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Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel (TEAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02073487
Recruitment Status : Completed
First Posted : February 27, 2014
Last Update Posted : April 16, 2019
Celgene Corporation
The Methodist Hospital System
Information provided by (Responsible Party):
Jenny C. Chang, MD, The Methodist Hospital System

Tracking Information
First Submitted Date  ICMJE February 18, 2014
First Posted Date  ICMJE February 27, 2014
Last Update Posted Date April 16, 2019
Study Start Date  ICMJE February 2014
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2014)
pathological complete response rate (pCR) [ Time Frame: From date of randomization until the date of surgery, approximately 16 weeks ]
To evaluate the pathological complete response rate (pCR) in the breast after treatment with Trastuzumab Emtansine plus Lapatinib follow by Abraxane in women with HER2 Neu over-expressed breast cancer patients.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02073487 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2014)
  • Clinical Response Rate [ Time Frame: From date of randomization until completion of neoadjuvant treatment, approximately 16 weeks ]
    To determine the clinical response rate in patients with palpable disease.
  • breast imaging response to treatment [ Time Frame: approximately 16 weeks ]
    To determine the imaging response to neoadjuvant therapy through breast imaging (mammogram, ultrasound and MRI) using RECIST.
  • objective response rate [ Time Frame: approximately 16 weeks ]
    To compare overall objective response rate in both treatment groups.
  • toxicity, safety and efficacy of study treatment [ Time Frame: approximately 16 weeks from randomization ]
    To assess toxicity, safety and efficacy of Trastuzumab Emtansine when combine with Lapatinib follow by Abraxane
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 25, 2014)
determine predictive markers [ Time Frame: approximately 1 year ]
To determine predictive markers for sensitivity and resistance to Trastuzumab Emtansine when combined with Lapatinib follow by Abraxane
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel
Official Title  ICMJE Randomized Open Label PhII Trial of Neoadjuvant Trastuzumab Emtansine (Te) in Combination w/Lapatinib (L) Followed by Abraxane (A) Compared w/Trastuzumab Plus Pertuzumab Followed by Paclitaxel in Her2/Neu Over-Expressed Breast Cancer Patients
Brief Summary This is a randomized, open label Phase II neoadjuvant study comparing the efficacy and safety of trastuzumab emtansine (T-DM1) plus lapatinib (L)followed by abraxane (A) versus trastuzumab plus pertuzumab followed by paclitaxel in patients with HER2-overexpressing breast cancer.
Detailed Description This is a randomized, open label Phase II neoadjuvant study comparing the efficacy and safety of trastuzumab emtansine (T-DM1) plus lapatinib (L) followed by abraxane (A) versus trastuzumab plus pertuzumab followed by paclitaxel in patients with HER2-overexpressing breast cancer. Patients will be randomized (1:1) to one of the two treatment arms: arm 1, trastuzumab emtansine plus lapatinib for 6 weeks, followed by trastuzumab emtansine plus lapatinib plus abraxane for 12 weeks; arm 2, trastuzumab plus pertuzumab for six weeks, followed by trastuzumab plus pertuzumab plus paclitaxel for 12 weeks. Patients will undergo surgery after neoadjuvant therapy. All patients will have a core needle biopsy at baseline, after week 6, and at the time of disease progression. Surgical specimens will be obtained after week 18.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: T-DM1
    antibody-drug conjugate of trastuzumab and emtansine
    Other Names:
    • trastuzumab emtansine
    • Kadcyla
  • Drug: Trastuzumab
    anti-Her2 monoclonal antibody
    Other Name: Herceptin
  • Drug: Lapatinib
    Dual tyrosine kinase inhibitor (HER2 and EGFR)
    Other Name: tykerb
  • Drug: Abraxane
    albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.
    Other Name: nab-paclitaxel
  • Drug: Paclitaxel
    chemotherapy - microtubule inhibitor
    Other Name: Taxol
  • Drug: Pertuzumab
    anti-HER2 monoclonal antibody
    Other Name: Perjeta
Study Arms  ICMJE
  • Experimental: T-DM1 + Lapatinib + Abraxane
    T-DM1 intravenously (IV) every three weeks plus L orally once daily for 6 weeks followed by abraxane IV weekly for 12 weeks.
    • Drug: T-DM1
    • Drug: Lapatinib
    • Drug: Abraxane
  • Active Comparator: Trastuzumab + Pertuzumab + Paclitaxel
    Trastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks.
    • Drug: Trastuzumab
    • Drug: Paclitaxel
    • Drug: Pertuzumab
Publications * Patel TA, Ensor JE, Creamer SL, Boone T, Rodriguez AA, Niravath PA, Darcourt JG, Meisel JL, Li X, Zhao J, Kuhn JG, Rosato RR, Qian W, Belcheva A, Schwartz MR, Kaklamani VG, Chang JC. A randomized, controlled phase II trial of neoadjuvant ado-trastuzumab emtansine, lapatinib, and nab-paclitaxel versus trastuzumab, pertuzumab, and paclitaxel in HER2-positive breast cancer (TEAL study). Breast Cancer Res. 2019 Sep 2;21(1):100. doi: 10.1186/s13058-019-1186-0.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 23, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: February 25, 2014)
Actual Study Completion Date  ICMJE January 2019
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female gender;
  • Age ≥18 years;
  • Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
  • Histologically confirmed invasive breast cancer:
  • Primary tumor greater than 1 cm diameter, measured by clinical examination and mammography or ultrasound.
  • Any N,
  • No evidence of metastasis (M0) (isolated supra-clavicular node involvement allowed);
  • Over expression and/or amplification of HER2 in the invasive component of the primary tumor and confirmed by a certified laboratory prior to randomization.
  • Known hormone receptor status.
  • Hematopoietic status:
  • CBC not less than .75 of institutional lower limit. Absolute neutrophil count ≥ 1,5 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Hemoglobin at least 9 g/dl,
  • Hepatic status:

