ATEMPT 2.0: Adjuvant T-DM1 vs TH

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT04893109
Collaborator
Genentech, Inc. (Industry)
500
17
2
82.5
29.4
0.4

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a randomized phase II adjuvant study for women and men with Stage I HER2-positive invasive breast cancer. Participants will be randomized into one of two treatment arms in this study and receive:

  • Arm 1: trastuzumab-emtansine (T-DM1, Kadcyla) and trastuzumab SC (Herceptin Hylecta)

  • Arm 2: paclitaxel and trastuzumab SC (Herceptin Hylecta) This research study is looking to see if the study drug T-DM1 followed by trastuzumab SC will have less side-effects than traditional HER2-positive breast cancer treatment of trastuzumab and paclitaxel.The study is also looking to learn about the long-term benefits and disease-free survival of participants who are treated with T-DM1 followed by trastuzumab SC.

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. More specifically, the trastuzumab in T-DM1 first binds to the HER2 protein on the surface of the breast cancer cells and the DM1 then enters the cells and can cause them to die, preventing tumor growth. The FDA (the U.S. Food and Drug Administration) has not approved T-DM1 for use on its own in patients with stage I, II, or III breast cancer. However, it has been approved for use in (a) advanced or metastatic, previously treated breast cancer and (b) in some patients receiving postoperative treatment after preoperative chemotherapy and surgery have been completed.

Trastuzumab SC is a subcutaneous form of trastuzumab.Trastuzumab is a monoclonal antibody, which are disease-fighting proteins made by cloned immune cells. Paclitaxel and trastuzumab are considered a standard-of-care regimen in early breast cancer. Trastuzumab is FDA-approved to be administered as an IV (intravenous) or subcutaneous (muscular injection).

The research study procedures include screening for eligibility and study treatment including laboratory evaluations and follow up visits.

Participants will receive study treatment for a year in total and will be followed for 5 years after treatment.

It is expected that about 500 people will take part in this research study.

Genentech is supporting this research study by providing funding for the study and supplying trastuzumab-emtansine (T-DM1) and trastuzumab SC (subcutaneous).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
500 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
participants are randomized in a 2-1 fashion to Arm A vs. Arm Bparticipants are randomized in a 2-1 fashion to Arm A vs. Arm B
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Jun 16, 2021
Anticipated Primary Completion Date :
May 1, 2025
Anticipated Study Completion Date :
May 1, 2028

Arms and Interventions

Arm Intervention/Treatment
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

Drug: trastuzumab-emtansine
intravenous infusion
Other Names:
  • T-DM1
  • Kadcyla
  • Drug: Trastuzumab SC
    Muscular injection
    Other Names:
  • Herceptin Hylecta
  • 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.

    Drug: Trastuzumab SC
    Muscular injection
    Other Names:
  • Herceptin Hylecta
  • Drug: Paclitaxel
    intravenous infusion
    Other Names:
  • Taxol
  • Onxal
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of clinically relevant toxicities (CRT) [First 18 weeks of treatment]

      Compare the incidence of clinically relevant toxicities (CRT) in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine followed by trastuzumab SC to the incidence in those treated with paclitaxel in combination with trastuzumab SC as assessed by PRO-CTCAE

    2. Disease Free Survival (DFS) [Time from randomization to first Disease Free Survival (DFS) event up to 72 months]

      Evaluate disease-free survival in the T-DM1 followed by trastuzumab SC arm

    Secondary Outcome Measures

    1. Grade 3 and 4 adverse events [Enrollment to end of treatment up to 1 year]

      Compare the incidence of all grade 3 and 4 adverse events in patients treated with adjuvant trastuzumab emtansine followed by trastuzumab SC to the incidence in those receiving paclitaxel in combination with trastuzumab SC

    2. Quality of Life Assessment: FACT B [Enrollment to end of treatment up to 1 year]

      Compare responses to FACT-B quality of life (QOL) questionnaire in patients receiving trastuzumab emtansine followed by trastuzumab SC to that experienced by patients receiving paclitaxel in combination with trastuzumab SC.

    3. Symptoms related to therapy [Enrollment to end of treatment up to 1 year]

      Evaluate symptoms related to therapy in patients receiving trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel in combination with trastuzumab SC using the Rotterdam Symptom Checklist (RSCL)

    4. Symptoms related to therapy [Enrollment to end of treatment up to 1 year]

      Evaluate symptoms related to therapy in patients receiving trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel in combination with trastuzumab SC using the Patient Neurotoxicity Questionnaire (PNQ)

    5. Effects of therapy on work productivity [Enrollment to end of treatment up to 1 year]

      Evaluate effects of therapy on work productivity and activity using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP) in patients receiving trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel in combination with trastuzumab SC

    6. Effect of alopecia on patients [Enrollment to end of treatment up to 1 year]

      Evaluate the effects of alopecia on patients receiving paclitaxel in combination with trastuzumab SC using an alopecia questionnaire

    7. Incidence of Side Effects [Enrollment to end of treatment up to 1 year]

      Compare incidence of sensory neuropathy, headache, arthralgia and myalgia using PRO-CTCAE criteria in patients receiving trastuzumab emtansine followed by trastuzumab SC to that experienced by patients receiving paclitaxel in combination with trastuzumab SC

    8. Incidence of grade 3-4 cardiac left ventricular dysfunction [Enrollment to end of treatment up to 1 year]

      Evaluate the incidence of grade 3-4 cardiac left ventricular dysfunction in patients treated with adjuvant trastuzumab emtansine followed by trastuzumab SC compared to those receiving paclitaxel with trastuzumab SC

    9. Incidence of trastuzumab-emtansine-induced grade 2-4 thrombocytopenia [Enrollment to end of treatment up to 1 year]

      Evaluate the incidence of trastuzumab-emtansine-induced grade 2-4 thrombocytopenia

    10. Percentage of patients with amenorrhea [Enrollment to end of treatment up to 1 year]

      Investigate the percentage of patients with amenorrhea at various time points after the start of treatment in premenopausal women receiving treatment with trastuzumab emtansine followed by trastuzumab SC and paclitaxel with trastuzumab SC

    11. Evaluation of gene predictors of trastuzumab-emtansine-induced grade 2-4 [Enrollment to end of treatment up to 1 year]

      Evaluate gene biomarkers predictive of trastuzumab-emtansine-induced grade 2-4 thrombocytopenia

    12. Gene Profiling [Enrollment to end of treatment up to 1 year]

      Utilize genomic profiling to query a large panel of cancer gene mutations and gene expression in patients with Stage I HER2-positive breast cancer

    13. Radiation therapy Toxicity [Enrollment to end of treatment up to 1 year]

      Evaluate the incidence of toxicities attributed to radiation therapy when given concurrently with trastuzumab SC after receipt of either trastuzumab emtansine or paclitaxel

    14. Overall survival [Enrollment to end of treatment up to 1 year]

      Describe overall survival in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine followed by trastuzumab SC

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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: defined as 3+ by immunohistochemistry. FISH results will not be considered for eligibility.

    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. 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 ≤ 7 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stamford Hospital Stamford Connecticut United States 06904
    2 Eastern Maine Medical Center (Northern Light) Brewer Maine United States 04412
    3 New England Cancer Specialists Scarborough Maine United States 04074
    4 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    5 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    6 Massachusetts General Hospital Boston Massachusetts United States 02215
    7 Dana-Farber at St. Elizabeth's Medical Center Brighton Massachusetts United States 02135
    8 Mass General North Shore Cancer Center Danvers Massachusetts United States 01923
    9 Dana-Farber Cancer Instiute - Merrimack Valley Methuen Massachusetts United States 01844
    10 Dana-Farber at Milford Milford Massachusetts United States 01757
    11 Newton Wellesley Hospital Newton Massachusetts United States 02462
    12 Berkshire Medical Center Pittsfield Massachusetts United States 01201
    13 Dana Farber at South Shore Hospital Weymouth Massachusetts United States 02190
    14 Dana-Farber Cancer Insitute at Londonderry Hospital Londonderry New Hampshire United States 03053
    15 New York University Langone Hospital - Long Island Mineola New York United States 11501
    16 New York University Langone Health New York New York United States 10016
    17 Sarah Cannon Research Institute Nashville Tennessee United States 37203

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • Genentech, Inc.

    Investigators

    • Principal Investigator: Sara Tolaney, MD, PhD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sara Tolaney, Principal Investigator, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT04893109
    Other Study ID Numbers:
    • 21-159
    First Posted:
    May 19, 2021
    Last Update Posted:
    Jun 22, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Sara Tolaney, Principal Investigator, Dana-Farber Cancer Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 22, 2022