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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)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01772472
First Posted: January 21, 2013
Last Update Posted: October 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
NSABP Foundation Inc
German Breast Group
Information provided by (Responsible Party):
Hoffmann-La Roche
  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.

Condition Intervention Phase
Breast Cancer Drug: trastuzumab Drug: trastuzumab emtansine Phase 3

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Invasive disease-free survival including second non-breast cancers [ Time Frame: up to 10 years ]
  • 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 ]
  • Overall survival: Time from randomization to death of any cause [ Time Frame: up to 10 years ]
  • Distant recurrence-free interval: Time from randomization to date of distant breast cancer recurrence [ Time Frame: up to 10 years ]
  • Safety: Incidence of adverse events [ Time Frame: up to 10 years ]
  • Incidence of cardiac events: Death from cardiac cause or severe chronic heart failure (NYHA Class III or IV) [ Time Frame: up to 10 years ]
  • 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 ]

Enrollment: 1487
Actual Study Start Date: April 5, 2013
Estimated Study Completion Date: March 31, 2023
Estimated Primary Completion Date: March 31, 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Trastuzumab Drug: trastuzumab
6 mg/kg intravenously every 3 weeks, 14 cycles
Experimental: Trastuzumab emtansine Drug: trastuzumab emtansine
3.6 mg/kg intravenously every 3 weeks, 14 cycles

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01772472


  Show 328 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
NSABP Foundation Inc
German Breast Group
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01772472     History of Changes
Other Study ID Numbers: BO27938
2012-002018-37
First Submitted: January 17, 2013
First Posted: January 21, 2013
Last Update Posted: October 16, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm, Residual
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Ado-trastuzumab emtansine
Trastuzumab
Maytansine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action