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 currently recruiting participants.
Verified July 2013 by Hoffmann-La Roche
Sponsor:
Hoffmann-La Roche
Collaborators:
National Surgical Adjuvant Breast and Bowel Project (NSABP)
German Breast Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01772472
First received: January 17, 2013
Last updated: July 29, 2013
Last verified: July 2013
History of Changes
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.
Study Type: Interventional Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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:
Genetics Home Reference related topics:
breast cancer
MedlinePlus related topics:
Breast Cancer Cancer
Drug Information available for:
Trastuzumab Trastuzumab emtansine
U.S. FDA Resources
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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Invasive disease-free survival including second non-breast cancers [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Overall survival: Time from randomization to death of any cause [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
- Distant recurrence-free interval: Time from randomization to date of distant breast cancer recurrence [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
- Safety: Incidence of adverse events [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
- Incidence of cardiac events: Death from cardiac cause or severe chronic heart failure (NYHA Class III or IV) [ Time Frame: up to 10 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
Estimated Enrollment: 1484 Study Start Date: April 2013 Estimated Study Completion Date: March 2023 Estimated Primary Completion Date: March 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions Experimental: Trastuzumab emtansine Drug: trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks, 14 cycles
Active Comparator: Trastuzumab Drug: trastuzumab 6 mg/kg intravenously every 3 weeks, 14 cycles
Eligibility
Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both 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 treatment consisting of at least 6 cycles 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
- Left ventricular ejection fraction (LVEF) >/= 50% at screening and no decrease in LVEF by more than 15% absolute points from pre-chemotherapy
- Women of childbearing potential and men with partners of childbearing potential must be willing to use effective contraception as defined by protocol for the duration of study treatment and for at least 6 months after the last dose of study treatment
- 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 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 > 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 or known infection with HIV
- History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01772472
Contacts
Contact: Reference Study ID Number: BO27938
www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com
Show 276 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
National Surgical Adjuvant Breast and Bowel Project (NSABP)
German Breast Group
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
More Information
No publications provided
Responsible Party: Hoffmann-La Roche ClinicalTrials.gov Identifier:
NCT01772472 History of Changes Other Study ID Numbers: BO27938, 2012-002018-37 Study First Received: January 17, 2013 Last Updated: July 29, 2013 Health Authority: United States: Food and Drug Administration
Additional relevant MeSH terms: Breast Neoplasms
Neoplasm, Residual
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Trastuzumab
Maytansine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
ClinicalTrials.gov processed this record on August 01, 2013
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