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
- Signed and dated IRB-approved consent form
- Patients may be male or female.
- 18 years of age or older. Women of reproductive potential must agree to use an
effective nonhormonal method of contraception during therapy.
- ECOG performance status (PS) of 0 or 1 and/or Karnofsky PS of ≥70%.
- Diagnosis of invasive adenocarcinoma of the breast made by core needle biopsy.
- Palpable primary breast tumor measuring ≥ 2.0 cm on physical exam or imaging
- Patients with stage II-IIIA breast cancer that is HER2-negative by IHC (0-2+) and
- (HER2/CEP17 amplification ratio <2.0) for whom definitive surgical treatment after
- generation" neoadjuvant chemoT (see section 4.3.1) is planned. ER or PR receptors
status can be positive or negative. The receptor status needs to be recorded.
- Patients may have lymph node positive or negative disease, as long as they have
- II or IIIA breast cancer. Patients may have the lymph nodes assessed by any method
deemed appropriate by the treating physicians, including pre-neoadjuvant therapy
sentinel lymph node biopsy.
- Patients must discontinue sex hormone therapy prior to registration, e.g. birth
control pills, hormonal replacement therapy.
- At the time of registration:
- Absolute neutrophil count (ANC) must be ≥ 1200/mm3.
- Platelet count must be ≥ 100,000/mm3.
- Hemoglobin must be ≥ 9.0 mg/dL.
There must be evidence of adequate hepatic function by these criteria:
- Total bilirubin must be ≤ the ULN for the lab unless the patient has a grade 1
bilirubin elevation (> ULN to 1.5 x ULN) resulting from Gilbert's disease or similar
syndrome due to slow conjugation of bilirubin; and
- Alkaline phosphatase must be ≤ 2.5 x ULN for the lab
- AST/ALT must be ≤ 1.5 x ULN for the lab.
- Alkaline phosphatase and AST/ALT may not both be > the ULN. For example, if the
alkaline phosphatase is > the ULN but ≤ 2.5 x ULN, then the AST/ALT must be ≤ the
ULN. If the AST/ALT is > the ULN but ≤ 1.5 x ULN, then the alkaline phosphatase must
be ≤ ULN.
- Patients with either skeletal pain or alkaline phosphatase that is > ULN must
have a bone scan showing they do not have metastatic disease. Suspicious
findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
- Patients with AST/ALT or alkaline phosphatase > ULN must have liver imaging that
does not demonstrate metastatic disease.
- Patients with AST/ALT >ULN must have negative hepatitis studies.
- Patients with stage II disease and clinical suspicion for metastatic disease
based on reported symptoms, physical examination findings, or laboratory
abnormalities must have staging studies demonstrating no evidence of metastatic
disease (with exception of axillary lymph nodes or mammary nodes). Patients with
stage IIIA disease must have staging studies demonstrating no evidence of
metastatic disease (with exception of axillary lymph nodes or mammary nodes),
even if asymptomatic with normal physical examination and laboratory values.
Such staging studies must include: chest imaging (chest X-ray, CT, or MRI),
abdominal/pelvis imaging (CT or MRI), and bone imaging (bone scan or PET-scan).
Abnormalities that are indeterminate and too small to biopsy should be followed
with further imaging, as appropriate, but do not exclude patients from the
study. Abnormalities that are suspicious and large enough to biopsy exclude
patients from the study, unless a biopsy is performed and is negative for
- Serum creatinine ≤ 1.5 x ULN for the lab.
- Left Ventricular Ejection Fraction (LVEF) ≥ 50 % (by MUGA or echocardiography)
Patients with any of the following conditions will be ineligible for this study:
- Tumor determined to be HER2-positive by immunohistochemistry (3+) or by fluorescent
in situ hybridization (HER2/CEP17 amplification ratio ≥2.0).
- Tumors clinically staged as T4 or N3.
- Definitive evidence of metastatic disease with exception of axillary lymph nodes or
- Synchronous bilateral breast cancer (invasive or DCIS).
- Treatment including radiation therapy, chemoT, biotherapy, and/or hormonal therapy
for the currently diagnosed breast cancer prior to study entry
- Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement
therapy, etc. (These patients are eligible if this therapy is discontinued 1 week
prior to registration)
- Prior history of invasive breast cancer (Patients with a history of DCIS or LCIS are
- Prior therapy with anthracyclines for any malignancy.
- Other malignancies unless the patient is considered to be disease-free for 5 or more
years prior to randomization and is deemed by the physician to be at low risk for
- Patients with the following cancers are eligible if diagnosed and treated within the
- years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in
situ, and basal cell or squamous cell carcinoma of the skin.
- Known cardiac disease that would preclude the use of anthracyclines. This includes:
- angina pectoris that requires the use of anti-anginal medication
- history of documented congestive heart failure
- serious cardiac arrhythmia requiring medication
- severe conduction abnormality
- valvular disease with documented cardiac function compromise; and
- uncontrolled hypertension defined as BP that is consistently > 150/90 on
antihypertensive therapy at the time of registration. (Patients with hypertension
that is well controlled on medication are eligible.)
- History of myocardial infarction (MI) documented by elevated cardiac enzymes with
persistent regional wall motion abnormality on assessment of LV function. (Patients
with history of MI must have an echo instead of/in addition to a MUGA to evaluate LV
- Symptomatic peripheral vascular disease.
- Sensory/motor neuropathy ≥ grade 2, as defined by the NCI's Common Terminology
Criteria for Adverse Events Version 4.0 (CTCAE v4.0).
- Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that
- preclude treatment with any of the treatment regimens or would prevent required
- Chronic ongoing steroid use at the time of registration for any condition (such as
- rheumatoid arthritis, etc).
- Administration of any investigational agents within 30 days before study entry.
- Pregnancy or lactation at the time of registration.
- Psychiatric or addictive disorders or other conditions that in the opinion of the
investigators would preclude the patient from complying with the study protocol.