Recruiting

Phase 2

T-DM1 vs. THATEMPT 2.0: Adjuvant T-DM1 vs TH

Sponsor:

Dana-Farber Cancer Institute

Code:

NCT04893109

Conditions

Breast Cancer

HER2-positive Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

trastuzumab-emtansine

Trastuzumab SC

Paclitaxel

Study Details

Brief 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

Conditions

Breast Cancer

HER2-positive Breast Cancer

Study ID

NCT04893109

Start date

Jun 16, 2021

Status verified date

Aug, 2026

Completion date

May 1, 2029

Anticipated

Primary completion date

Nov 1, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Patients must have HER2-positive Stage I histologically confirmed invasive carcinoma of the breast. Patients must have node-negative (N0) or micrometastases (N1mic) breast cancer according to the AJCC 8th edition anatomic staging table.

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:

Any of the following due to teratogenic potential of the study drugs:

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.

Study Design

Enrollment

500 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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

experimental: 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.

Interventions

trastuzumab-emtansine

intravenous infusion

Trastuzumab SC

Muscular injection

Paclitaxel

intravenous infusion

Primary outcome measure

Incidence of clinically relevant toxicities (CRT) [ Time Frame: First 18 weeks of treatment ]
Disease Free Survival (DFS) [ Time Frame: Time from randomization to first Disease Free Survival (DFS) event up to 72 months ]

Central Contacts and Locations

Central contacts

Sara Tolaney, MD, MPH

617-632-2335 sara_tolaney@dfci.harvard.edu

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

Recruiting

San Francisco, California, United States, 94158

Principal Investigator:

Hope Rugo, MD

Smilow Cancer Hospital Care center at Derby

Recruiting

Derby, Connecticut, United States, 06418

Contacts

Clinical Trial Offcie Yale Cancer Center

(203) 734-1664

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at Fairfield

Recruiting

Fairfield, Connecticut, United States, 06824

Contacts

Clinical Trials Office Yale Cancer Center

(203) 255-2766

Principal Investigator:

Daniel O'NEIL, MD

Smilow Cancer Hospital Care center at Glastonbury

Recruiting

Glastonbury, Connecticut, United States, 06033

Contacts

Clinical Trial Office Yale Cancer Center

(860) 714-9170

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at Greenwich

Recruiting

Greenwich, Connecticut, United States, 06830

Contacts

Clinical Trials Office Yale Cancer Center

(203) 863-3700

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at Guilford

Recruiting

Guilford, Connecticut, United States, 06437

Contacts

Clinical Trial Office Yale Cancer Center

(203) 453-9192

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at St. Francis

Recruiting

Hartford, Connecticut, United States, 06105

Contacts

Clinical Trial Office Yale Cancer Center

(860) 714-4680

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at Long Ridge

Recruiting

Long Ridge, Connecticut, United States, 06902

Contacts

Clinical Trial Office Yale Center

(203) 863-3700

Principal Investigator:

Daniel O'Neil, MD

Yale Cancer Center at Yale University School of Medicine

Recruiting

New Haven, Connecticut, United States, 06520-8028

Contacts

Clinical Trial Office Clinical Trials Office - Yale Cancer Center

203-785-5702

Principal Investigator:

Daniel O'Niel, MD

Smilow Cancer Hospital Care center at North Haven

Recruiting

North Haven, Connecticut, United States, 06510

Contacts

Clinical Trials Office Yale Cancer Center

(203) 407-8002

Principal Investigator:

Daniel O'neil, MD

Stamford Hospital

Recruiting

Stamford, Connecticut, United States, 06904

Contacts

K.M. Steve Lo, MD

slo@stamhealth.org

Principal Investigator:

K. M. Steve Lo, MD

Smilow Cancer Hospital Care center at Torrington

Recruiting

Torrington, Connecticut, United States, 06790

Contacts

Clinical Trial Office Yale Cancer Center

(860) 482-5384

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at Trumbull

Recruiting

Trumbull, Connecticut, United States, 06611

Contacts

Clinical Trials Office Cancer Trial

(203) 502-8400

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at Waterbury

Recruiting

Waterbury, Connecticut, United States, 06708

Contacts

Clinical Trials Office Yale Cancer Center

(203) 755-6311

Principal Investigator:

Daniel O'Neil, MD

Smilow Cancer Hospital Care center at Waterford

Recruiting

Waterford, Connecticut, United States, 06385

Contacts

Clinical Trials Office Yale Cancer Center

(860) 444-3744

Principal Investigator:

Daniel O'Neil, MD

Miami Cancer Institute/Baptist Hospital of Miami

Recruiting

Miami, Florida, United States, 33176

Miami Cancer Institute - Plantation (MCIP)

Recruiting

Plantation, Florida, United States, 33324

Contacts

Reshma Mahtani, DO

reshma.mahtani@baptisthealth.net

Principal Investigator:

Reshma Mahtani, DO

The University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Susan Cohn, MD

773-702-2571

Principal Investigator:

Nan Chen, MD

Eastern Maine Medical Center (Northern Light)

Recruiting

Brewer, Maine, United States, 04412

Contacts

Laurie Lewis

207-973-4249 llewis@northernlight.org

Principal Investigator:

Sarah J Sinclair, DO

New England Cancer Specialists

Recruiting

Scarborough, Maine, United States, 04074

Contacts

Rachael Farris

research@newecs.org

Principal Investigator:

Chiara Battelli, MD

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Sara M. Tolaney, MD MPH

617-632-2335 Sara_Tolaney@dfci.harvard.edu

Principal Investigator:

Sara M. Tolaney, MD MPH

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Laura Spring, MD

617-724-4000 Lspring2@partners.org

Principal Investigator:

Laura Spring, MD

Dana-Farber at St. Elizabeth's Medical Center

Recruiting

Brighton, Massachusetts, United States, 02135

Contacts

Wendy Loeser

Wendy_Loeser@DFCI.HARVARD.EDU

Principal Investigator:

Sara Giordano, MD

Lahey Clinic

Recruiting

Burlington, Massachusetts, United States, 01805

Contacts

Corrine Zarwan

781-744-8580 corrine.zarwan@lahey.org

Amanda Pietras

781-744-3495 amanda.pietras1@lahey.org

Principal Investigator:

Corrine Zarwan, MD

Mass General North Shore Cancer Center

Recruiting

Danvers, Massachusetts, United States, 01923

Contacts

Meegan Petersen

mpetersen1@partners.org

Principal Investigator:

Katherine Harris, MD

Dana-Farber Brigham Cancer Center - Foxborough

Recruiting

Foxborough, Massachusetts, United States, 02035

Contacts

Natalie Sinclair

781-624-4800 nsinclair1@partners.org

Principal Investigator:

Natalie Sinclair, MD

Dana-Farber Cancer Instiute - Merrimack Valley

Recruiting

Methuen, Massachusetts, United States, 01844

Contacts

Saida Hussein

saida_hussein@dfci.harvard.edu

Principal Investigator:

Pedro Sanz-Altamira, MD

Dana-Farber at Milford

Recruiting

Milford, Massachusetts, United States, 01757

Contacts

Natalie Sinclair, MD

NSINCLAIR1@PARTNERS.ORG

Principal Investigator:

Natalie Sinclair, MD

Newton Wellesley Hospital

Recruiting

Newton, Massachusetts, United States, 02462

Contacts

Natassia Mazzola

NAMAZZOLA@mgh.harvard.edu

Principal Investigator:

Aron Rosenstock, MD

Berkshire Medical Center

Recruiting

Pittsfield, Massachusetts, United States, 01201

Contacts

Lori O'Brien

lobrien@bhs1.org

Principal Investigator:

Thomas Fynan, MD

Dana Farber at South Shore Hospital

Recruiting

Weymouth, Massachusetts, United States, 02190

Contacts

Meredith Faggen

meredith_faggen@dfci.harvard.edu

7816244800

Principal Investigator:

Meredith Faggen, MD

NH Oncology-Hematology, PA - Payson Center for Cancer Care

Recruiting

Concord, New Hampshire, United States, 03301

Contacts

Ali Fleury

6032242556 a.fleury@nhoh.com

Principal Investigator:

Douglas Weckstein, MD

Dana-Farber Cancer Insitute at Londonderry Hospital

Recruiting

Londonderry, New Hampshire, United States, 03053

Contacts

Stefani Freeman, RN

StefaniD_Freeman@DFCI.HARVARD.EDU

Principal Investigator:

Jeanna Walsh, MD

Solinsky Center for Cancer Care (NH Oncology-Hematology, PA)

Recruiting

Manchester, New Hampshire, United States, 03103

Contacts

Ali Fleury

6032242556 a.fleury@nhoh.com

Principal Investigator:

Douglas Weckstein, MD

New England Cancer Specialists - Portsmouth

Recruiting

Portsmouth, New Hampshire, United States, 03801

Contacts

NECS Research

Research@newecs.org

Principal Investigator:

Chiara Battelli, MD

New York University Langone Hospital -Brooklyn

Recruiting

Brooklyn, New York, United States, 11220

Contacts

Breast Cancer Center

(718) 630-7000

Principal Investigator:

Nina D'Abreo, MD

New York University Langone Hospital - Long Island

Recruiting

Mineola, New York, United States, 11501

Contacts

Mehwash "Mahi" Muhammad

mehwash.muhammad@nyulangone.org

Principal Investigator:

Nina D'Abreo, MD

New York University Langone Health

Recruiting

New York, New York, United States, 10016

Contacts

Sylvia Adams, MD

sylvia.adams@nyulangone.org

Principal Investigator:

Nina D'Abreo, MD

Northwell University

Recruiting

New York, New York, United States, 10075

Contacts

Francisco Esteva

(855)-273-2789 festeva@northwell.edu

Principal Investigator:

Francisco Esteva

Stefanie Spielman Comprehensive Breast Center

Recruiting

Columbus, Ohio, United States, 43212

Contacts

Breast Cancer Clinical Trials

800-293-5066

Principal Investigator:

Gilbert Bader, MD

University of Pennsylvania, Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Igor Makhlin, MD

igor.makhlin@pennmedicine.upenn.edu

Principal Investigator:

Igor Makhlin, MD

University of Pittsburgh Medical Center Cancer UPMC- Magee Women's Hospital

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contacts

Marija Balic

412-647-2811 balicm@upmc.edu

Rometa Kerney

(412) 641-5430 pollardrr@upmc.edu

Principal Investigator:

Marija Balic, MD

Smilow Cancer Hospital Care center at Westerly

Recruiting

Westerly, Rhode Island, United States, 02891

Contacts

Clinical Trials Office Yale Cancer Center

(401) 656-4950

Principal Investigator:

Daniel O'Neil, MD

Greco-Hainsworth Centers for Research/Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

PJ Patterson

629-294-0801 ppatterson@tnonc.com

Principal Investigator:

Sara Nunnery, MD

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Lisa Simons

Lisa.Simons@scri.com

Principal Investigator:

Denise Yardley, MD

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Vicente Valero, MD

713 563 0751 vvalero@mdanderson.org

Principal Investigator:

Vicente Valero, MD

More Information

Sponsor

Dana-Farber Cancer Institute

Last update posted

Aug 19, 2026

Last verified

Aug, 2026

Keywords

Breast Cancer
HER2-positive Breast Cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Dana-Farber Cancer Institute on 2026-08-19.