- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02073487
Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel (TEAL)
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Houston Methodist Hospital
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Houston, Texas, United States, 77070
- Houston Methodist Hospital Willowbrook
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Sugar Land, Texas, United States, 77479
- Houston Methodist Hospital Sugar Land
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
antibody-drug conjugate of trastuzumab and emtansine
Other Names:
Dual tyrosine kinase inhibitor (HER2 and EGFR)
Other Names:
albumin-bound paclitaxel.
chemotherapy - microtubule inhibitor.
Other Names:
|
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.
|
anti-Her2 monoclonal antibody
Other Names:
anti-HER2 monoclonal antibody
Other Names:
chemotherapy - microtubule inhibitor
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathological Complete Response (pCR) RCB-0 or RCB-1
Time Frame: From date of randomization until the date of surgery, approximately 16 weeks
|
To evaluate the pathological complete response (pCR) in the breast after treatment with Trastuzumab Emtansine plus Lapatinib follow by Abraxane in women with HER2 Neu over-expressed breast cancer patients per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate. Residual cancer burden (RCB)-0 was synonymous with pCR, indicating no residual disease present. |
From date of randomization until the date of surgery, approximately 16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Breast Imaging Response to Treatment: Number of Eventual Responders in Standard Arm
Time Frame: From date of randomization until 6 weeks post treatment
|
To determine the change in tumor size by MRI at 6 weeks post treatment using RECIST v1.0.
Criteria.
Since all patients in the experimental arm achieved RCB-0 or RCB-1 (pCR), changes in tumor size by MRI were only evaluated in patients on the standard arm.
|
From date of randomization until 6 weeks post treatment
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
approximately 1 year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Jenny C Chang, MD, The Methodist Hospital Research Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Paclitaxel
- Trastuzumab
- Albumin-Bound Paclitaxel
- Ado-Trastuzumab Emtansine
- Lapatinib
- Pertuzumab
Other Study ID Numbers
- Pro00010074
- 1013-0164 (Other Identifier: HMRI IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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