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

• Status: Unknown status
• Trial end date: 2018-01-01
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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)