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:
Collaborators:
German Breast Group
NSABP Foundation Inc
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01772472
First received: January 17, 2013
Last updated: July 1, 2016
Last verified: July 2016
  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: 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:


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 ]

Enrollment: 1487
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
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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772472

  Hide Study Locations
Locations
United States, Alaska
Anchorage, Alaska, United States, 99508
United States, California
Long Beach, California, United States, 90806
Orange, California, United States, 92868
San Diego, California, United States, 92120
Santa Ana, California, United States, 92705
Stanford, California, United States, 94305-5236
Vallejo, California, United States, 94589
United States, Colorado
Denver, Colorado, United States, 80205
Denver, Colorado, United States, 80222
Lone Tree, Colorado, United States, 80124
Wheat Ridge, Colorado, United States, 80033
United States, Connecticut
Hartford, Connecticut, United States, 06102
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Washington, District of Columbia, United States, 20010
United States, Florida
Gainesville, Florida, United States, 32610
Jacksonville, Florida, United States, 32207
Miami Beach, Florida, United States, 33140
Orlando, Florida, United States, 32806
Tampa, Florida, United States, 33612-9497
United States, Georgia
Albany, Georgia, United States, 31701
United States, Illinois
Chicago, Illinois, United States, 60612
Naperville, Illinois, United States, 60540
Plainfield, Illinois, United States, 60585
United States, Iowa
Iowa City, Iowa, United States, 52242
United States, Kentucky
Lexington, Kentucky, United States, 40536
Louisville, Kentucky, United States, 40202
United States, Maine
Augusta, Maine, United States, 04330
Brewer, Maine, United States, 04412
Scarborough, Maine, United States, 04074
United States, Maryland
Baltimore, Maryland, United States, 21202
Baltimore, Maryland, United States, 21237
Baltimore, Maryland, United States, 21218
Baltimore, Maryland, United States, 21204
United States, Michigan
Detroit, Michigan, United States, 48201
Detroit, Michigan, United States, 48202
Grand Rapids, Michigan, United States, 49503
Lansing, Michigan, United States, 48910
Owosso, Michigan, United States, 48867
Royal Oak, Michigan, United States, 48073
Traverse City, Michigan, United States, 49614
United States, Minnesota
Saint Louis Park, Minnesota, United States, 55416
United States, Missouri
Joplin, Missouri, United States, 64804
Springfield, Missouri, United States, 65804
United States, Nevada
Las Vegas, Nevada, United States, 89106
United States, New Jersey
Long Branch, New Jersey, United States, 07740
New Brunswick, New Jersey, United States, 08901
Newark, New Jersey, United States, 07112
Sparta, New Jersey, United States, 07871-1791
United States, New York
Glenn Falls, New York, United States, 12801
New York, New York, United States, 10032
Stony Brook, New York, United States, 11794
Troy, New York, United States, 12180
United States, North Carolina
Charlotte, North Carolina, United States, 28204-2839
Concord, North Carolina, United States, 28025
Monroe, North Carolina, United States, 28211
Shelby, North Carolina, United States, 28150
United States, North Dakota
Fargo, North Dakota, United States, 58122-9988
United States, Ohio
Akron, Ohio, United States, 44304
Canton, Ohio, United States, 44710
Cleveland, Ohio, United States, 44106-5067
Cleveland, Ohio, United States, 44111
Cleveland, Ohio, United States, 44195
Columbus, Ohio, United States, 43210
Mayfield Heights, Ohio, United States, 44124
Mentor, Ohio, United States, 44060
United States, Oregon
Portland, Oregon, United States, 97225
United States, Pennsylvania
East Stroudsburg, Pennsylvania, United States, 18301
Ephrata, Pennsylvania, United States, 17543
