Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
500 participants
INTERVENTIONAL
2021-06-16
2028-05-01
Brief Summary
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The name of the study drugs involved are:
* Trastuzumab-emtansine (T-DM1, Kadcyla)
* Trastuzumab SC (Herceptin Hylecta)
* Paclitaxel
Detailed Description
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* 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).
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A. T-DM1 followed by Trastuzumab SC
Randomized participants will receive intravenous T-DM1 every 3 weeks for 6 cycles (18 weeks) and then Trastuzumab SC (subcutaneous) every 3 weeks for 11 cycles
trastuzumab-emtansine
intravenous infusion
Trastuzumab SC
Muscular injection
Arm B: Paclitaxel with Trastuzumab SC, followed by Trastuzumab SC alone
Randomized participants will receive weekly intravenous Paclitaxel for 12 weeks (4 cycles) and Trastuzumab SC (subcutaneous) every 3 weeks for 17 cycles. The first 4 doses Trastuzumab SC are given with Paclitaxel.
Trastuzumab SC
Muscular injection
Paclitaxel
intravenous infusion
Interventions
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trastuzumab-emtansine
intravenous infusion
Trastuzumab SC
Muscular injection
Paclitaxel
intravenous infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative. If an axillary dissection without sentinel lymph node biopsy is performed to determine nodal status, at least six axillary lymph nodes must be removed and analyzed, and determined to be negative, for the patient to be considered node-negative. Axillary nodes with single cells or tumor clusters ≤ 0.2 mm by either H\&E or immunohistochemistry (IHC) will be considered node-negative.
* Any axillary lymph node with tumor clusters between 0.02 and 0.2 cm is considered a micrometastasis. Patients with a micrometastasis are eligible. An axillary dissection is not required to be performed in patients with a micrometastasis found by sentinel node evaluation. In cases where the specific pathologic size of lymph node involvement is subject to interpretation, the principal investigator will make the final determination as to eligibility. The investigator must document approval in the patient medical record.
* Patients who have an area of a T1aN0, ER+ (defined as \>10%), HER2-negative cancer in addition to their primary HER2-positive tumor are eligible.
* HER2-positive by ASCO CAP 2018 guidelines, confirmed by central testing. NOTE: HER-2 status must be confirmed to be positive by central review by NeoGenomics prior to patient starting protocol therapy. Patients previously having had HER2 immunohistochemical testing by NeoGenomics do not need to undergo retesting for central confirmation of HER2 status.
NOTE: DCIS components will not be counted in the determination of HER2 status
* ER/PR determination is required. ER and PR assays should be performed by immunohistochemical methods according to the local institution standard protocol.
* Bilateral breast cancers that individually meet eligibility criteria are allowed.
* Patients with multifocal or multicentric disease are eligible, as long as each tumor individually meets eligibility criteria. Central confirmation is needed for any site of disease that is tested to be HER2-positive by local testing (unless testing was previously done by NeoGenomics).
* Patients with a history of ipsilateral DCIS are eligible if they were treated with wide excision alone, without radiation therapy, or treated with a mastectomy for this current breast cancer. Patients with a history of contralateral DCIS are not eligible.
* ≤ 90 days between the planned treatment start date and the patient's most recent breast surgery for this breast cancer
* ≥ 18 years of age with any menopausal status.
* ECOG Performance Status 0 or 1
* All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy), with either a sentinel node biopsy or axillary dissection
* All margins should be clear of invasive cancer or DCIS (i.e. no tumor on ink). The local pathologist must document negative margins of resection in the pathology report. If all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed. Likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed.
* Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy. Radiation to the conserved breast is required.
* Patients may have received up to 4 weeks of tamoxifen therapy, or other hormonal therapy, for adjuvant therapy for this cancer. Patients cannot receive adjuvant hormonal therapy during protocol treatment for the first 12 weeks.
* Prior oophorectomy for cancer prevention is allowed.
* Patients who have undergone partial breast radiation (duration ≤ 14 days) prior to registration are eligible. Partial breast radiation must be completed prior to 2 weeks before starting protocol therapy. Patients who have undergone whole breast radiation are not eligible.
* Patients who have participated in a window study (treatment with an investigational agent prior to surgery for ≤ 2 weeks) are eligible. Patients must have discontinued the investigational agent at least 14 days before participation.
* Adequate bone marrow function:
* ANC ≥ 1000/mm3,
* Hemoglobin ≥ 9 g/dl
* Platelets ≥ 100,000/mm3
* Adequate hepatic function:
* Total bilirubin ≤ 1.2mg/dL
* AST and ALT ≤ 1.5x Institutional ULN
* For patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range. Serum alkaline phosphatase should be ≤ 1.5x Institutional ULN.
* Left ventricular ejection fraction (LVEF) ≥ 50%
* Premenopausal patients must have a negative serum or urine pregnancy test, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause.
* Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of nonhormonal contraception or two effective forms of nonhormonal contraception by the patient and/or partner. Contraceptive use must be continued for the duration of the study treatment and for 7 months after the last dose of study treatment. Hormonal birth control methods are not permitted.
* Patients should have tumor tissue available, and a tissue block of sufficient size to make 15 slides, which must be sent to DFCI for correlative research. If a tissue block is unavailable, sites may send one H\&E-stained slide and 15 unstained sections of paraffin-embedded tissue on uncharged slides. Slide sections should be 4-5 microns in thickness. It is also acceptable to submit 2 cores from a block of invasive tissue using a 1.2 mm diameter coring tool. If tumor is not available, the investigator must document why tissue is not available in the patient medical record, and that efforts have been made to obtain tissue.
* Willing and able to sign informed consent
* Must be able to read and understand English in order to participate in the quality of life surveys. If patient does not read and understand English, the patient is still eligible, but cannot participate in the quality of life surveys.
Exclusion Criteria
* Pregnant women
* Nursing women
* Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, IUDs, surgical sterilization, abstinence, etc.).
* Men who are unwilling to employ adequate contraception (condoms, surgical sterilization, abstinence, etc.).
* Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
* Patients with a history of previous invasive breast cancer.
* History of prior chemotherapy in the past 5 years.
* History of paclitaxel therapy
* Patients with active liver disease, for example due to hepatitis B virus, hepatitis C virus, autoimmune hepatic disorder, or sclerosing cholangitis
* Individuals with a history of a different malignancy are ineligible except for the following circumstances:
* Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy.
* Individuals with the following cancer are eligible regardless of when they were diagnosed and treated: cervical cancer in situ, and non-melanoma cancer of the skin.
* Intercurrent illness including, but not limited to: ongoing or active, unresolved systemic infection, renal failure requiring dialysis, active cardiac disease, prior myocardial infarction (asymptomatic changes on EKG suggestive of old MI is not an exclusion), history of CHF, current use of any therapy specifically for CHF, uncontrolled hypertension, significant psychiatric illness, or other conditions that in the opinion of the investigator limit compliance with study requirements.
18 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
Dana-Farber Cancer Institute
OTHER
Responsible Party
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Sara Tolaney, MD
Principal Investigator
Principal Investigators
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Sara Tolaney, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Dana-Farber Cancer Institute
Locations
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UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Smilow Cancer Hospital Care center at Derby
Derby, Connecticut, United States
Smilow Cancer Hospital Care center at Fairfield
Fairfield, Connecticut, United States
Smilow Cancer Hospital Care center at Glastonbury
Glastonbury, Connecticut, United States
Smilow Cancer Hospital Care center at Greenwich
Greenwich, Connecticut, United States
Smilow Cancer Hospital Care center at Guilford
Guilford, Connecticut, United States
Smilow Cancer Hospital Care center at St. Francis
Hartford, Connecticut, United States
Smilow Cancer Hospital Care center at Long Ridge
Long Ridge, Connecticut, United States
Yale Cancer Center at Yale University School of Medicine
New Haven, Connecticut, United States
Smilow Cancer Hospital Care center at North Haven
North Haven, Connecticut, United States
Stamford Hospital
Stamford, Connecticut, United States
Smilow Cancer Hospital Care center at Torrington
Torrington, Connecticut, United States
Smilow Cancer Hospital Care center at Trumbull
Trumbull, Connecticut, United States
