ATOP TRIAL: T-DM1 in HER2 Positive Breast Cancer

NCT03587740 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-124
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 14

Brief Summary

This research study is studying an investigational drug as a possible treatment for breast cancer that is positive for the protein Human Epidermal Growth Factor Receptor 2, also known as HER2-positive breast cancer. The drug involved in this study is:

• ado-trastuzumab emtansine (T-DM1)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Invasive Disease-free Survival Rate (IDFS)

  IDFS is defined as the time from the first T-DM1 dose to ipsilateral invasive breast cancer recurrence, regional invasive breast cancer recurrence, distant recurrence, death due to any cause, contralateral invasive breast cancer, or a second non-breast primary cancer, whichever occurs first. Patients without one of these events at the time of data analysis will be censored at the date last known to be alive and event-free. Survival probabilities (reported as percentages) are estimated from Kaplan Meier methods.

  5 years

Secondary Outcomes (8)

• Invasive Breast Cancer-free Survival (IBCFS)

  5 years

• Recurrence-free Interval (RFI)

  5 years

• Overall Survival (OS)

  5 years

• Site of First Recurrence

  5 years

• Incidence Rate of All Toxicities (Safety)

  2 years

Study Arms (1)

T-DM1

EXPERIMENTAL

T-DM1 will be administered every 3 weeks intravenously, with 21 consecutive days defined as a treatment.

Drug: T-DM1

Interventions

T-DM1 DRUG

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.

Also known as: Kadcyla

T-DM1

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed HER2-positive disease by local pathology, defined as immunohistochemistry (IHC) 3+ or amplification by FISH (HER2/CEP17 ratio ≥2 or an average of ≥6 HER2 gene copies per nucleus) AND confirmed by Central Pathology Review (Dr. Deborah Dillon at Brigham and Women's Hospital, Boston, MA) prior to patient being registered to begin protocol therapy. See section 3.4. http://ascopubs.org/doi/full/10.1200/jco.2013.50.9984
• NOTE: DCIS components should not be counted in the determination of HER2 status.
• Age ≥60 years at the time of study registration (men and women eligible)
• Participants must have histologically or cytologically confirmed Stage I-III breast cancer with the following criteria met:
• If node-negative or if node status unknown (because it was not assessed), tumor must be \>5 mm of any hormone receptor subtype (document ER/PR status: if some ER/PR staining is present, ER and PR negative are defined as being positive in \<10% cells \[per local pathology read\]).
• If node-positive (N1-N3), T1mi, T1a, T1b, T1c, T2, or T3 tumors are eligible (see below for further details on defining node-negative disease) Definition of node-negative disease (when node status known): If the patient has had a negative sentinel node biopsy and/or a negative axillary dissection, then the patient is determined to be node-negative. Axillary nodes with single cells or tumor clusters ≤ 0.2 mm by either H\&E or IHC will be considered node-negative. Any axillary lymph node with tumor clusters between 0.02 and 0.2cm is considered a micrometastasis. Patients with a micrometastasis are eligible even if their tumor is \</= 5mm. An axillary dissection is not required to be performed in patients with a positive sentinel node and management of the axilla will be left up to the treating provider. 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. In these special situations, the investigator must document this approval in the patient medical record.
• ER/PR determination assays performed by IHC methods according to the local institution standard protocol.
• Standard chemotherapy/trastuzumab declined by patient OR patient is deemed by physician for any reason to not be a candidate for standard therapy (i.e. patient and/or provider choose not to pursue standard trastuzumab-based chemotherapy regimen because of concerns related to toxicity or provider/patient preference).
• For patients with bilateral or multifocal/multicentric breast cancers, one of the following criteria must be met to enroll: (1) each cancer individually meets criteria for enrollment (only ONE tumor has to undergo central confirmation for HER2), (2) at least one tumor meets eligibility (per tumor size/nodes/subtype outlined above) and the other foci in the ipsilateral or contralateral breast are also HER2-positive but are too small for enrollment (e.g., a patient is eligible if a cancer is T2N0 and HER2-positive in one breast, but the contralateral breast has a T1a HER2+ cancer that isn't eligible on its own, (3) there is at least one qualifying tumor of \>5mm but there are other small foci of disease that are too small to test for ER/PR/HER2 and are felt to be a part of the same tumor or similar tumor, OR (4) at least one tumor meets eligibility and the other foci in the ipsilateral or contralateral breast are HER2-negative and do not meet criteria for adjuvant chemotherapy per provider discretion (e.g. if a patient has a HER2-positive tumor meeting eligibility but also has a second, HER2-negative, small, node-negative, ER+, low grade cancer present, she is still eligible for enrollment). However, in the specific case that a second breast cancer is stage III and HER2-negative, that patient is excluded (because the second cancer is high-risk and likely will require non-HER2-directed therapy).
• All tumor removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy).
• NOTE: Management of axillary lymph nodes is up to the treating provider; however, all surgical 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.
• ≤90 days from the patient's most recent breast surgery for this breast cancer. Note: In cases where registration will occur \>90 days from surgery but within an acceptable time frame, patient may be eligible for enrollment with approval from the PI, Rachel Freedman MD, MPH.
• ECOG Performance Status (PS) 0-2. See Appendix F.
• Baseline ejection fraction ≥50% by MUGA scan or echocardiogram performed ≤60 days prior to registration.
• The following laboratory values obtained ≤14 days prior to registration:

