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

Overview[ - collapse ][ - ]

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.
ConditionBreast Cancer
InterventionDrug: Trastuzumab Emtansine
Drug: Trastuzumab
Drug: Lapatinib
Drug: Abraxane
Drug: Paclitaxel
PhasePhase 2
SponsorThe Methodist Hospital System
Responsible PartyThe Methodist Hospital System
ClinicalTrials.gov IdentifierNCT02073487
First ReceivedFebruary 18, 2014
Last UpdatedFebruary 25, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateFebruary 18, 2014
Last Updated DateFebruary 25, 2014
Start DateFebruary 2014
Estimated Primary Completion DateJune 2016
Current Primary Outcome Measurespathological 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.
Current 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

Descriptive Information[ + expand ][ + ]

Brief TitleNeoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab With Lapatinib and Paclitaxel
Official TitleRandomized 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)
Brief Summary
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 DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionBreast Cancer
InterventionDrug: Trastuzumab Emtansine
trastuzumab emtansine [Kadcyla] Intravenous repeating dose every 3 weeks
Other Names:
  • TDM1
  • Kadcyla
Drug: Trastuzumab
Trastuzumab (Herceptin) Intravenous repeating dose weekly
Other Names:
HerceptinDrug: Lapatinib
Lapatinib repeating dose taken orally every day for 6 weeks
Other Names:
tykerbDrug: Abraxane
Abraxane repeating dose weekly IV for up to 12 weeks
Drug: Paclitaxel
Paclitaxel IV repeating dose weekly for up to 12 weeks
Study Arm (s)
  • 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.
  • 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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment30
Estimated Completion DateJune 2016
Estimated Primary Completion DateJune 2015
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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Houston Methodist Cancer Center
713-441-0629
ccresearch@houstonmethodist.org
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT02073487
Other Study ID Numbers1013-0164
Has Data Monitoring CommitteeNo
Information Provided ByThe Methodist Hospital System
Study SponsorThe Methodist Hospital System
CollaboratorsCelgene Corporation
GlaxoSmithKline
Investigators Principal Investigator: Jenny CN Chang, MD Houston Methodist Hospital
Verification DateFebruary 2014

Locations[ + expand ][ + ]

Houston Methodist Hospital
Houston, Texas, United States, 77030
Contact: Houston Methodist Cancer Center | 713-441-0629 | ccresearch@houstonmethodist.org
Sub-Investigator: Angel A Rodriguez, MD
Recruiting