NCT01147016

Targeted T Cells After Neoadjuvant Chemotherapy in Treating Women With Stage II or III Breast Cancer Undergoing Surgery

A Phase II Study of Anti-CD3 x Anti-HER2/Neu (Her2Bi) Armed Activated T Cells (ATC) After Neoadjuvant Chemotherapy in Women With HER2/Neu (0-2+), Hormone Receptor (HR) Negative Stage II-III Breast Cancers

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Barbara Ann Karmanos Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Neoadjuvant chemotherapy for women with stage II-III Her negative breast cancer followed by Her2Bi armed activated T cells (ATCs) may significantly improve the pathologic complete response (pCR) rate at the time of surgery. Arming ex vivo expanded T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Giving combination neoadjuvant chemotherapy followed by laboratory-treated T cells before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II clinical trial is studying how well giving laboratory-treated T cells after neoadjuvant chemotherapy works in treating women with stage II or stage III breast cancer undergoing surgery.

Detailed description

PRIMARY OBJECTIVES: I. To estimate progression-free survival (PFS) in women with stage II-III triple-negative breast cancer without a complete pathologic response (cPR) who receive a regimen of neoadjuvant chemotherapy (chemoT), surgery, and/or irradiation followed by 8 infusions of \~10-15 x 10\^9 Her2Bi-armed activated T cells (ATC) (aATC) given twice per week for 4 weeks in combination with IL-2 (aldesleukin) (300,000 IU/m\^2/day) and GM-CSF (sargramostim) (250 μg/m\^2/twice per week) beginning 3 days before the 1st infusion and ending 1 week after the last infusion (defined as immunotherapy). II. To estimate the change from baseline (pre immunotherapy \[IT\]) to post-IT in specific cytotoxicity and interferon gamma (IFN-γ) enzyme-linked immunosorbent spots (Elispots) of lymphocytes in the blood directed at breast cancer cells. III. To investigate if pathologic response and the changes in numbers and proportion of infiltrating cells and cancer stem cells in the tumor at the time of surgery are associated with progressive disease. 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 weeks after the last dose of chemotherapy, patients receive Her2Bi-armed activated T cells IV over 5-30 minutes twice weekly for 4 weeks. Patients also receive aldesleukin subcutaneously (SC) daily beginning 3 days before the first T cell infusion and ending 1 week after the last infusion. 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.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	HER2Bi-armed activated T cells	Total of 4 of the T cell infusions intravenously over a period of 1 month.
DRUG	cyclophosphamide	As prescribed by physician, standard of care.
DRUG	doxorubicin hydrochloride	As prescribed by physician, standard of care.
DRUG	paclitaxel	As prescribed by physician, standard of care.
OTHER	laboratory biomarker analysis	Immune studies will be done pre-immunotherapy, prior to the third infusion of activated T-cells, at the time of surgery, and 1 month after immunotherapy. If there are positive findings, additional optional studies will be done at 3, 6, and 12 months, if the immune studies show changes worthy of follow-up studies.
PROCEDURE	neoadjuvant therapy	As prescribed by physician, standard of care.
PROCEDURE	therapeutic conventional surgery	As recommended by physician, post immunotherapy.

Timeline

• Start date: 2010-07-01
• Primary completion: 2017-07-01
• Completion: 2017-07-26
• First posted: 2010-06-22
• Last updated: 2023-04-27
• Results posted: 2023-04-27

Locations

1 site across 1 country: United States