You may not qualify if:

• Evidence of metastatic disease.
• Patients will not require baseline staging PET or CT chest, abdomen, pelvis or bone scan to rule out metastatic disease prior to enrollment. Any staging scans will be ordered at the treating provider's discretion. If metastatic disease is found on any staging studies done, patients will not be eligible for enrollment.
• Locally advanced tumors at diagnosis (T4), including tumors fixed to the chest wall, peau d'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid).
• Patients with stage III, HER2-negative cancer in the contralateral breast (see 3.1.6 above).
• Positive Hepatitis B (Hepatitis B surface antigen and antibody) and/or Hepatitis C (Hepatitis C antibody test) as indicated by serologies conducted ≤3 months prior to registration if liver function tests are outside of the normal institutional range.
• NOTE: A hepatitis panel is required of all participants as part of screening. Patients with positive Hepatitis B or C serologies indicating active infection without known active disease must meet the eligibility requirements for ALT, AST, total bilirubin, INR, PTT, and alkaline phosphatase on at least two consecutive occasions, separated by at least 1 week. Patients with laboratory evidence of vaccination to Hepatitis B (e.g., positive antibodies) are eligible.
• Active liver disease, for example, due to autoimmune hepatic disorder, or sclerosing cholangitis.
• Significant, active cardiopulmonary dysfunction (i.e. uncontrolled heart issues)as indicated by MUGA or echocardiogram performed ≤60 days prior to registration and/or by presence of any of the following:
• History of NCI CTCAE (Version 4.0) Grade ≥3 symptomatic congestive heart failure (CHF) or NYHA criteria Class ≥ II
• Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease
• High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate \> 100/min at rest, significant ventricular arrhythmia \[ventricular tachycardia\], or higher-grade atrioventricular \[AV\]-block \[second degree AV-block Type 2 \[Mobitz 2\] or third degree AV-block\]); if adequately and safely treated, patient may be eligible.
• Significant symptoms (Grade ≥ 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia
• Myocardial infarction within 12 months prior to registration
• Uncontrolled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \>100 mmHg)
• Evidence of transmural infarction on ECG

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Susan G. Komen Breast Cancer Foundation: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (14)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

The Stamford Hospital

Stamford, Connecticut, 06904, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute at St. Elizabeth's Medical Center

Brighton, Massachusetts, 02135, United States

Location

Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center

Milford, Massachusetts, 01757, United States

Location

Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Dana-Farber/New Hampshire Oncology-Hematology

Londonderry, New Hampshire, 03053, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Rex Cancer Center

Raleigh, North Carolina, 27607, United States

Location

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Rachel Freedman, MD, MPH
• Organization: Dana-Farber Cancer Institute

Rachel_Freedman@dfci.harvard.edu

617-632-3800

Study Officials

• Rachel Freedman, MD MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 21, 2018
• First Posted: July 16, 2018
• Study Start: August 22, 2018
• Primary Completion: March 3, 2025
• Study Completion (Estimated): August 30, 2027
• Last Updated: April 29, 2026
• Results First Posted: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)