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

Title

  • Brief Title: Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: Pro00010074
  • SECONDARY ID: 1013-0164
  • NCT ID: NCT02073487

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
T-DM1trastuzumab emtansine, KadcylaT-DM1 + Lapatinib + Abraxane
TrastuzumabHerceptinTrastuzumab + Pertuzumab + Paclitaxel
LapatinibtykerbT-DM1 + Lapatinib + Abraxane
Abraxanenab-paclitaxelT-DM1 + Lapatinib + Abraxane
PaclitaxelTaxolTrastuzumab + Pertuzumab + Paclitaxel
PertuzumabPerjetaTrastuzumab + Pertuzumab + Paclitaxel

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
T-DM1 + Lapatinib + AbraxaneExperimentalT-DM1 intravenously (IV) every three weeks plus L orally once daily for 6 weeks followed by abraxane IV weekly for 12 weeks.
  • T-DM1
  • Lapatinib
  • Abraxane
Trastuzumab + Pertuzumab + PaclitaxelActive ComparatorTrastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks.
  • Trastuzumab
  • Paclitaxel
  • Pertuzumab

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) 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:pathological complete response rate (pCR)
Time Frame:From date of randomization until the date of surgery, approximately 16 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Clinical Response Rate
Time Frame:From date of randomization until completion of neoadjuvant treatment, approximately 16 weeks
Safety Issue:
Description:To determine the clinical response rate in patients with palpable disease.
Measure:breast imaging response to treatment
Time Frame:approximately 16 weeks
Safety Issue:
Description:To determine the imaging response to neoadjuvant therapy through breast imaging (mammogram, ultrasound and MRI) using RECIST.
Measure:objective response rate
Time Frame:approximately 16 weeks
Safety Issue:
Description:To compare overall objective response rate in both treatment groups.
Measure:toxicity, safety and efficacy of study treatment
Time Frame:approximately 16 weeks from randomization
Safety Issue:
Description:To assess toxicity, safety and efficacy of Trastuzumab Emtansine when combine with Lapatinib follow by Abraxane

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Jenny C. Chang, MD

Trial Keywords

  • Neoadjuvant Breast Cancer
  • HER2 positive Breast Cancer

Last Updated

April 16, 2019