Philadelphia, Pennsylvania, United States, 19107
Pittsburgh, Pennsylvania, United States, 15212
Pittsburgh, Pennsylvania, United States, 15213
York, Pennsylvania, United States, 17403
United States, South Carolina
Charleston, South Carolina, United States, 29425
United States, South Dakota
Sioux Falls, South Dakota, United States, 57105
Sioux Falls, South Dakota, United States, 57104
United States, Tennessee
Knoxville, Tennessee, United States, 37916-2305
United States, Texas
Houston, Texas, United States, 77030
Lubbock, Texas, United States, 79410
United States, Virginia
Fredericksburg, Virginia, United States, 22408
Lynchburg, Virginia, United States, 24501
Richmond, Virginia, United States, 23298
United States, Washington
Issaquah, Washington, United States, 98029
Kirkland, Washington, United States, 98034
Longview, Washington, United States, 98632
Mount Vernon, Washington, United States, 98274
Seattle, Washington, United States, 98101
Spokane, Washington, United States, 99204
United States, Wisconsin
Marshfield, Wisconsin, United States, 54449
Milwaukee, Wisconsin, United States, 53215
Argentina
Caba, Argentina, C1025ABI
Ciudad Autonoma Buenos Aires, Argentina, C1284AEB
La Rioja, Argentina, F5300COE
Rosario, Argentina, S2000KZE
Austria
Innsbruck, Austria, 6020
Salzburg, Austria, 5020
Wien, Austria, 1090
Belgium
Bruxelles, Belgium, 1200
Gent, Belgium, 9000
Liège, Belgium, 4000
Wilrijk, Belgium, 2610
Brazil
Curitiba, PR, Brazil, 80530-010
Rio De Janeiro, RJ, Brazil, 22290-160
Rio de Janeiro, RJ, Brazil, 20230-130
Porto Alegre, RS, Brazil, 91350-200
Porto Alegre, RS, Brazil, 90540-140
Porto Alegre, RS, Brazil, 90035-001
Barretos, SP, Brazil, 14784-400
Jau, SP, Brazil, 17210-080
Sao Jose dos Campos, SP, Brazil, 12245-750
Sao Paulo, SP, Brazil, 01321-000
Sao Paulo, SP, Brazil, 01246-000
Sao Paulo, SP, Brazil, 01317-000
Sao Paulo, SP, Brazil, 01236-030
São Paulo, SP, Brazil, CEP 01321-001
Canada, Alberta
Calgary, Alberta, Canada, T2N 4N2
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Surrey, British Columbia, Canada, V3V 1Z2
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
London, Ontario, Canada, N6A 4L6
Ottawa, Ontario, Canada, K1H 8L6
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Greenfield Park, Quebec, Canada, J4V 2H1
Montreal, Quebec, Canada, H3T 1E2
Montreal, Quebec, Canada, H2X 0A9
Montreal, Quebec, Canada, H3G 1A4
Canada
Quebec, Canada, G1S 4L8
China
Changchun, China, 130021
Guangzhou, China, 510060
Guangzhou, China
Harbin, China, 150081
Jinan, China, 250117
Nanjing, China, 210036
Shanghai, China, 200025
Shanghai, China, 200032
Shijiazhuang, China, 050035
Colombia
Bogota, Colombia, 11001
Bogota, Colombia
Medellin-Antioquia, Colombia
Monteria, Colombia
Czech Republic
Hradec Kralove, Czech Republic, 500 05
Olomouc, Czech Republic, 775 20
Praha 2, Czech Republic, 128 08
France
Avignon, France, 84918
Besancon, France, 25030
Bordeaux, France, 33076
Bordeaux, France, 33077
Bourg En Bresse, France, 01012
Caen, France, 14076
Clermont Ferrand, France, 63011
Le Mans, France, 72015
Marseille, France, 13273
Montpellier, France, 34298
Paris, France, 75231
Paris, France, 75475
Paris, France, 75970
Rouen, France, 76038
St Cloud, France, 92210
Strasbourg, France, 67065
Villejuif, France, 94805
Germany
Augsburg, Germany, 86150
Berlin, Germany, 10367
Berlin, Germany, 10707
Berlin, Germany, 13125
Berlin, Germany, 14169
Bielefeld, Germany, 33604
Böblingen, Germany, 71032
Chemnitz, Germany, 09116
Dortmund, Germany, 44137
Düsseldorf, Germany, 40235
Erlangen, Germany, 91054
Essen, Germany, 45122
Essen, Germany, 45136
Esslingen, Germany, 73730
Frankfurt, Germany, 60596
Frankfurt, Germany, 60431
Frankfurt am Main, Germany, 60389
Freiburg, Germany, 79106
Fürth, Germany, 90766
Gelsenkirchen, Germany, 45879
Greifswald, Germany, 17475
Halle, Germany, 06110
Halle, Germany, 06120
Hamburg, Germany, 20357
Hamm, Germany, 59073
Hannover, Germany, 30177
Hannover, Germany, 30559
Hannover, Germany, 30625
Heidelberg, Germany, 69120
Karlsruhe, Germany, 76135
Kassel, Germany, 34117
