Clinical trial NCT02061332: DC Vaccine for Patients With Ductal Carcinoma In Situ
Official title: A Randomized Trial of HER-2/Neu Pulsed DC1 Vaccine for Patients With DCIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
DCIS
Keywords: Breast Cancer
DCIS
Immunotherapy
Vaccine
Dendritic Cell
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2014-02-12
Enrollment: 58
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Women who are diagnosed with Her-2/neu over-expressing DCIS will receive DC1 vaccines by intranodal, intralesional, or both routes of administration. The primary objective will be safety and administration with secondary objectives of immune activation and clinical response.

Detailed description: The treatment of patients with DCIS can be individualized and tailored to the type of DCIS and the relative risk of the lesion. HER-2/neu over-expressing DCIS represents a group of patients with significant risk for development of invasive breast cancer. In this proposal we will continue to evaluate the development of type I polarized DC for the treatment of DCIS by evaluating whether further improvements in therapeutic response can be achieved by intratumoral administration of HER-2/neu pulsed DC1 compared with our current intranodal administration. Women who are diagnosed with Her-2/neu over-expressing DCIS with no invasive carcinoma will be eligible for this study. Patients will receive DC1 vaccines by intranodal, intralesional, or both routes of administration. The primary objective will be safety and administration with secondary objectives of immune activation and clinical response. We will also develop a novel assay to monitor ongoing immunity to HER-2/neu, and lastly will begin to develop these vaccines for patients with invasive breast cancer as well. Fifty-four subjects will be randomized to one of three treatment arms: intranodal injection, intralesional injection, or intranodal and intralesional injection of the vaccine. Upon entering this study, the subjects' blood will be drawn in a way that collects only the white blood cells. Subjects then receive six vaccines over a six week period. They will then undergo the standard surgical procedure to remove any remaining DCIS in the breast.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years.
* Subjects with biopsy-proven DCIS, DCIS with microinvasion, DCIS with invasive disease under 5 mm, or Paget's Disease of the nipple (DCIS of the nipple) who have not yet received definitive treatment.
* HER-2/neu positive tumor as determined by \>5% of tumor population expressing this marker by immunohistochemical staining 2+ using anti-HER-2/neu verified by Dr. Paul Zhang in the Department of Pathology.
* Women of childbearing age with a negative pregnancy test documented prior to enrollment.
* Subjects with ECOG Performance Status Score of 0 or 1 (Appendix D).
* Subjects willing to use birth control if necessary
* Subjects who 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 females (pregnancy testing to be performed within 7 days prior to administration of first dose of vaccine).
* Subjects who have had a complete excisional biopsy of their tumor.
* Subjects with suspicion of invasive disease \> 5mm by MRI performed within 2 months of study recruitment.
* Screen and exclude subjects with positive HIV or hepatitis C at baseline.
* Subjects with coagulopathies, including thrombocytopenia with platelet count \<75,000, INR \> 1.5 and partial thromboplastin time \> 50 sec
* Subjects with major cardiac illness MUGA \< 50% EF.
* Subjects with pre-existing medical illnesses or medications which might interfere with the study.
* Subjects with laboratory tests reflecting ¬\> grade 1 toxicity by NCI CTC version 3.0 including CBC, liver function tests, urinalysis, EKG if cannot be corrected on repeat test in 7 days.

Primary outcomes:
measure: Blood Pressure
timeFrame: up to 60 minutes post vaccine
measure: Temperature
timeFrame: up to 60 minutes post vaccine
measure: Pulse
timeFrame: up to 60 minutes post vaccine
Secondary outcomes:
measure: Immune Response
timeFrame: 6-8 weeks
measure: Mammogram
timeFrame: 6-8 weeks
measure: MRI
timeFrame: 6-8 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Brian J 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.