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

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ClinicalTrials.gov Identifier: NCT02073487
Recruitment Status : Active, not recruiting
First Posted : February 27, 2014
Last Update Posted : July 25, 2018
Sponsor:
Collaborators:
Celgene Corporation
Novartis
The Methodist Hospital System
Information provided by (Responsible Party):
Jenny C. Chang, MD, The Methodist Hospital System

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: T-DM1 Drug: Trastuzumab Drug: Lapatinib Drug: Abraxane Drug: Paclitaxel Drug: Pertuzumab Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : February 2014
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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
antibody-drug conjugate of trastuzumab and emtansine
Other Names:
  • trastuzumab emtansine
  • Kadcyla

Drug: Lapatinib
Dual tyrosine kinase inhibitor (HER2 and EGFR)
Other Name: tykerb

Drug: Abraxane
albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.
Other Name: nab-paclitaxel

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
anti-Her2 monoclonal antibody
Other Name: Herceptin

Drug: Paclitaxel
chemotherapy - microtubule inhibitor
Other Name: Taxol

Drug: Pertuzumab
anti-HER2 monoclonal antibody
Other Name: Perjeta




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. objective response rate [ Time Frame: approximately 16 weeks ]
    To compare overall objective response rate in both treatment groups.

  4. 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


Other Outcome Measures:
  1. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02073487


Locations
United States, Texas
Houston Methodist Hospital
Houston, Texas, United States, 77030
Houston Methodist Hospital Willowbrook
Houston, Texas, United States, 77070
Houston Methodist Hospital Sugar Land
Sugar Land, Texas, United States, 77479
Sponsors and Collaborators
Jenny C. Chang, MD
Celgene Corporation
Novartis
The Methodist Hospital System
Investigators
Principal Investigator: Jenny C Chang, MD The Methodist Hospital System

Responsible Party: Jenny C. Chang, MD, Sponsor-Investigator/Principal Investigator, The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT02073487     History of Changes
Other Study ID Numbers: Pro00010074
1013-0164 ( Other Identifier: HMRI IRB )
First Posted: February 27, 2014    Key Record Dates
Last Update Posted: July 25, 2018
Last Verified: July 2018

Keywords provided by Jenny C. Chang, MD, The Methodist Hospital System:
Neoadjuvant Breast Cancer
HER2 positive Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Maytansine
Ado-trastuzumab emtansine
Lapatinib
Pertuzumab
Albumin-Bound Paclitaxel
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors