard Error .47
Percent Ejection Fraction - A Measure of Cardiac Toxicity 3 Months	59.49 Percent Ejection Fraction Standard Error .54	59.56 Percent Ejection Fraction Standard Error .54
Percent Ejection Fraction - A Measure of Cardiac Toxicity 6 Months	59.92 Percent Ejection Fraction Standard Error .88	60.07 Percent Ejection Fraction Standard Error .57
Percent Ejection Fraction - A Measure of Cardiac Toxicity 12 Months	59.39 Percent Ejection Fraction Standard Error .56	59.7 Percent Ejection Fraction Standard Error .57
Percent Ejection Fraction - A Measure of Cardiac Toxicity 24 Months	61.05 Percent Ejection Fraction Standard Error .79	61.09 Percent Ejection Fraction Standard Error .78

SECONDARY outcome

Timeframe: Duration of vaccine or inoculation series and booster series, an average of 30 months.

Population: The safety analysis was performed only on patients that received NeuVax or Control.

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.

Outcome measures

Outcome measures
Measure	Herceptin + NeuVax Vaccine n=129 Participants 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.	Herceptin + GM-CSF Only n=132 Participants 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.
Local and Systemic Toxicities Local Grade 1	82.3 Percent Experiencing	55.7 Percent Experiencing
Local and Systemic Toxicities Local Grade 2	15.0 Percent Experiencing	33.0 Percent Experiencing
Local and Systemic Toxicities Local Grade 3	2.7 Percent Experiencing	11.3 Percent Experiencing
Local and Systemic Toxicities Systemic Grade 1	79.6 Percent Experiencing	58.5 Percent Experiencing
Local and Systemic Toxicities Systemic Grade 2	20.4 Percent Experiencing	30.2 Percent Experiencing
Local and Systemic Toxicities Systemic Grade 3	0 Percent Experiencing	11.3 Percent Experiencing

Adverse Events

Herceptin + NeuVax Vaccine

Serious events: 14 serious events

Other events: 136 other events

Deaths: 1 deaths

Herceptin + GM-CSF Only

Serious events: 12 serious events

Other events: 139 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Program Director, Karen Arrington, RN, BSN

Cancer Insight

Phone: 210-243-5711

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Herceptin + NeuVax Vaccine n=136 participants at risk 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.	Herceptin + GM-CSF Only n=139 participants at risk 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.
Infections and infestations Skin Infection	0.74% 1/136 • Number of events 2 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Blood and lymphatic system disorders Anemia	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Cardiac disorders Atrial fibrillation	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Cardiac disorders Heart failure	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 2 • The duration of the trial, up to 36 months.
Cardiac disorders Sinus tachycardia	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Gastrointestinal disorders Colonic hemorrhage	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Gastrointestinal disorders Esophageal obstruction	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Gastrointestinal disorders Pancreatitis	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
General disorders Fever	0.74% 1/136 • Number of events 2 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Hepatobiliary disorders Other, specify	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Immune system disorders Allergic reaction	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Infections and infestations Breast infection	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Infections and infestations Device related infection	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Infections and infestations Soft tissue infection	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Infections and infestations Wound infection	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Injury, poisoning and procedural complications Fracture	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Injury, poisoning and procedural complications Wound complication	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Investigations Creatinine increased	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Metabolism and nutrition disorders Hyperglycemia	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Other, specify	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Nervous system disorders Edema cerebral	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Nervous system disorders Seizure	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Nervous system disorders Syncope	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/136 • The duration of the trial, up to 36 months.	0.72% 1/139 • Number of events 1 • The duration of the trial, up to 36 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Respiratory, thoracic and mediastinal disorders Other, specify	0.74% 1/136 • Number of events 1 • The duration of the trial, up to 36 months.	0.00% 0/139 • The duration of the trial, up to 36 months.
Vascular disorders Thromboembolic event	1.5% 2/136 • Number of events 2 • The duration of the trial, up to 36 months.	1.4% 2/139 • Number of events 2 • The duration of the trial, up to 36 months.