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• Status: Withdrawn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.