Trial Outcomes & Findings for Phase II Trial of Combination Immunotherapy With NeuVax and Trastuzumab in High-risk HER2+ Breast Cancer Patients (NCT NCT02297698)
NCT ID: NCT02297698
Last Updated: 2023-12-12
Results Overview
Compare invasive DFS between the two treatment groups from time of initiation of trastuzumab maintenance therapy (trasuzumab monotherapy) to time of invasive local, regional or distant recurrence, new primary, or death due to any cause. Disease state will be determined by the patients' own physicians at the individual study sites during their routine follow-up screening. This will occur for all enrolled patients, regardless of randomization, approximately 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 outcome measure of the trial is invasive DFS.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
100 participants
Primary outcome timeframe
Initiation of trastuzumab monotherapy through the end of the patient's fifth year of participation in the study.
Results posted on
2023-12-12
Participant Flow
Participant milestones
| Measure |
Trastuzumab + NeuVax
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations,
|
Trastuzumab + GM-CSF
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone. Upon completion of the primary vaccination series (PVS), booster inoculations (same dose and route) will be administered every six months x 4. The first booster inoculation will occur 6 months ± 2 weeks after the completion of the PVS, with subsequent boosters timed every six months + 2 weeks. Boosters will therefore occur at the following time points after completion of the PVS: 6 months ± 2 weeks, 12 months ± 2 weeks, 18 months ± 2 weeks and 24 months ± 2 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
50
|
|
Overall Study
COMPLETED
|
31
|
36
|
|
Overall Study
NOT COMPLETED
|
19
|
14
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase II Trial of Combination Immunotherapy With NeuVax and Trastuzumab in High-risk HER2+ Breast Cancer Patients
Baseline characteristics by cohort
| Measure |
Trastuzumab + NeuVax
n=50 Participants
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations,
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year,
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
Trastuzumab + GM-CSF
n=50 Participants
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone.
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy.
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
42 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Initiation of trastuzumab monotherapy through the end of the patient's fifth year of participation in the study.Compare invasive DFS between the two treatment groups from time of initiation of trastuzumab maintenance therapy (trasuzumab monotherapy) to time of invasive local, regional or distant recurrence, new primary, or death due to any cause. Disease state will be determined by the patients' own physicians at the individual study sites during their routine follow-up screening. This will occur for all enrolled patients, regardless of randomization, approximately 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 outcome measure of the trial is invasive DFS.
Outcome measures
| Measure |
Trastuzumab + NeuVax
n=50 Participants
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations,
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year,
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
Trastuzumab + GM-CSF
n=50 Participants
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone.
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy.
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
|---|---|---|
|
Invasive Disease-free Survival (DFS)
|
42 Participants
|
47 Participants
|
SECONDARY outcome
Timeframe: From the date of initiation of the vaccine or inoculation series and booster series up to 36 months.Standard local and systemic toxicities will be collected and graded per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 graded toxicity scale. For both the inoculations during the primary vaccine/inoculation series and the 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. Additionally, patients will return to their study site 48-72 hours after inoculation for questioning regarding any systemic toxicity and local injection site reactions. When they return to their study site, the local reaction at the inoculation sites will be examined and measured.
Outcome measures
| Measure |
Trastuzumab + NeuVax
n=50 Participants
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations,
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year,
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
Trastuzumab + GM-CSF
n=50 Participants
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone.
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy.
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
|---|---|---|
|
Local and Systemic Toxicities
|
46 Participants
|
43 Participants
|
SECONDARY outcome
Timeframe: From the date of the first inoculation of Trastuzumab monotherapy to the end of the patient's fifth year of participation in the study.Immune responses will be primarily documented using the delayed type hypersensitivity (DTH) reaction and using the dextramer assay to enumerate peptide-specific CTL. Each of these measurements will be performed regardless of randomization. DTH reactions will be measured prior to initiation of the primary vaccine/inoculation series, one month ± 1 week after completion of the primary vaccine/inoculation series, and one month ± 1 week after the final booster inoculation. Dextramer measurements will be performed prior to initiating the primary vaccine/inoculation series as well as one month ± 1 week after completion of the vaccine/inoculation series. Additionally, these assays may be performed pre- and post-each booster. Alternatively, these assayed time points may also be performed all at once on frozen and banked cells.
Outcome measures
| Measure |
Trastuzumab + NeuVax
n=50 Participants
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations,
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year,
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
Trastuzumab + GM-CSF
n=50 Participants
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone.
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy.