Kassel, Germany, 34125
Kiel, Germany, 24105
Koeln, Germany, 50935
Köln, Germany, 51067
Lebach, Germany, 66822
Limburg, Germany, 65549
Lörrach, Germany, 79539
Minden, Germany, 32429
München, Germany, 80337
München, Germany, 80638
Münster, Germany, 48149
Nordhausen, Germany, 99734
Offenbach, Germany, 63069
Paderborn, Germany, 33098
Recklinghausen, Germany, 45657
Reutlingen, Germany, 72764
Rostock, Germany, 18059
Stralsund, Germany, 18435
Stuttgart, Germany, 70376
Traunstein, Germany, 83278
Tübingen, Germany, 72076
Ulm, Germany, 89075
Wiesbaden, Germany, 65199
Witten, Germany, 58452
Würzburg, Germany, 97080
Greece
Heraklion, Greece, 711 10
Thessaloniki, Greece, 546 45
Guatemala
Guatemala, Guatemala, 01010
Guatemala City, Guatemala, 01015
Hong Kong
Hong Kong, Hong Kong
Hong Kong, Hong Kong, 852
Ireland
Cork, Ireland
Dublin, Ireland, 9
Dublin, Ireland, 4
Dublin, Ireland, 7
Galway, Ireland
Limerick, Ireland
Israel
Beer Sheva, Israel, 8410101
Jerusalem, Israel, 9112001
Jerusalem, Israel, 9372212
Petach Tikva, Israel, 4941492
Ramat Gan, Israel, 5262100
Rehovot, Israel, 7610001
Italy
Napoli, Campania, Italy, 80131
Bologna, Emilia-Romagna, Italy, 40138
Bologna, Emilia-Romagna, Italy, 40139
Roma, Lazio, Italy, 00128
Roma, Lazio, Italy, 00189
Genova, Liguria, Italy, 16132
Bergamo, Lombardia, Italy, 24128
Cremona, Lombardia, Italy, 26100
Milano, Lombardia, Italy, 20132
Milano, Lombardia, Italy, 20133
Milano, Lombardia, Italy, 20141
Monza, Lombardia, Italy, 20900
Rozzano, Lombardia, Italy, 20089
Macerata, Marche, Italy, 62100
Candiolo, Piemonte, Italy, 10060
Brindisi, Puglia, Italy, 72100
San Giovanni Rotondo, Puglia, Italy, 71013
Pisa, Toscana, Italy, 56100
Pontedera, Toscana, Italy, 56025
Padova, Veneto, Italy, 35128
Verona, Veneto, Italy, 37126
Mexico
Aguascalientes, Mexico, 20230
Distrito Federal, Mexico, 14080
Mexico City, Mexico, 06760
Mexico City, Mexico, 14080
Oaxaca, Mexico, 68000
Panama
Panama, Panama, 0834-02723
Panama City, Panama, 0832-00752
Peru
Arequipa, Peru, 04001
Bellavista, Peru, Callao 2
Lima, Peru, 13
Lima, Peru, Lima 41
Miraflores, Peru, Lima 18
Serbia
Belgrade, Serbia, 11000
Kragujevac, Serbia, 34000
Sremska Kamenica, Serbia, 21204
South Africa
Johannesburg, South Africa, 2193
Johannesburg, South Africa, 2196
Kraaifontein, South Africa, 7570
Pietermaritzburg, South Africa, 3201
Port Elizabeth, South Africa, 6045
Pretoria, South Africa, 0081
Spain
Terrassa, Barcelona, Spain, 08221
Cádiz, Cadiz, Spain, 11009
San Sebastian, Guipuzcoa, Spain, 20080
Alcorcon, Madrid, Spain, 28922
Leganes, Madrid, Spain, 28911
Vigo, Pontevedra, Spain, 36312
Reus, Tarragona, Spain, 43204
Barcelona, Spain, 08036
Madrid, Spain, 28046
Madrid, Spain, 28050
Malaga, Spain, 29010
Navarra, Spain, 31008
Salamanca, Spain, 37007
Sevilla, Spain, 41013
Valencia, Spain, 46017
Valencia, Spain, 46009
Valencia, Spain, 41014
Sweden
Gävle, Sweden, 80187
Lund, Sweden, 22185
Stockholm, Sweden, 17176
Switzerland
Aarau, Switzerland, 5001
Zürich, Switzerland, 8008
Taiwan
Taichung, Taiwan, 407
Taipei, Taiwan, 00112
Taipei, Taiwan, 100
Taipei, Taiwan, 112
Taoyuan, Taiwan, 333
Turkey
Bursa, Turkey, 16059
Edirne, Turkey, 22770
Istanbul, Turkey, 34000
Izmir, Turkey, 35100
Malatya, Turkey, 44280
United Kingdom
Birmingham, United Kingdom, B15 2TH
Bradford, United Kingdom, BD9 6RJ
Bristol, United Kingdom, BS2 8ED
Cottingham, United Kingdom, HU16 5JG
Devon, United Kingdom, EX31 4JB
Dundee, United Kingdom, DD1 9SY
Huddersfield, United Kingdom, HD3 3EA
Leeds, United Kingdom, LS9 7TF
London, United Kingdom, SE1 7EH
London, United Kingdom, W6 8RF
Manchester, United Kingdom, M2O 4BX
Nottingham, United Kingdom, NG5 1PB
Sheffield, United Kingdom, S10 2SJ
Truro, United Kingdom, TR1 3LJ
Sponsors and Collaborators
Hoffmann-La Roche
German Breast Group
NSABP Foundation Inc
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 
Study First Received: January 17, 2013
Last Updated: July 1, 2016
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
Ado-trastuzumab emtansine
Trastuzumab
Maytansine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2016