Laboratory-Treated T Cells After Second-Line Chemotherapy in Treating Women With HER2/Neu-Negative Metastatic Breast Cancer

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentClosed18 and overNCI, OtherCDR0000657998
P30CA022453, WSU-2009-085, 2009-085, NCT01022138

Trial Description


RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Treating a patient's T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Giving laboratory-treated T cells after chemotherapy may be an effective treatment for breast cancer.

PURPOSE: This phase II trial is studying how well giving laboratory-treated T cells after second-line chemotherapy works in treating women with HER2/neu-negative metastatic breast cancer.

Further Study Information


  • To determine in a phase II trial whether Her2Bi armed ATC infused after ChemoT for patients with HER2 0-2+ MBC or locally advanced, unresectable breast cancer would improve median PFS by 2 months beyond the median PFS of 2 months estimated from published trials in a one stage design.
  • To determine the overall survival (OS) of patients with HER2 0-2+ MBC and locally advanced, unresectable breast cancer who receive aATC infusion after ChemoT.
  • To confirm the toxicity profile for Her2Bi armed ATC given after ChemoT for patients with HER2 0-2+ MBC.
  • To measure functional and phenotypic changes in immune cell populations (blood and tumor sites, if accessible) as a consequence of armed ATC (tumor biopsies done at KCI only). Cytokine responses, phenotypic markers of differentiation, and anti-tumor cytotoxicity will be examined.
  • OUTLINE: Patients receive second-line chemotherapy for 4 courses or 4 months. Beginning as early as 1.5 weeks and as late as 4 weeks after chemotherapy, the patients will receive the first infusion of anti-CD3 x anti-HER2/neu bispecific antibody-armed activated T-cells (ATC) IV over 30-60 minutes once a week for 3 weeks. Low dose granulocyte-macrophage colony stimulating factor (250 µg/m2/twice per week) will start 3 days before the first aATC infusion and end with the last dose of aATC. Patients who are already on the protocol will be given a choice to add GM-CSF to their treatment regimen (after reconsenting) or continue to their treatment without GM-CSF. Patients then receive a boost of anti-CD3 x anti-HER2/neu bispecific antibody-armed ATC at 12 weeks after the 3rd ATC infusion.

Blood and tumor tissue samples may be collected periodically for biomarker and other analyses.

After completion of study therapy, patients are followed up periodically for ≥ 2 years.

Eligibility Criteria


  • Histologically or cytologically confirmed metastatic breast cancer
  • All histological types allowed
  • Recurrent disease after first-line chemotherapy in the metastatic setting, as defined by 1 of the following:
  • No objective response after administration of ≥ 4 courses of first-line chemotherapy
  • Progression while receiving first-line chemotherapy without experiencing any transient improvement
  • Brief objective response to first-line chemotherapy with subsequent progression while receiving the same therapy or within 12 months after the last dose of therapy
  • Patients who just started second line chemotherapy within 1 month allowed provided there is no documented progressive disease on the second line chemotherapy
  • HER2/neu-negative disease, defined as 0-2+ by IHC and/or FISH ratio (HER2 gene signals to chromosome 17 signals) ≤ 2.2
  • No HER2 overexpression by IHC or overamplification by FISH, as defined by any of the following:
  • 3+ IHC (uniform, intense membrane staining of > 30% of invasive tumor cells)
  • FISH result of > 6 HER2 gene copies per nucleus
  • FISH ratio > 2.2
  • Measurable or evaluable metastatic disease as documented by radiograph, CT scan, PET/CT scan, MRI, bone scan, or physical exam
  • At least 1 bidimensionally measurable lesion (that has not been irradiated) with a minimum size in at least one diameter of ≥ 20 mm for liver lesions and ≥ 10 mm for lung, skin, and lymph node metastases
  • Biopsy of recurrent site(s) is not required
  • No clinical evidence of active CNS metastases
  • Patients with treated brain metastases (i.e., those who have received definitive radiotherapy, chemotherapy, and/or surgical resection) are eligible
  • Hormone receptor status not specified


  • Menopausal status not specified
  • Karnofsky performance status 70-100%
  • Life expectancy ≥ 3 months
  • Granulocytes ≥ 1,000/mm³
  • Platelet count ≥ 50,000/mm³
  • Hemoglobin ≥ 8 g/dL
  • BUN ≤ 1.5 times normal
  • Serum creatinine < 1.8 mg/dL
  • Creatinine clearance ≥ 60 mL/min
  • Bilirubin < 1.5 times normal
  • ALT and AST < 5 times upper limit of normal (ULN)
  • Alkaline phosphatase < 5 times ULN
  • LVEF ≥ 45% at rest by MUGA or ECHO
  • FEV_1, DLCO, and FVC ≥ 50% of predicted
  • Negative pregnancy test
  • No HIV positivity
  • No myocardial infarction within the past year
  • No current coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO)
  • No clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA/ECHO results)
  • Patients whose systolic BP is consistently ≥ 140 mm Hg or diastolic BP is consistently ≥ 80 mm Hg are eligible provided their BP is controlled by antihypertensive medications for ≥ 7 days before the first activated T-cell infusion
  • No other malignancy within the past 5 years except for basal cell skin carcinoma and carcinoma in situ of the cervix
  • No serious medical or psychiatric illness that would preclude informed consent or intensive treatment


  • See Disease Characteristics
  • No more than 3 prior chemotherapy regimen for metastatic disease
  • Prior taxanes, anthracyclines, or any other chemotherapy allowed
  • No hormonal therapy within 2 weeks before leukapheresis
  • No radiotherapy to the axial skeleton within 4 weeks before leukapheresis
  • No concurrent steroids except those administered for adrenal failure, septic shock, or pulmonary toxicity or hormones administered for nondisease-related conditions (e.g., insulin for diabetes)

Trial Contact Information

Trial Lead Organizations/Sponsors

Barbara Ann Karmanos Cancer Institute

  • National Cancer Institute
Lawrence Lum, M.D., Principal Investigator

Link to the current record.
NLM Identifier NCT01022138 processed this data on March 25, 2015

Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to