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
|---|---|---|
|
Evaluate in Vivo and in Vitro Immune Responses
|
5 Participants
|
5 Participants
|
Adverse Events
Trastuzumab + NeuVax
Serious events: 3 serious events
Other events: 43 other events
Deaths: 0 deaths
Trastuzumab + GM-CSF
Serious events: 5 serious events
Other events: 38 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Trastuzumab + NeuVax
n=50 participants at risk
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations,
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year,
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
Trastuzumab + GM-CSF
n=50 participants at risk
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone.
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy.
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
|---|---|---|
|
Infections and infestations
Left Breast Infection
|
2.0%
1/50 • Number of events 1 • 36 months
|
2.0%
1/50 • Number of events 1 • 36 months
|
|
General disorders
Fever
|
2.0%
1/50 • Number of events 1 • 36 months
|
2.0%
1/50 • Number of events 1 • 36 months
|
|
Pregnancy, puerperium and perinatal conditions
Unintended Pregnancy
|
0.00%
0/50 • 36 months
|
2.0%
1/50 • Number of events 1 • 36 months
|
|
Surgical and medical procedures
Procedural Complication-Tram Flap Failure
|
0.00%
0/50 • 36 months
|
2.0%
1/50 • Number of events 1 • 36 months
|
|
General disorders
Sepsis
|
2.0%
1/50 • Number of events 1 • 36 months
|
0.00%
0/50 • 36 months
|
|
Gastrointestinal disorders
UTI - Pyelonephritis
|
0.00%
0/50 • 36 months
|
2.0%
1/50 • Number of events 1 • 36 months
|
Other adverse events
| Measure |
Trastuzumab + NeuVax
n=50 participants at risk
Patients randomized to this arm will receive vaccinations of nelipepimut-S (1000 μg) and GM-CSF (250 μg) (NeuVax vaccine) administered intradermally every three weeks for six total vaccinations,
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year,
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
Trastuzumab + GM-CSF
n=50 participants at risk
Patients randomized to this arm will receive inoculations of GM-CSF (250 μg) administered in an identical manner to those receiving nelipepimut-S/GM-CSF (NeuVax). Patients will be blinded as to whether they are receiving nelipepimut-S/GM-CSF or GM-CSF alone.
Trastuzumab: Herceptin will be administered to patients every three weeks as monotherapy for one year, to be given upon completion of standard of care chemotherapy/radiotherapy.
GM-CSF: For patients randomized to the GM-CSF alone arm, they will receive inoculations of GM-CSF (250mcg) administered intradermally every three weeks for six total vaccinations,
|
|---|---|---|
|
Infections and infestations
Pruritus
|
12.0%
6/50 • Number of events 6 • 36 months
|
8.0%
4/50 • Number of events 4 • 36 months
|
|
Skin and subcutaneous tissue disorders
Injection site reaction-Erythema
|
10.0%
5/50 • Number of events 5 • 36 months
|
8.0%
4/50 • Number of events 4 • 36 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
8.0%
4/50 • Number of events 4 • 36 months
|
14.0%
7/50 • Number of events 7 • 36 months
|
|
Nervous system disorders
Headache
|
12.0%
6/50 • Number of events 6 • 36 months
|
6.0%
3/50 • Number of events 3 • 36 months
|
|
General disorders
Fatigue
|
6.0%
3/50 • Number of events 3 • 36 months
|
10.0%
5/50 • Number of events 5 • 36 months
|
|
Skin and subcutaneous tissue disorders
Pain Injection Site
|
8.0%
4/50 • Number of events 4 • 36 months
|
6.0%
3/50 • Number of events 3 • 36 months
|
|
General disorders
Fever
|
2.0%
1/50 • Number of events 1 • 36 months
|
4.0%
2/50 • Number of events 2 • 36 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.0%
3/50 • Number of events 3 • 36 months
|
0.00%
0/50 • 36 months
|
|
Gastrointestinal disorders
Diarrhea
|
2.0%
1/50 • Number of events 1 • 36 months
|
4.0%
2/50 • Number of events 2 • 36 months
|
|
Gastrointestinal disorders
Nausea
|
4.0%
2/50 • Number of events 2 • 36 months
|
0.00%
0/50 • 36 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/50 • 36 months
|
2.0%
1/50 • Number of events 1 • 36 months
|
|
General disorders
Chills
|
2.0%
1/50 • Number of events 1 • 36 months
|
0.00%
0/50 • 36 months
|
|
General disorders
Withdrawls
|
14.0%
7/50 • Number of events 7 • 36 months
|
14.0%
7/50 • Number of events 7 • 36 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place