T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)

NCT ID: NCT01853748

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 512 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2025-12-31

Brief Summary

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not approved this drug for use patients undergoing adjuvant treatment for HER2+ breast cancer. Trastuzumab emtansine (T-DM1) is a drug that may stop cancer cells from growing. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to prevent the recurrence of breast cancer in this research study.

The use of T-DM1 in this research study is experimental, which means it is not approved by any regulatory authority for the adjuvant treatment of HER2-positive breast cancer. However, it FDA-approved for metastatic HER2-positive breast cancer. T-DM1 has caused cancer cells to die in laboratory studies. In preclinical studies, this drug has prevented or slowed the growth of breast cancer. The breast cancer treatments (paclitaxel and Trastuzumab) used in this study are considered part of standard-of-care regimens in early breast cancer. A standard treatment means that this is a treatment that would be accepted by the majority of the medical community as a suitable treatment for your type of breast cancer.

In this research study, the investigators are looking to see if the study drug T-DM1 will have less side effects than traditional HER2-positive breast cancer treatment of trastuzumab and paclitaxel. The investigators are also hoping to learn about the long term benefits and disease-free survival of participants who take the study drug T-DM1 in comparison to those participants to take the combination of trastuzumab and paclitaxel.

Detailed Description

If a participant agrees to participate in this study she will be asked to undergo some screening tests or procedures to confirm that she is eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if turns out that she does not take part in this research study. If she has had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures will include: a medical history, performance status, assessment of your tumor, blood tests, cardiac tests, pregnancy test and a collection of tumor tissue. If these tests show that she is eligible to participate in the research study, she will begin the study treatment. If she does not meet the eligibility criteria, she will not be able to participate in this research study.

Because no one knows which of the study options is best, the participant will be "randomized" into one of the study groups after she has had her breast surgery: Group 1 or Group 2. Randomization means that she is put into a group by chance. Neither the participant nor the research doctor will choose what group she will be in. The participant will have a one in three chance of being placed in any group. Approximately 375 study participants will receive the study drug, while 125 study participants will receive the standard therapy of trastuzumab and paclitaxel.

Group 1 participants will receive the study drug T-DM1 every three weeks by IV (intravenous injection) for 17 treatments (total of 51 weeks).

Group 2 participants will receive the FDA-approved drugs Paclitaxel and Trastuzumab once per week by IV for 12 weeks. Then beginning week 13, participants will receive Trastuzumab only by IV injection every three weeks for the next 13 treatments.

During all cycles the participant will have a physical exam and tumor assessment.

The investigators would like to keep track of the participant's medical condition for the next five years after the final dose of study drug. The investigators would like to do this by regular visits every 6 months for 3 years after completion of study treatment, and then once a year for the next two years. The investigators may ask for additional follow-up by phone after completion of these visits.

Participants who undergo lumpectomy (breast conserving surgery) need to receive breast radiation therapy to participate in this study. Participants who have undergone a mastectomy may receive chest wall and lymph node radiation (as determined by discussion with their physician). Radiation Therapy will begin after the conclusion of all study paclitaxel doses, and after 12 weeks fo the study drug T-DM1.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trastuzumab emtansine (T-DM1)

T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks

Group Type: ACTIVE_COMPARATOR

Trastuzumab emtansine

Intervention Type: DRUG

Paclitaxel + Trastuzumab

paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Interventions

Trastuzumab

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Trastuzumab emtansine

Intervention Type: DRUG

Other Intervention Names

T-DM1

Eligibility Criteria

Inclusion Criteria

• HER2-positive Stage I histologically confirmed invasive carcinoma of the breast
• ER/PR determination is required
• HER2 positive, confirmed by central testing: IHC 3+, FISH HER2/CEP17 <2.0 with an average HER2 copy number >/=6.0, or FISH HER2/CEP17 >/= 2.0
• Bilateral breast cancers that individually meet eligibility criteria are allowed
• Subjects with multifocal or multicentric disease are eligible as long as each tumor individually meets eligibility criteria
• Subjects with a history of ipsilateral DCIS are eligible if they were treated with wide-excision alone, without radiation therapy; Patients with a history of contralateral DCIS are not eligible.
• Should have tumor tissue available and a tissue block of sufficient size to make 15 slides, which must be sent to a DFCI site for testing
• Less than or equal to 90 days since most recent breast surgery for this breast cancer
• 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
• May have received up to 4 weeks of tamoxifen therapy or other hormonal therapy, for adjuvant therapy for this cancer
• Prior oophorectomy for cancer prevention is allowed
• Subjects who have undergone partial breast radiation (duration </= 7 days) prior to registration are eligible. Partial breast radiation must be completed prior to 2 weeks before starting protocol therapy.
• Must have discontinued any investigational drug at least 2 weeks prior to participation
• Willing to use one highly effective from of nonhormonal contraception or two effective forms of nonhormonal contraception while on study and for 7 months after end of study treatment
• Subjects undergoing lumpectomy must have no contraindications to radiation therapy

Exclusion Criteria

• Pregnant or breastfeeding
• Use of potent CYP3A4 inhibitors during the study treatment period
• Excessive alcohol intake (more than 3 alcoholic beverages per day)
• Locally advanced tumors at diagnosis
• History of previous invasive breast cancer
• History of prior chemotherapy in the past 5 years
• History of prior trastuzumab or prior paclitaxel therapy
• Active, unresolved infection
• Active liver disease
• History of a different malignancy except for the following: disease free for at least 5 years and at low risk for recurrence; cervical cancer in situ, basal or squamous cell carcinoma of the skin
• Active cardiac disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Sara Tolaney, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sara Tolaney, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

University of Alabama Birmingham

Birmingham, Alabama, United States

University of California San Francisco

San Francisco, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Midstate Medical Center

Meriden, Connecticut, United States

Hartford Healthcare Cancer Institute at The Hospital of Central Connecticut

New Britain, Connecticut, United States

William W Backus Hospital

Norwich, Connecticut, United States

Georgetown Hospital

Washington D.C., District of Columbia, United States

Washington Cancer Institute at Medstar Washington Hospital Center

Washington D.C., District of Columbia, United States

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Florida Cancer Specialists

St. Petersburg, Florida, United States

Mountain States Tumor Institute

Boise, Idaho, United States

Mountain States Tumor Institute

Fruitland, Idaho, United States

Mountain States Tumor Institute

Meridian, Idaho, United States

Mountain States Tumor Institute

Nampa, Idaho, United States

Mountain States Tumor Institute

Twin Falls, Idaho, United States

Loyola University Medical Center

Maywood, Illinois, United States

University of Chicago Comprehensive Cancer Center at Silver Cross Hospital

New Lenox, Illinois, United States

University of Chicago Medical Center for Advanced Care Orland Park

Orland Park, Illinois, United States

Indiana University - Wishard Hospital

Indianapolis, Indiana, United States

Indiana University Health - Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Indiana University Health - University Hospital

Indianapolis, Indiana, United States

Indiana University - Springmill Medical Clinic

Indianapolis, Indiana, United States

Eastern Maine Medical Center's Cancer Care

Brewer, Maine, United States

Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Suburban Hospital Cancer Program

Bethesda, Maryland, United States

Johns Hopkins - Green Spring Station

Lutherville, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute at Faulkner Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Mass General North Shore Cancer Center

Danvers, Massachusetts, United States

Lowell General Hospital

Lowell, Massachusetts, United States

Dana-Farber Cancer Institute at Milford Hospital

Milford, Massachusetts, United States

Univeristy of Michigan Health System

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Siteman Cancer Center - St. Peters

City of Saint Peters, Missouri, United States

Barnes-Jewish Hospital

St Louis, Missouri, United States

Washington University, School of Medicine

St Louis, Missouri, United States

Siteman Cancer Center - South County

St Louis, Missouri, United States

Siteman Cancer Center - West County

St Louis, Missouri, United States

New Hampshire Oncology-Hematology, PA

Concord, New Hampshire, United States

New Hampshire Oncology-Hematology, PA

Hooksett, New Hampshire, United States

New Hampshire Oncology-Hematology, PA

Laconia, New Hampshire, United States

Dana-Farber Cancer Insitute at Londonderry Hospital

Londonderry, New Hampshire, United States

Memorial Sloan Kettering Cancer Center-Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Cancer Center-Suffolk

