Clinical Trials /

Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel

NCT02073487

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Neoadjuvant <span class="go-doc-concept go-doc-intervention">TDM1</span> With <span class="go-doc-concept go-doc-intervention">Lapatinib</span> and <span class="go-doc-concept go-doc-intervention">Abraxane</span> Compared With <span class="go-doc-concept go-doc-intervention">Trastuzumab</span> With <span class="go-doc-concept go-doc-intervention">Lapatinib</span> and <span class="go-doc-concept go-doc-intervention">Paclitaxel</span>

Title

  • Brief Title: Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab With Lapatinib and Paclitaxel
  • Official Title: Randomized Open Label Phase II Trial Of Neoadjuvant Trastuzumab Emtansine (Te) In Combination With Lapatinib (L) Follow by Abraxane (A) Compared With Trastuzumab Plus Lapatinib Follow by Paclitaxel In Her 2 Neu Over-Expressed Breast Cancer Patients (TEAL Trial)
  • Clinical Trial IDs

    NCT ID: NCT02073487

    ORG ID: 1013-0164

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Trastuzumab Emtansine TDM1, Kadcyla TDM1 with Laptinib followed by Abraxane
    Trastuzumab Herceptin Herceptin plus Lapatinib followed by paclitaxel
    Lapatinib tykerb TDM1 with Laptinib followed by Abraxane, Herceptin plus Lapatinib followed by paclitaxel
    Abraxane TDM1 with Laptinib followed by Abraxane
    Paclitaxel Herceptin plus Lapatinib followed by paclitaxel

    Trial Purpose

    Purpose: The purpose of this study is to evaluate the Pathological Complete Response (pCR)
    of the breast when trastuzumab emtansine (TDM-1) plus Lapatinib plus Abraxane is combined in
    newly diagnosed HER2 positive breast cancer.

    This is a randomized, open label Phase II neo-adjuvant study comparing the efficacy of
    neoadjuvant Trastuzumab Emtansine (TDM1) plus lapatinib follow by Abraxane, versus
    trastuzumab (herceptin) plus Lapatinib follow by paclitaxel.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    TDM1 with Laptinib followed by Abraxane Experimental Trastuzumab Emtansine IV every three weeks plus Lapatinib oral daily for a total of six (6) weeks followed by Abraxane IV weekly for twelve (12) weeks. Trastuzumab Emtansine, Lapatinib, Abraxane
    Herceptin plus Lapatinib followed by paclitaxel Active Comparator Trastuzumab (Herceptin) IV weekly plus Lapatinib oral daily for a total of six (6) weeks, followed by weekly IV paclitaxel for twelve (12) weeks. Trastuzumab, Lapatinib, Paclitaxel

    Eligibility Criteria

    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) 50% measured by
    echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan,

    - Negative serum or urine -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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    pathological complete response rate (pCR)

    Secondary Outcome Measures

    Clinical Response Rate

    breast imaging response to treatment

    objective response rate

    toxicity, safety and efficacy of study treatment

    Trial Keywords

    Neoadjuvant Breast Cancer

    HER2 positive Breast Cancer