Breast Cancer
Conditions
Keywords
Invasive Breast Cancer, Breast Cancer, Immunotherapy, Vaccine, Dendritic Cell
Brief summary
The purpose of this study is to determine the safety and immunogenicity of HER-2 pulsed DC1 vaccine in high risk HER-2 high and intermediate expression breast cancers. Participants will have HER-2 driven IBC at least Stage IIIA with N2 following chemotherapy with/without trastuzumab or recurrence exclusive of new primary tumor but rendered NED. Mammogram, laboratory studies, CT, and leukapheresis will be performed, in addition to vaccine administration.
Detailed description
Dendritic cell cancer vaccines combined with chemotherapy may increase complete responses giving breast cancer specific immune cells greater opportunity to function while the immune repertoire is being shifted by chemotherapy to anti-breast cancer response and offer the chance to test secondary prevention of breast cancer in high risk settings. Participants with HER-2 driven IBC at least Stage IIIA with N2 (4 positive nodes) following chemotherapy with or without trastuzumab or those with recurrence exclusive of new primary tumor but rendered NED will be undergo mammograms, laboratory studies, and leukapheresis. Vaccines will be manufactured using participants' leukapheresis product, which will be administered in the Clinical Research Center 1 Dulles Building weekly for 6 weeks. Three booster vaccines will be administered at 3 month intervals following the initial induction vaccines. Immune analysis will be done after participant receives all induction vaccines and again after they receive all booster vaccines. This study began at the Abramson Cancer Center of the University of Pennsylvania and will be continued at H. Lee Moffitt Cancer Center and Research Institute.
Interventions
BIOLOGICALHER-2 pulsed Dendritic Cell Vaccine
6 weekly HER-2 pulsed dendritic cell vaccines followed by 3 booster vaccines once every 3 months. Each dose will consist of between 1.0-2.0 x 10\^7 cells and will be injected into 1-2 different normal groin lymph nodes or axillary nodes.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women over Age 18 years. * Potential participants with Invasive Breast Cancer at least Stage IIIA, greater than or equal to N2 (\>4 positive nodes) or have recurrent metastatic breast cancer rendered NED by any means that are classic HER-2 3+ 30%, 2+ IHC and FISH positive or HER-2 2+ FISH negative, that have completed chemotherapy and/or trastuzumab and are within 1 year from their last treatment and have no evidence of disease. * Deemed to require anti-estrogen therapy for treatment of their breast cancer can continue anti-estrogen therapy during vaccinations. * Women of childbearing age with a negative pregnancy test documented prior to enrollment. * Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or 1. * Willing to use birth control if necessary. * Have voluntarily signed a written Informed Consent in accordance with institutional policies after its contents have been fully explained to them.
Exclusion criteria
* Pregnant or lactating. * Positive for positive HIV or hepatitis C at baseline. * Patients with coagulopathies, including thrombocytopenia with platelet count less than 75,000, INR greater than 1.5 and partial thromboplastin time greater than 50 sec. * Major cardiac illness MUGA less than 50% EF. * Pre-existing medical illnesses or medications which might interfere with the study as determined by Principal Investigator (PI).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Treatment Regimen Completion | 12 months | Number of participants willing and able to complete treatment regimen, to address feasibility. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Response | 12 months | Number of participants with immune response. Participants will undergo leukapheresis after completion of 6 vaccines and 3 boost vaccines for the purpose of obtaining lymphocytes and monocytes for in vitro immunologic testing. |
| Occurrence of Treatment Related Adverse Events | 2 years | Adverse Events reported as Related to Study Treatment, per adverse event category. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBrian Czerniecki, M.D., Ph.D.
H. Lee Moffitt Cancer Center and Research Institute
Participant flow
Recruitment details
Participants were enrolled October 2014 through June 2017 at Abramson Cancer Center of the University of Pennsylvania and Moffitt Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| HER-2 Pulsed Dendritic Cell Vaccine 6 weekly HER-2 pulsed dendritic cell vaccines followed by 3 booster vaccines once every 3 months. Each dose will consist of between 1.0-2.0 x 10\^7 cells and will be injected into 1-2 different normal groin lymph nodes or axillary nodes.
HER-2 pulsed Dendritic Cell Vaccine: 6 weekly HER-2 pulsed dendritic cell vaccines followed by 3 booster vaccines once every 3 months. Each dose will consist of between 1.0-2.0 x 10\^7 cells and will be injected into 1-2 different normal groin lymph nodes or axillary nodes. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | HER-2 Pulsed Dendritic Cell Vaccine |
|---|---|
| Age, Continuous | 52 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 10 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Rate of Treatment Regimen Completion
Number of participants willing and able to complete treatment regimen, to address feasibility.
Time frame: 12 months
Population: All participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HER-2 Pulsed Dendritic Cell Vaccine | Rate of Treatment Regimen Completion | 14 Participants |
Secondary
Immune Response
Number of participants with immune response. Participants will undergo leukapheresis after completion of 6 vaccines and 3 boost vaccines for the purpose of obtaining lymphocytes and monocytes for in vitro immunologic testing.
Time frame: 12 months
Population: All participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HER-2 Pulsed Dendritic Cell Vaccine | Immune Response | 15 Participants |
Secondary
Occurrence of Treatment Related Adverse Events
Adverse Events reported as Related to Study Treatment, per adverse event category.
Time frame: 2 years
Population: All participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Allergic reaction to pheresis | 1 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Tingling with pheresis | 1 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Fatigue | 1 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Chills | 2 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Bruising at site of injection | 1 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Lips and finger numbness and tingling | 1 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Rash | 1 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Citrate toxicity | 2 Participants |
| HER-2 Pulsed Dendritic Cell Vaccine | Occurrence of Treatment Related Adverse Events | Fever | 2 Participants |