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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by The Methodist Hospital System
Sponsor:
Collaborators:
Celgene Corporation
GlaxoSmithKline
Information provided by (Responsible Party):
The Methodist Hospital System
ClinicalTrials.gov Identifier:
NCT02073487
First received: February 18, 2014
Last updated: February 25, 2014
Last verified: February 2014
  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.


Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab Emtansine
Drug: Trastuzumab
Drug: Lapatinib
Drug: Abraxane
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by The Methodist Hospital System:

Primary Outcome Measures:
  • pathological complete response rate (pCR) [ Time Frame: From date of randomization until the date of surgery, approximately 16 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Clinical Response Rate [ Time Frame: From date of randomization until completion of neoadjuvant treatment, approximately 16 weeks ] [ Designated as safety issue: No ]
    To determine the clinical response rate in patients with palpable disease.

  • breast imaging response to treatment [ Time Frame: approximately 16 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    To compare overall objective response rate in both treatment groups.

  • toxicity, safety and efficacy of study treatment [ Time Frame: approximately 16 weeks from randomization ] [ Designated as safety issue: Yes ]
    To assess toxicity, safety and efficacy of Trastuzumab Emtansine when combine with Lapatinib follow by Abraxane


Other Outcome Measures:
  • determine predictive markers [ Time Frame: approximately 1 year ] [ Designated as safety issue: No ]
    To determine predictive markers for sensitivity and resistance to Trastuzumab Emtansine when combined with Lapatinib follow by Abraxane


Estimated Enrollment: 30
Study Start Date: February 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TDM1 with Laptinib followed by Abraxane
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.
Drug: Trastuzumab Emtansine
trastuzumab emtansine [Kadcyla] Intravenous repeating dose every 3 weeks
Other Names:
  • TDM1
  • Kadcyla
Drug: Lapatinib
Lapatinib repeating dose taken orally every day for 6 weeks
Other Name: tykerb
Drug: Abraxane
Abraxane repeating dose weekly IV for up to 12 weeks
Active Comparator: Herceptin plus Lapatinib followed by paclitaxel
Trastuzumab (Herceptin) IV weekly plus Lapatinib oral daily for a total of six (6) weeks, followed by weekly IV paclitaxel for twelve (12) weeks.
Drug: Trastuzumab
Trastuzumab (Herceptin) Intravenous repeating dose weekly
Other Name: Herceptin
Drug: Lapatinib
Lapatinib repeating dose taken orally every day for 6 weeks
Other Name: tykerb
Drug: Paclitaxel
Paclitaxel IV repeating dose weekly for up to 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02073487

Contacts
Contact: Houston Methodist Cancer Center 713-441-0629 ccresearch@houstonmethodist.org

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Houston Methodist Cancer Center    713-441-0629    ccresearch@houstonmethodist.org   
Sub-Investigator: Angel A Rodriguez, MD         
Sub-Investigator: Daniel Lehane, MD         
Sub-Investigator: Tejal Patel, MD         
Sub-Investigator: Monisha Singh, MD         
Sub-Investigator: Jorge Darcourt, MD         
Sponsors and Collaborators
The Methodist Hospital System
Celgene Corporation
GlaxoSmithKline
Investigators
Principal Investigator: Jenny CN Chang, MD The Methodist Hospital System
  More Information

Additional Information:
No publications provided

Responsible Party: The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT02073487     History of Changes
Other Study ID Numbers: 1013-0164
Study First Received: February 18, 2014
Last Updated: February 25, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by 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
Trastuzumab
Lapatinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014