A Randomized Phase II Trial of Adjuvant Trastuzumab Emtansine (T-DM1) Followed by Subcutaneous Trastuzumab Versus Paclitaxel in Combination With Subcutaneous Trastuzumab for Stage I HER2-positive Breast Cancer (ATEMPT 2.0)
Summary
This research study is studying how well newly diagnosed breast cancer that has tested positive for a protein called HER2 responds using one of two different combination of HER2-directed therapies as a treatment after surgery. The name of the study drugs involved are: * Trastuzumab-emtansine (T-DM1, Kadcyla) * Trastuzumab SC (Herceptin Hylecta) * Paclitaxel
Detailed description
This is a randomized phase II adjuvant study for women and men with Stage I HER2-positive invasive breast cancer. Participants will be randomized into one of two treatment arms in this study and receive: * Arm 1: trastuzumab-emtansine (T-DM1, Kadcyla) and trastuzumab SC (Herceptin Hylecta) * Arm 2: paclitaxel and trastuzumab SC (Herceptin Hylecta) This research study is looking to see if the study drug T-DM1 followed by trastuzumab SC will have less side-effects than traditional HER2-positive breast cancer treatment of trastuzumab and paclitaxel.The study is also looking to learn about the long-term benefits and disease-free survival of participants who are treated with T-DM1 followed by trastuzumab SC. T-DM1 is an antibody-drug conjugate; it is made up of an antibody (trastuzumab) linked to a cytotoxic drug, DM1 (chemotherapy). T-DM1 functions as a targeted cancer therapy because it targets HER2-positive breast cancer cells directly, limiting exposure of the rest of the body to chemotherapy. More specifically, the trastuzumab in T-DM1 first binds to the HER2 protein on the surface of the breast cancer cells and the DM1 then enters the cells and can cause them to die, preventing tumor growth. The FDA (the U.S. Food and Drug Administration) has not approved T-DM1 for use on its own in patients with stage I, II, or III breast cancer. However, it has been approved for use in (a) advanced or metastatic, previously treated breast cancer and (b) in some patients receiving postoperative treatment after preoperative chemotherapy and surgery have been completed. Trastuzumab SC is a subcutaneous form of trastuzumab.Trastuzumab is a monoclonal antibody, which are disease-fighting proteins made by cloned immune cells. Paclitaxel and trastuzumab are considered a standard-of-care regimen in early breast cancer. Trastuzumab is FDA-approved to be administered as an IV (intravenous) or subcutaneous (muscular injection). The research study procedures include screening for eligibility and study treatment including laboratory evaluations and follow up visits. Participants will receive study treatment for a year in total and will be followed for 5 years after treatment. It is expected that about 500 people will take part in this research study. Genentech is supporting this research study by providing funding for the study and supplying trastuzumab-emtansine (T-DM1) and trastuzumab SC (subcutaneous).
Arms & interventions
- Drugtrastuzumab-emtansine
intravenous infusion
- DrugTrastuzumab SC
Muscular injection
- DrugPaclitaxel
intravenous infusion
Outcome measures
Primary
Incidence of clinically relevant toxicities (CRT)
Compare the incidence of clinically relevant toxicities (CRT) in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine followed by trastuzumab SC to the incidence in those treated with paclitaxel in combination with trastuzumab SC as assessed by PRO-CTCAE
Time frame: First 18 weeks of treatment
Disease Free Survival (DFS)
Evaluate disease-free survival in the T-DM1 followed by trastuzumab SC arm
Time frame: Time from randomization to first Disease Free Survival (DFS) event up to 72 months
Secondary
Grade 3 and 4 adverse events
Time frame: Enrollment to end of treatment up to 1 year
Quality of Life Assessment: FACT B
Time frame: Enrollment to end of treatment up to 1 year
Symptoms related to therapy
Time frame: Enrollment to end of treatment up to 1 year
Symptoms related to therapy
Time frame: Enrollment to end of treatment up to 1 year
Effects of therapy on work productivity
Time frame: Enrollment to end of treatment up to 1 year
Effect of alopecia on patients
Time frame: Enrollment to end of treatment up to 1 year
Incidence of Side Effects
Time frame: Enrollment to end of treatment up to 1 year
