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

Phase 2

Terminated

Conditions: Breast Cancer

Interventions: Biological: HER2Bi-armed activated T cells
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Other: laboratory biomarker analysis
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery

Registration Number: NCT01147016

Lead Sponsor: Barbara Ann Karmanos Cancer Institute

Brief 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy	HER2Bi-armed activated T cells	HER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.
HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy	cyclophosphamide	HER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.
HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy	therapeutic conventional surgery	HER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.
HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy	neoadjuvant therapy	HER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.
HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy	laboratory biomarker analysis	HER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.
HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy	doxorubicin hydrochloride	HER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.
HER2Bi-armed activated T cells + Neoadjuvant Chemotherapy	paclitaxel	HER2Bi-armed activated T cells - Total of 4 of the T cell infusions IV over a period of 1 month Cyclophosphamide, doxorubicin hydrochloride, paclitaxel -As prescribed by physician, standard of care.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 years..	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion

Secondary Outcome Measures

Name	Time	Method
Overall Deaths	From date of randomization until date of death from any cause or end of study, whichever came first, assessed up to 7 years	Total number of deaths