Description:
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.
Title
- Brief Title: 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)
- 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
Clinical Trial IDs
- ORG STUDY ID:
BO27938
- SECONDARY ID:
2012-002018-37
- NCT ID:
NCT01772472
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| trastuzumab | | Trastuzumab |
| trastuzumab emtansine | | Trastuzumab emtansine |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Trastuzumab | Active Comparator | | |
| Trastuzumab emtansine | Experimental | | |
Eligibility Criteria
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
eligible)
- 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
therapy
- 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
randomization
- 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
situ
- 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
HIV
- History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity
to trastuzumab or murine proteins or any components of the product
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Invasive disease-free survival (IDFS): Time from randomization to ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death of any cause |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Invasive disease-free survival including second non-breast cancers |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
| Measure: | Disease-free survival: Time from randomization to first occurrence of an IDFS event including second primary non-breast cancer or contralateral or ipsilateral ductal carcinoma in situ |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
| Measure: | Overall survival: Time from randomization to death of any cause |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
| Measure: | Distant recurrence-free interval: Time from randomization to date of distant breast cancer recurrence |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
| Measure: | Safety: Incidence of adverse events |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
| Measure: | Incidence of cardiac events: Death from cardiac cause or severe chronic heart failure (NYHA Class III or IV) |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
| Measure: | Patient reported outcomes: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Quetionnaire QLQ-C30/QLQ-BR23, EuroQol EQ-5d Questionnaire |
| Time Frame: | up to 10 years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
January 22, 2018
