A Phase II Study of Anti-CD3 x Anti-HER2/Neu (Her2Bi) Armed Activated T Cells (ATC) After Neoadjuvant Chemo in Pts.With HER2/Neu (0-2+)-Negative Stage II-III Breast Cancers
OBJECTIVES:
I. To determine, in a phase II clinical trial of women with stage II-III human epidermal
growth factor receptor (HER)2-negative breast cancer, if a regimen of neoadjuvant
chemotherapy (chemoT) followed by immunotherapy (IT) improves the complete pathologic
response (pCR) rate at the time of surgery. IT will consist of 4 infusions of 20 x 10^9
Her2Bi-armed activated T cells (ATC) (aATC) given once per week for 4 weeks. The association
between pCR and clinical responses (disease free survival [DFS] and overall survival [OS])
will be investigated.
II. To determine if aATC infusions following neoadjuvant chemoT will modulate the
cytotoxicity of lymphocytes in the blood and tumor infiltrating lymphocytes (TIL) and if
there is an association between systemic and tumor site anti-tumor responses. The immune
measures will be done pre-IT, prior to infusion #3 (midpoint of IT), 2 weeks after IT (prior
to surgery), and 1 month after surgery.
III. To determine if aATC infusions after neoadjuvant chemoT decreases the frequency and
colony forming ability of the putative breast cancer stem cells (CSC) in the tumor tissue at
the time of surgery, compared to those obtained in the tumor biopsy after chemoT. The
association between the observed changes in numbers and proportion of CD44^hi/CD24^lo,
CD133, aldehyde dehydrogenase activity (ALDH1) positive cells and the pCR will be
investigated.
OUTLINE:
NEOADJUVANT CHEMOTHERAPY: Patients receive dose-dense AC->T regimen comprising doxorubicin
hydrochloride intravenously (IV) and cyclophosphamide IV once every 2 weeks for 4 courses
followed by paclitaxel IV once every 2 weeks for 4 courses or paclitaxel IV once weekly for
12 weeks. Or, patients receive TAC regimen comprising docetaxel IV, doxorubicin
hydrochloride IV, and cyclophosphamide IV once every 3 weeks for 6 courses. Treatment
continues in the absence of disease progression or unacceptable toxicity.
IMMUNOTHERAPY: Beginning 3-6 days after the last dose of chemotherapy, patients receive
Her2Bi-armed activated T cells IV over 5-30 minutes once weekly for 4 weeks.
SURGERY: Patients then undergo surgical resection of the breast 2 weeks later.
After completion of study treatment, patients may be followed up at 1, 3, 6, and 12 months.
Interventional
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
pCR defined as absence of all invasive tumor in both breast and axilla
Estimated with as binomial proportion and 95% confidence interval. Estimates will be computed for both response-evaluable and for the entire study cohort. The association between measures of immune function using rank correlation methods will be estimated.
Up to 12 months post-surgery
No
Lawrence Lum
Principal Investigator
Barbara Ann Karmanos Cancer Institute
United States: Food and Drug Administration
2010-056
NCT01658969
July 2010
November 2015
Name | Location |
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Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |