RECRUITING

ATEMPT 2.0: Adjuvant T-DM1 Vs TH

Conditions

Breast Cancer HER2-positive Breast Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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)

Quick Facts

Study Start:2021-06-16

Study Completion:2028-05-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04893109

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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.	* 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.

Inclusion Criteria

Exclusion 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.
* 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.

* 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.

Contacts and Locations

Study Contact

Sara Tolaney, MD, PhD

CONTACT

617-632-2335

sara_tolaney@dfci.harvard.edu

Principal Investigator

Sara Tolaney, MD, PhD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158

United States

Smilow Cancer Hospital Care center at Derby

Derby, Connecticut, 06418

United States

Smilow Cancer Hospital Care center at Fairfield

Fairfield, Connecticut, 06824

United States

Smilow Cancer Hospital Care center at Glastonbury

Glastonbury, Connecticut, 06033

United States

Smilow Cancer Hospital Care center at Greenwich

Greenwich, Connecticut, 06830

United States

Smilow Cancer Hospital Care center at Guilford

Guilford, Connecticut, 06437

United States

Smilow Cancer Hospital Care center at St. Francis

Hartford, Connecticut, 06105

United States

Smilow Cancer Hospital Care center at Long Ridge

Long Ridge, Connecticut, 06902

United States

Yale Cancer Center at Yale University School of Medicine

New Haven, Connecticut, 06520-8028

United States

Smilow Cancer Hospital Care center at North Haven

North Haven, Connecticut, 06510

United States

Stamford Hospital

Stamford, Connecticut, 06904

United States

Smilow Cancer Hospital Care center at Torrington

Torrington, Connecticut, 06790

United States

Smilow Cancer Hospital Care center at Trumbull

Trumbull, Connecticut, 06611

United States

Smilow Cancer Hospital Care center at Waterbury

Waterbury, Connecticut, 06708

United States

Smilow Cancer Hospital Care center at Waterford

Waterford, Connecticut, 06385

United States

Miami Cancer Institute/Baptist Hospital of Miami

Miami, Florida, 33176

United States

Miami Cancer Institute - Plantation (MCIP)

Plantation, Florida, 33324

United States

Indiana University Health Joe & Shelly Schwarz Cancer Center

Carmel, Indiana, 46032

United States

IU Health North Hospital

Carmel, Indiana, 46032

United States

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202

United States

Indiana University Sidney and Lois Eskenazi Hospital

Indianapolis, Indiana, 46202

United States

Eastern Maine Medical Center (Northern Light)

Brewer, Maine, 04412

United States

New England Cancer Specialists

Scarborough, Maine, 04074

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Massachusetts General Hospital

Boston, Massachusetts, 02215

United States

Dana-Farber at St. Elizabeth's Medical Center

Brighton, Massachusetts, 02135

United States

Mass General North Shore Cancer Center

Danvers, Massachusetts, 01923

United States

Dana-Farber Brigham Cancer Center - Foxborough

Foxborough, Massachusetts, 02035

United States

Dana-Farber Cancer Instiute - Merrimack Valley

Methuen, Massachusetts, 01844

United States

Dana-Farber at Milford

Milford, Massachusetts, 01757

United States

Newton Wellesley Hospital

Newton, Massachusetts, 02462

United States

Berkshire Medical Center

Pittsfield, Massachusetts, 01201

United States

Dana Farber at South Shore Hospital

Weymouth, Massachusetts, 02190

United States

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

Concord, New Hampshire, 03301

United States

Dana-Farber Cancer Insitute at Londonderry Hospital

Londonderry, New Hampshire, 03053

United States

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

Manchester, New Hampshire, 03103

United States

New England Cancer Specialists - Portsmouth

Portsmouth, New Hampshire, 03801

United States

New York University Langone Hospital -Brooklyn

Brooklyn, New York, 11220

United States

New York University Langone Hospital - Long Island

Mineola, New York, 11501

United States

New York University Langone Health

New York, New York, 10016

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Duke Women's Cancer Care Raleigh

Raleigh, North Carolina, 27710

United States

Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212

United States

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

United States

Smilow Cancer Hospital Care center at Westerly

Westerly, Rhode Island, 02891

United States

SCRI Oncology Partners

Nashville, Tennessee, 37203

United States

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Dana-Farber Cancer Institute

Sara Tolaney, MD, PhD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-06-16

Study Completion Date2028-05-01

Study Record Updates

Study Start Date2021-06-16

Study Completion Date2028-05-01

Terms related to this study

Keywords Provided by Researchers

Breast Cancer
HER2-positive Breast Cancer

Additional Relevant MeSH Terms

Breast Cancer
HER2-positive Breast Cancer