DC Vaccine for Patients With Ductal Carcinoma In Situ

Breast Cancer Clinical Trial

— DCIS6  

Official title:

A Randomized Trial of HER-2/Neu Pulsed DC1 Vaccine for Patients With DCIS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02061332
• Other study ID #: 807010
• Secondary ID: 15107
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2009
• Est. completion date: October 7, 2015

Study information

• Verified date: April 2020
• Source: Abramson Cancer Center of the University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00923143

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: October 7, 2015
• Est. primary completion date: August 8, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• DCIS

Intervention

Biological:
• HER-2 Pulsed Dendritic cell Vaccine
6 weekly HER-2 pulsed dendritic cell vaccines will be administered to subjects in each of the 3 arms.

Locations

Country	Name	City	State
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abramson Cancer Center of the University of Pennsylvania

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Epub 2007 Feb 9. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Pressure	Blood pressure will be obtained just prior to the vaccination then, every 15 minutes for the first hour after the dose is given.	up to 60 minutes post vaccine
Primary	Temperature	Temperature will be obtained just prior to the vaccination then, every 15 minutes for the first hour after the dose is given.	up to 60 minutes post vaccine
Primary	Pulse	Pulse will be obtained just prior to the vaccination then, every 15 minutes for the first hour after the dose is given.	up to 60 minutes post vaccine
Secondary	Immune Response	Subjects 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.	6-8 weeks
Secondary	Mammogram	All subjects will have a post-vaccine bilateral mammogram to evaluate response to vaccination. Mammograms will be performed within two weeks after the 6th vaccination.	6-8 weeks
Secondary	MRI	All subjects will have a post-vaccine bilateral breast MRI to evaluate response to vaccination. MRIs will be performed within two weeks after the 6th vaccination.	6-8 weeks