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
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
500
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
Grade 3 and 4 adverse events
Compare the incidence of all grade 3 and 4 adverse events in patients treated with adjuvant trastuzumab emtansine followed by trastuzumab SC to the incidence in those receiving paclitaxel in combination with trastuzumab SC
Time frame: Enrollment to end of treatment up to 1 year
Quality of Life Assessment: FACT B
Compare responses to FACT-B quality of life (QOL) questionnaire in patients receiving trastuzumab emtansine followed by trastuzumab SC to that experienced by patients receiving paclitaxel in combination with trastuzumab SC.
Time frame: Enrollment to end of treatment up to 1 year
Symptoms related to therapy
Evaluate symptoms related to therapy in patients receiving trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel in combination with trastuzumab SC using the Rotterdam Symptom Checklist (RSCL)
Time frame: Enrollment to end of treatment up to 1 year
Symptoms related to therapy
Evaluate symptoms related to therapy in patients receiving trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel in combination with trastuzumab SC using the Patient Neurotoxicity Questionnaire (PNQ)
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UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
RECRUITINGSmilow Cancer Hospital Care center at Derby
Derby, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care center at Fairfield
Fairfield, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care center at Glastonbury
Glastonbury, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care center at Greenwich
Greenwich, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care center at Guilford
Guilford, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care center at St. Francis
Hartford, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care center at Long Ridge
Long Ridge, Connecticut, United States
RECRUITINGYale Cancer Center at Yale University School of Medicine
New Haven, Connecticut, United States
RECRUITINGSmilow Cancer Hospital Care center at North Haven
North Haven, Connecticut, United States
RECRUITING...and 41 more locations
Time frame: Enrollment to end of treatment up to 1 year
Effects of therapy on work productivity
Evaluate effects of therapy on work productivity and activity using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP) in patients receiving trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel in combination with trastuzumab SC
Time frame: Enrollment to end of treatment up to 1 year
Effect of alopecia on patients
Evaluate the effects of alopecia on patients receiving paclitaxel in combination with trastuzumab SC using an alopecia questionnaire
Time frame: Enrollment to end of treatment up to 1 year
Incidence of Side Effects
Compare incidence of sensory neuropathy, headache, arthralgia and myalgia using PRO-CTCAE criteria in patients receiving trastuzumab emtansine followed by trastuzumab SC to that experienced by patients receiving paclitaxel in combination with trastuzumab SC
Time frame: Enrollment to end of treatment up to 1 year
Incidence of grade 3-4 cardiac left ventricular dysfunction
Evaluate the incidence of grade 3-4 cardiac left ventricular dysfunction in patients treated with adjuvant trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel with trastuzumab SC
Time frame: Enrollment to end of treatment up to 1 year
Incidence of trastuzumab-emtansine-induced grade 2-4 thrombocytopenia
Evaluate the 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
Investigate the percentage of patients with amenorrhea at various time points after the start of treatment in premenopausal women receiving treatment with trastuzumab emtansine followed by trastuzumab SC and paclitaxel with trastuzumab SC
Time frame: Enrollment to end of treatment up to 1 year
Evaluation of gene predictors of trastuzumab-emtansine-induced grade 2-4
Evaluate gene biomarkers predictive of trastuzumab-emtansine-induced grade 2-4 thrombocytopenia
Time frame: Enrollment to end of treatment up to 1 year
Gene Profiling
Utilize genomic profiling to query a large panel of cancer gene mutations and gene expression in patients with Stage I HER2-positive breast cancer
Time frame: Enrollment to end of treatment up to 1 year
Radiation therapy Toxicity
Evaluate the incidence of toxicities attributed to radiation therapy when given concurrently with trastuzumab SC after receipt of either trastuzumab emtansine or paclitaxel
Time frame: Enrollment to end of treatment up to 1 year
Overall survival
Describe overall survival in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine followed by trastuzumab SC
Time frame: Enrollment to end of treatment up to 1 year