Clinical trial NCT02063724: HER-2 Pulsed DC Vaccine to Prevent Recurrence of Invasive Breast Cancer
Official title: Pilot Phase I HER-2 Pulsed DC Vaccine to Prevent Recurrence for Patients With HER-2 Driven High Risk Invasive Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: Invasive Breast Cancer
Breast Cancer
Immunotherapy
Vaccine
Dendritic Cell
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Abramson Cancer Center at Penn Medicine
First posted: 2014-02-14
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Rate of Treatment Regimen Completion
timeFrame: 12 months
Secondary outcomes:
measure: Immune Response
timeFrame: 12 months
measure: Occurrence of Treatment Related Adverse Events
timeFrame: 2 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Brian Czerniecki, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Czerniecki BJ, Roses RE, Koski GK. Development of vaccines for high-risk ductal carcinoma in situ of the breast. Cancer Res. 2007 Jul 15;67(14):6531-4. doi: 10.1158/0008-5472.CAN-07-0878.
citation: Czerniecki BJ, Koski GK, Koldovsky U, Xu S, Cohen PA, Mick R, Nisenbaum H, Pasha T, Xu M, Fox KR, Weinstein S, Orel SG, Vonderheide R, Coukos G, DeMichele A, Araujo L, Spitz FR, Rosen M, Levine BL, June C, Zhang PJ. Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res. 2007 Feb 15;67(4):1842-52. doi: 10.1158/0008-5472.CAN-06-4038. Epub 2007 Feb 9.
citation: Koski GK, Koldovsky U, Xu S, Mick R, Sharma A, Fitzpatrick E, Weinstein S, Nisenbaum H, Levine BL, Fox K, Zhang P, Czerniecki BJ. A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunother. 2012 Jan;35(1):54-65. doi: 10.1097/CJI.0b013e318235f512.
citation: Sharma A, Koldovsky U, Xu S, Mick R, Roses R, Fitzpatrick E, Weinstein S, Nisenbaum H, Levine BL, Fox K, Zhang P, Koski G, Czerniecki BJ. HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ. Cancer. 2012 Sep 1;118(17):4354-62. doi: 10.1002/cncr.26734. Epub 2012 Jan 17.