Overview

Trial of Neoadjuvant Trastuzumab Emtansine in Patients With HER2-Equivocal Breast Cancer

Status:
Withdrawn
Trial end date:
2019-05-01
Target enrollment:
0
Participant gender:
Female
Summary
This is an open label, neoadjuvant phase II study to evaluate the objective response, toxicity, and safety of trastuzumab emtansine in patients with newly diagnosed HER2-equivocal breast cancer. Trastuzumab emtansine at a dose of 3.6 mg/kg will be intravenously administered every 3 weeks for a total of 6 weeks. Patients who achieve a partial or complete response after the 6-week treatment (responders) will continue on trastuzumab emtansine for an additional 12 weeks.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Jenny C. Chang, MD
Collaborators:
Genentech, Inc.
The Methodist Hospital Research Institute
The Methodist Hospital System
Treatments:
Ado-Trastuzumab Emtansine
Maytansine
Trastuzumab
Criteria
Inclusion Criteria:

- Female gender;

- Age ≥18 years;

- Eastern Cooperative Oncology Group performance status of 0-1;

- Histologically confirmed invasive breast cancer;

- Primary tumor greater than or equal to 1 cm diameter, as measured by clinical
examination and mammography or ultrasound;

- Any N;

- No evidence of metastasis (M0) (isolated supra-clavicular node involvement allowed);

- HER2 low or equivocal status in the invasive component of the primary tumor (confirmed
by a central certified laboratory prior to study entry)

- HER2 low expression: 1+/2+ by immunohistochemistry and/or HER2/CEP17 ratio <2.0
with HER2 copy number <6.0 signals/cell

- HER2 equivocal expression: HER2 copy number ≥4.0 and <6.0 signals/cell;

- Hematopoietic status:

Absolute neutrophil count ≥ 1.0 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Hemoglobin at
least 9 g/dL;

• Hepatic status: Serum total bilirubin ≤1 x upper limit of normal (ULN; In the case of
known Gilbert's syndrome, a higher serum total bilirubin [< 1.5 x ULN] is allowed),
Aspartate aminotransferase and alanine aminotransferase ≤1.5 x ULN, Alkaline phosphatase ≤
1.5 x ULN;

• Renal status: Creatinine ≤1.5 mg/dL;

- International Normalized Ratio ≤1.5 x ULN;

- Baseline left ventricular ejection fraction ≥50%, as measured by echocardiography or
multigated acquisition scan;

- Negative serum or urine β-human chorionic gonadotropin pregnancy test within 7 days
prior study entry for patients of childbearing potential. Women of childbearing
potential must use effective contraception (barrier method [condoms, diaphragm] in
conjunction with spermicidal jelly, or total abstinence. Oral, injectable, and
implantable hormonal contraceptives are not allowed) for the duration of the study and
for at least 7 months after the last dose of study treatment;

- Signed informed consent form (ICF);

- Patient accepts to make available tumor samples for submission to central laboratory
to conduct translational studies as part of this protocol.

Exclusion Criteria:

- Previous (less than 5 years) or current history of malignant neoplasms, except for
curatively treated basal and squamous cell carcinoma of the skin and carcinoma in situ
of the cervix;

- Patients with a prior malignancy diagnosed more than 5 years prior to study entry;

- Preexisting peripheral neuropathy ≥ grade 2;

- Known history of uncontrolled or symptomatic angina, clinically significant
arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled
hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic
oxygen therapy;

- Concurrent disease or condition that would make the patient inappropriate for study
participation or any serious medical disorder that would interfere with the patient's
safety;

- Unresolved or unstable serious adverse events from prior administration of another
investigational drug;

- Dementia, altered mental status, or any psychiatric condition that would prevent the
understanding or rendering of ICF;

- Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy,
or biologic therapy other than the trial therapy);

- Concurrent treatment with an investigational agent or participation in another
therapeutic clinical trial;

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to trastuzumab emtansine or its components;

- Ejection fraction <55% or below the lower limit of the institutional normal range;

- Pregnant or lactating women;

- Concomitant use of cytochrome P450 3A4 inhibitors or inducers;

- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable
safety risks or compromise compliance with the protocol;

- Active infection requiring intravenous or oral antibiotics;

- Patients unwilling or unable to comply with the protocol.