Serum total bilirubin ≤ 2 x upper limit of normal (ULN). In the case of known Gilbert's syndrome, a higher serum total bilirubin (< 1.5 x ULN) is allowed, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3.5 times ULN, Alkaline phosphatase ≤ 2.5 times ULN, • Renal status: Creatinine ≤ 1.5mg/dL,

• Cardiovascular: Baseline left ventricular ejection fraction (LVEF) ³ ≥50% measured by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan,

  • Negative serum or urine β-hCG pregnancy test at screening for patients of childbearing potential within 2-weeks (preferably 7 days) prior to randomization.
  • Fertile patients must use effective contraception (barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed)
  • Signed informed consent form (ICF)
  • Patient accepts to make available tumor samples for submission to central laboratory to conduct translational studies as part of this protocol.

Exclusion Criteria:

  • Previous (less than 5 years) or current history of malignant neoplasms, except for curatively treated: Basal and squamous cell carcinoma of the skin; Carcinoma in situ of the cervix.
  • Patients with a prior malignancy diagnosed more than 5 years prior to randomization may enter the study.
  • Preexisting peripheral neuropathy ≥ grade 2
  • Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic therapy with oxygen;
  • Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety;
  • Unresolved or unstable, serious adverse events from prior administration of another investigational drug;
  • Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of ICF;
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
  • Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy other than the trial therapies);
  • Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab Emtansine, trastuzumab, lapatinib, paclitaxel, abraxane or their components;
  • Pregnant or lactating women;
  • Concomitant use of CYP3A4 inhibitors or inducers
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients have an active infection and require IV or oral antibiotics.
  • Pregnant or breast-feeding women
  • Patients unwilling or unable to comply with the protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02073487
Other Study ID Numbers  ICMJE Pro00010074
1013-0164 ( Other Identifier: HMRI IRB )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jenny C. Chang, MD, The Methodist Hospital System
Study Sponsor  ICMJE Jenny C. Chang, MD
Collaborators  ICMJE
  • Celgene Corporation
  • Novartis
  • The Methodist Hospital System
Investigators  ICMJE
Principal Investigator: Jenny C Chang, MD The Methodist Hospital System
PRS Account The Methodist Hospital System
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP