Clinical trial NCT01853748: T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)
Official title: A Randomized Phase II Study of Trastuzumab Emtansine (T-DM1) vs. Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT Trial)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2013-05-15
Enrollment: 512
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants of Clinically Relevant Toxicities (CRT)
timeFrame: 5 years after completion of study treatment or until death, whichever occurs first.
measure: 3-year Disease Free Survival (DFS) Rate of Trastuzumab Emtansine (TDM-1)
timeFrame: 3 years
Secondary outcomes:
measure: Incidence Rate of Grade 3-4 Treatment-Related Toxicity
timeFrame: AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.
measure: Quality of Life (QOL) FACT B Total Score at Baseline
timeFrame: at baseline
measure: Quality of Life (QOL) FACT B Total Score at Week 3
timeFrame: at week 3
measure: Quality of Life (QOL) FACT B Total Score at Week 12
timeFrame: at week 12
measure: Quality of Life (QOL) FACT B Total Score at 6 Months
timeFrame: at 6 months
measure: Quality of Life (QOL) FACT B Total Score at 1 Year
timeFrame: at 1 year
measure: Quality of Life (QOL) FACT B Total Score at 18 Months
timeFrame: at 18 months
measure: Quality of Life (QOL) FACT B Total Score at 24 Months
timeFrame: at 24 months
measure: Number of Patients Has Neuropathy
timeFrame: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18. The data cutoff date is 18 month.
measure: Percentage of Work Time Missed Because of Health
timeFrame: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.
measure: Percentage of Impairment While Working Because of Health (Mean, SD)
timeFrame: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.
measure: Percentage of Overall Work Impairment Because of Health
timeFrame: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.
measure: Percentage of Activity Impairment Because of Health
timeFrame: Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.
measure: Number of Patients Have Alopecia
timeFrame: Median follow-up was 3.9 years. The AE data cutoff date is 21 April 2020.
measure: 3-year T-DM1 iDFS Percentage by Tumor Size and Hormone Receptor (HR) Status
timeFrame: 3 years
measure: Number of Incidence of Grade 3-4 Cardiac Left Ventricular Dysfunction
timeFrame: AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.
measure: Number of Incidence of T-DM1 Induced Grade 2-3 Thrombocytopenia
timeFrame: AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.
measure: Number of SNPs With Top Associations of Trastuzumab Emtansine-induced Grade 2-4 Thrombocytopenia in the T-DM1 Arm
timeFrame: DNA sample collected at pre-treatment. AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks.
measure: Percentage of Patients With Amenorrhea
timeFrame: Surveys are took at month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.
measure: Gene Mutation Assessed Using High-throughput Mutation Profiling System (Oncomap)
timeFrame: After treatment
measure: Median Overall Survival (OS)
timeFrame: Reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Meriden
country: United States
facility: Midstate Medical Center
state: Connecticut
city: New Britain
country: United States
facility: Hartford Healthcare Cancer Institute at The Hospital of Central Connecticut
state: Connecticut
city: Norwich
country: United States
facility: William W Backus Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown Hospital
state: District of Columbia
city: Washington
country: United States
facility: Washington Cancer Institute at Medstar Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boise
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Fruitland
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Meridian
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Nampa
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Twin Falls
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: New Lenox
country: United States
facility: University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Orland Park
country: United States
facility: University of Chicago Medical Center for Advanced Care Orland Park
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University - Wishard Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health - Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health - University Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University - Springmill Medical Clinic
state: Indiana
city: Brewer
country: United States
facility: Eastern Maine Medical Center's Cancer Care
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital Cancer Program
state: Maryland
city: Lutherville
country: United States
facility: Johns Hopkins - Green Spring Station
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute at Faulkner Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Danvers
country: United States
facility: Mass General North Shore Cancer Center
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Milford
country: United States
facility: Dana-Farber Cancer Institute at Milford Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Univeristy of Michigan Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University, School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St. Peters
state: Missouri
city: Concord
country: United States
facility: New Hampshire Oncology-Hematology, PA
state: New Hampshire
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology, PA
state: New Hampshire
city: Laconia
country: United States
facility: New Hampshire Oncology-Hematology, PA
state: New Hampshire
city: Londonderry
country: United States
facility: Dana-Farber Cancer Insitute at Londonderry Hospital
state: New Hampshire
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center-Basking Ridge
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center-Suffolk
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center Westchester
state: New York
city: Jamaica
country: United States
facility: Queens Hospital Center, Comprehensive Cancer Center
state: New York
city: Lake Success
country: United States
facility: Northwell Health/Monter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Cancer Center-Mercy
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan Kettering Cancer Center-Sleepy Hollow
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Hospital/Lehigh Valley Health Network
state: Pennsylvania
city: Beaver
country: United States
facility: UPMC/HVHS Cancer Center, UPMC Beaver
state: Pennsylvania
city: Butler
country: United States
facility: UPMC CancerCenters Butler
state: Pennsylvania
city: Farrell
country: United States
facility: UPMC Horizon (Shenango)
state: Pennsylvania
city: Greensburg
country: United States
facility: Arnold Palmer Cancer Center-Greensburg
state: Pennsylvania
city: Greensburg
country: United States
facility: Arnold Palmer Medical Oncology Oakbrook
state: Pennsylvania
city: Greenville
country: United States
facility: UPMC Horizon (Greenville)
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Pinnacle Harrisburg
state: Pennsylvania
city: Jefferson Hills
country: United States
facility: UPMC Cancer Center Jefferson Regional Med Ctr
state: Pennsylvania
city: Johnstown
country: United States
facility: UPMC Conemaugh Cancer Center
state: Pennsylvania
city: McKeesport
country: United States
facility: UPMC McKeesport
state: Pennsylvania
city: Monroeville
country: United States
facility: UPMC East
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Arnold Palmer Medical Oncology-Mt Pleasant
state: Pennsylvania
city: New Castle
country: United States
facility: UPMC Jameson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC St. Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center St. Clair Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Shadyside
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Passavant
state: Pennsylvania
city: Seneca
country: United States
facility: UPMC Northwest (Franklin)
state: Pennsylvania
city: Seneca
country: United States
facility: UPMC Northwest (Oil City)
state: Pennsylvania
city: Washington
country: United States
facility: UPMC and the Washington Hospital Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology/Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine-Baylor Clinic
state: Texas
city: Houston
country: United States
facility: Harris County Hospital District-Ben Taub General Hospital
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Harris County Hospital District-Smith Clinic
state: Texas
city: Seattle
country: United States
facility: University of Washington Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Sara Tolaney, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.