Smilow Cancer Hospital Care center at Waterbury
Waterbury, Connecticut, United States
Smilow Cancer Hospital Care center at Waterford
Waterford, Connecticut, United States
Miami Cancer Institute/Baptist Hospital of Miami
Miami, Florida, United States
Miami Cancer Institute - Plantation (MCIP)
Plantation, Florida, United States
The University of Chicago Medical Center
Chicago, Illinois, United States
Indiana University Health Joe & Shelly Schwarz Cancer Center
Carmel, Indiana, United States
IU Health North Hospital
Carmel, Indiana, United States
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, United States
Indiana University Sidney and Lois Eskenazi Hospital
Indianapolis, Indiana, United States
Eastern Maine Medical Center (Northern Light)
Brewer, Maine, United States
New England Cancer Specialists
Scarborough, Maine, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana-Farber at St. Elizabeth's Medical Center
Brighton, Massachusetts, United States
Mass General North Shore Cancer Center
Danvers, Massachusetts, United States
Dana-Farber Brigham Cancer Center - Foxborough
Foxborough, Massachusetts, United States
Dana-Farber Cancer Instiute - Merrimack Valley
Methuen, Massachusetts, United States
Dana-Farber at Milford
Milford, Massachusetts, United States
Newton Wellesley Hospital
Newton, Massachusetts, United States
Berkshire Medical Center
Pittsfield, Massachusetts, United States
Dana Farber at South Shore Hospital
Weymouth, Massachusetts, United States
NH Oncology-Hematology, PA - Payson Center for Cancer Care
Concord, New Hampshire, United States
Dana-Farber Cancer Insitute at Londonderry Hospital
Londonderry, New Hampshire, United States
Solinsky Center for Cancer Care (NH Oncology-Hematology, PA)
Manchester, New Hampshire, United States
New England Cancer Specialists - Portsmouth
Portsmouth, New Hampshire, United States
New York University Langone Hospital -Brooklyn
Brooklyn, New York, United States
New York University Langone Hospital - Long Island
Mineola, New York, United States
New York University Langone Health
New York, New York, United States
Northwell University
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Duke Women's Cancer Care Raleigh
Raleigh, North Carolina, United States
Stefanie Spielman Comprehensive Breast Center
Columbus, Ohio, United States
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Smilow Cancer Hospital Care center at Westerly
Westerly, Rhode Island, United States
Greco-Hainsworth Centers for Research/Tennessee Oncology
Nashville, Tennessee, United States
SCRI Oncology Partners
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
Countries
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Central Contacts
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Facility Contacts
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Hope Rugo, MD
Role: primary
Clinical Trial Offcie Yale Cancer Center
Role: primary
Clinical Trials Office Yale Cancer Center
Role: primary
Clinical Trial Office Yale Cancer Center
Role: primary
Clinical Trials Office Yale Cancer Center
Role: primary
Clinical Trial Office Yale Cancer Center
Role: primary
Clinical Trial Office Yale Cancer Center
Role: primary
Clinical Trial Office Yale Center
Role: primary
Clinical Trial Office Clinical Trials Office - Yale Cancer Center
Role: primary
Clinical Trials Office Yale Cancer Center
Role: primary
K.M. Steve Lo, MD
Role: primary
Clinical Trial Office Yale Cancer Center
Role: primary
Clinical Trials Office Cancer Trial
Role: primary
Clinical Trials Office Yale Cancer Center
Role: primary
Clinical Trials Office Yale Cancer Center
Role: primary
Reshma Mahtani, DO
Role: primary
Reshma Mahtani, DO
Role: primary
Susan Cohn, MD
Role: primary
Laurie Lewis
Role: primary
Rachael Farris
Role: primary
Nadine Tung, MD
Role: primary
Sara M. Tolaney, MD MPH
Role: primary
Laura Spring, MD
Role: primary
Wendy Loeser
Role: primary
Meegan Petersen
Role: primary
Natalie Sinclair
Role: primary
Saida Hussein
Role: primary
Natalie Sinclair, MD
Role: primary
Natassia Mazzola
Role: primary
Lori O'Brien
Role: primary
Meredith Faggen
Role: primary
Role: backup
Ali Fleury
Role: primary
Stefani Freeman, RN
Role: primary
Ali Fleury
Role: primary
NECS Research
Role: primary
Breast Cancer Center
Role: primary
Mehwash "Mahi" Muhammad
Role: primary
Sylvia Adams, MD
Role: primary
Francisco Esteva
Role: primary
Breast Cancer Clinical Trials
Role: primary
Igor Makhlin, MD
Role: primary
Clinical Trials Office Yale Cancer Center
Role: primary
PJ Patterson
Role: primary
Lisa Simons
Role: primary
Vicente Valero, MD
Role: primary
Other Identifiers
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21-159
Identifier Type: -
Identifier Source: org_study_id