Incidence of grade 3-4 cardiac left ventricular dysfunction
Time frame: Enrollment to end of treatment up to 1 year
Incidence of trastuzumab-emtansine-induced grade 2-4 thrombocytopenia
Time frame: Enrollment to end of treatment up to 1 year
Percentage of patients with amenorrhea
Time frame: Enrollment to end of treatment up to 1 year
Evaluation of gene predictors of trastuzumab-emtansine-induced grade 2-4
Time frame: Enrollment to end of treatment up to 1 year
Gene Profiling
Time frame: Enrollment to end of treatment up to 1 year
Radiation therapy Toxicity
Time frame: Enrollment to end of treatment up to 1 year
Overall survival
Time frame: Enrollment to end of treatment up to 1 year
Eligibility criteria
Study locations (53)
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Smilow Cancer Hospital Care center at Derby
Derby, Connecticut, 06418
Smilow Cancer Hospital Care center at Fairfield
Fairfield, Connecticut, 06824
Smilow Cancer Hospital Care center at Glastonbury
Glastonbury, Connecticut, 06033
Smilow Cancer Hospital Care center at Greenwich
Greenwich, Connecticut, 06830
Smilow Cancer Hospital Care center at Guilford
Guilford, Connecticut, 06437
Smilow Cancer Hospital Care center at St. Francis
Hartford, Connecticut, 06105
Smilow Cancer Hospital Care center at Long Ridge
Long Ridge, Connecticut, 06902
Yale Cancer Center at Yale University School of Medicine
New Haven, Connecticut, 06520-8028
Smilow Cancer Hospital Care center at North Haven
North Haven, Connecticut, 06510
Stamford Hospital
Stamford, Connecticut, 06904
Smilow Cancer Hospital Care center at Torrington
Torrington, Connecticut, 06790
Smilow Cancer Hospital Care center at Trumbull
Trumbull, Connecticut, 06611
Smilow Cancer Hospital Care center at Waterbury
Waterbury, Connecticut, 06708
Smilow Cancer Hospital Care center at Waterford
Waterford, Connecticut, 06385
Miami Cancer Institute/Baptist Hospital of Miami
Miami, Florida, 33176
Miami Cancer Institute - Plantation (MCIP)
Plantation, Florida, 33324
The University of Chicago Medical Center
Chicago, Illinois, 60637
Indiana University Health Joe & Shelly Schwarz Cancer Center
Carmel, Indiana, 46032
IU Health North Hospital
Carmel, Indiana, 46032
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
Indiana University Sidney and Lois Eskenazi Hospital
Indianapolis, Indiana, 46202
Eastern Maine Medical Center (Northern Light)
Brewer, Maine, 04412
New England Cancer Specialists
Scarborough, Maine, 04074
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Massachusetts General Hospital
Boston, Massachusetts, 02215
Dana-Farber at St. Elizabeth's Medical Center
Brighton, Massachusetts, 02135
Lahey Clinic
Burlington, Massachusetts, 01805
Mass General North Shore Cancer Center
Danvers, Massachusetts, 01923
Dana-Farber Brigham Cancer Center - Foxborough
Foxborough, Massachusetts, 02035
Dana-Farber Cancer Instiute - Merrimack Valley
Methuen, Massachusetts, 01844
Dana-Farber at Milford
Milford, Massachusetts, 01757
Newton Wellesley Hospital
Newton, Massachusetts, 02462
Berkshire Medical Center
Pittsfield, Massachusetts, 01201
Dana Farber at South Shore Hospital
Weymouth, Massachusetts, 02190
NH Oncology-Hematology, PA - Payson Center for Cancer Care
Concord, New Hampshire, 03301
Dana-Farber Cancer Insitute at Londonderry Hospital
Londonderry, New Hampshire, 03053
Solinsky Center for Cancer Care (NH Oncology-Hematology, PA)
Manchester, New Hampshire, 03103
New England Cancer Specialists - Portsmouth
Portsmouth, New Hampshire, 03801
New York University Langone Hospital -Brooklyn
Brooklyn, New York, 11220
New York University Langone Hospital - Long Island
Mineola, New York, 11501
New York University Langone Health
New York, New York, 10016
Northwell University
New York, New York, 10075
Duke University Medical Center
Durham, North Carolina, 27710
Duke Women's Cancer Care Raleigh
Raleigh, North Carolina, 27710
Stefanie Spielman Comprehensive Breast Center
Columbus, Ohio, 43212
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center Cancer UPMC- Magee Women's Hospital
Pittsburgh, Pennsylvania, 15213
Smilow Cancer Hospital Care center at Westerly
Westerly, Rhode Island, 02891
Greco-Hainsworth Centers for Research/Tennessee Oncology
Nashville, Tennessee, 37203
SCRI Oncology Partners
Nashville, Tennessee, 37203
MD Anderson Cancer Center
Houston, Texas, 77030