Commack, New York, United States

Memorial Sloan Kettering Cancer Center Westchester

Harrison, New York, United States

Queens Hospital Center, Comprehensive Cancer Center

Jamaica, New York, United States

Northwell Health/Monter Cancer Center

Lake Success, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center-Mercy

Rockville Centre, New York, United States

Memorial Sloan Kettering Cancer Center-Sleepy Hollow

Sleepy Hollow, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Rex Cancer Center

Raleigh, North Carolina, United States

The Ohio State University

Columbus, Ohio, United States

Lehigh Valley Hospital/Lehigh Valley Health Network

Allentown, Pennsylvania, United States

UPMC/HVHS Cancer Center, UPMC Beaver

Beaver, Pennsylvania, United States

UPMC CancerCenters Butler

Butler, Pennsylvania, United States

UPMC Horizon (Shenango)

Farrell, Pennsylvania, United States

Arnold Palmer Cancer Center-Greensburg

Greensburg, Pennsylvania, United States

Arnold Palmer Medical Oncology Oakbrook

Greensburg, Pennsylvania, United States

UPMC Horizon (Greenville)

Greenville, Pennsylvania, United States

UPMC Pinnacle Harrisburg

Harrisburg, Pennsylvania, United States

UPMC Cancer Center Jefferson Regional Med Ctr

Jefferson Hills, Pennsylvania, United States

UPMC Conemaugh Cancer Center

Johnstown, Pennsylvania, United States

UPMC McKeesport

McKeesport, Pennsylvania, United States

UPMC East

Monroeville, Pennsylvania, United States

Arnold Palmer Medical Oncology-Mt Pleasant

Mount Pleasant, Pennsylvania, United States

UPMC Jameson Cancer Center

New Castle, Pennsylvania, United States

UPMC St. Margaret

Pittsburgh, Pennsylvania, United States

UPMC Cancer Center St. Clair Hospital

Pittsburgh, Pennsylvania, United States

UPMC Presbyterian Shadyside

Pittsburgh, Pennsylvania, United States

UPMC Passavant

Pittsburgh, Pennsylvania, United States

UPMC Northwest (Franklin)

Seneca, Pennsylvania, United States

UPMC Northwest (Oil City)

Seneca, Pennsylvania, United States

UPMC and the Washington Hospital Center

Washington, Pennsylvania, United States

Tennessee Oncology/Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Baylor College of Medicine-Baylor Clinic

Houston, Texas, United States

Harris County Hospital District-Ben Taub General Hospital

Houston, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Harris County Hospital District-Smith Clinic

Houston, Texas, United States

University of Washington Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

References

Tarantino P, Tayob N, Villacampa G, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Garrett AM, Marcom PK, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu MC, Ruddy KJ, Waks AG, DeMeo M, Burstein HJ, Partridge AH, Dell'Orto P, Russo L, Krause E, Newhouse DJ, Kurt BB, Mittendorf EA, Schneider B, Prat A, Winer EP, Krop IE, Tolaney SM; Consortium of the TBCRC Translational Investigators; TBCRC Translational Investigators. Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT. J Clin Oncol. 2024 Nov;42(31):3652-3665. doi: 10.1200/JCO.23.02170. Epub 2024 Jun 27.

Reference Type: DERIVED

PMID: 38935923 (View on PubMed)

Sella T, Zheng Y, Tayob N, Ruddy KJ, Freedman RA, Dang C, Yardley D, Isakoff SJ, Valero V, DeMeo M, Burstein HJ, Winer EP, Wolff AC, Krop I, Partridge AH, Tolaney SM. Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT). NPJ Breast Cancer. 2022 Nov 30;8(1):127. doi: 10.1038/s41523-022-00495-x.

Reference Type: DERIVED

PMID: 36450763 (View on PubMed)

Barroso-Sousa R, Tarantino P, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy KJ, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I, Tolaney SM. Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial. NPJ Breast Cancer. 2022 Feb 16;8(1):18. doi: 10.1038/s41523-022-00385-2.

Reference Type: DERIVED

PMID: 35173164 (View on PubMed)

Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. J Clin Oncol. 2021 Jul 20;39(21):2375-2385. doi: 10.1200/JCO.20.03398. Epub 2021 Jun 2.

Reference Type: DERIVED

PMID: 34077270 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

13-048

Identifier Type: -

Identifier Source: org_study_id