A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)

Not Recruiting

Trial ID: NCT01772472


This 2-arm, randomized, open-label study will evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. Radiotherapy and/or hormone therapy will be given in addition if indicated.

Official Title

A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy for Patients With HER2-Positive Primary Breast Cancer Who Have Residual Tumor Present Pathologically in the Breast or Axillary Lymph Nodes Following Preoperative Therapy

Stanford Investigator(s)

Irene Wapnir, MD
Irene Wapnir, MD

Professor of Surgery (General Surgery)


Inclusion Criteria:

   - Adult patient, >/= 18 years of age

   - HER2-positive breast cancer

   - Histologically confirmed invasive breast carcinoma

   - Clinical stage T1-4/N0-3/M0 at presentation (patients with T1a/bN0 tumors will not be

   - Completion of preoperative systemic chemotherapy and HER2-directed treatment
   consisting of at least 6 cycles of chemotherapy with a total duration of at least 16
   weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based

   - Adequate excision: surgical removal of all clinically evident disease in the breast
   and lymph nodes as specified in protocol

   - Pathological evidence of residual invasive carcinoma in the breast or axillary lymph
   nodes following completion of preoperative therapy

   - An interval of no more than 12 weeks between the date of surgery and the date of

   - Known hormone-receptor status

   - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

   - Adequate hematologic, renal and liver function

   - Screening Left ventricular ejection fraction (LVEF) >/= 50% on echocardiogram (ECHO)
   or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no
   decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or,
   if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >/= 55% after
   completion of neoadjuvant chemotherapy.

   - For women who are not postmenopausal or surgically sterile: agreement to remain
   abstinent or use single or combined contraceptive methods that result in a failure
   rate of < 1% per year during the treatment period and for at least 7 months after the
   last dose of study drug

   - Documentation of hepatitis B virus and hepatitis C virus serology is required

Exclusion Criteria:

   - Stage IV (metastatic) breast cancer

   - History of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in

   - Evidence of clinically evident gross residual or recurrent disease following
   preoperative therapy and surgery

   - Progressive disease during preoperative systemic therapy

   - Treatment with any anti-cancer investigational drug within 28 days prior to commencing
   study treatment

   - History of other malignancy within the last 5 years except for appropriately treated
   carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
   or other non-breast malignancies with a similar outcome to those mentioned above

   - Patients for whom radiotherapy would be recommended for breast cancer treatment but
   for whom it is contraindicated because of medical reasons

   - Current NCI CTCAE (Version 4.0) Grade >/= 2 peripheral neuropathy

   - History of exposure to the following cumulative doses of anthracyclines: Doxorubicin >
   240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) > 480 mg/m2;
   For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2

   - Cardiopulmonary dysfunction as defined by protocol

   - Prior treatment with trastuzumab emtansine

   - Current severe, uncontrolled systemic disease

   - Pregnant or lactating women

   - Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or
   sclerosing cholangitis

   - Concurrent serious uncontrolled infections requiring treatment or known infection with

   - History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity
   to trastuzumab or murine proteins or any components of the product


drug: trastuzumab emtansine

drug: trastuzumab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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