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

NCT ID: NCT02073487

Last Updated: 2021-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2019-01-31

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.

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

T-DM1

Intervention Type: DRUG

antibody-drug conjugate of trastuzumab and emtansine

Lapatinib

Intervention Type: DRUG

Dual tyrosine kinase inhibitor (HER2 and EGFR)

Abraxane

Intervention Type: DRUG

albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.

Trastuzumab + Pertuzumab + Paclitaxel

Trastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks.

Group Type: ACTIVE_COMPARATOR

Pertuzumab

Intervention Type: DRUG

anti-HER2 monoclonal antibody

Trastuzumab

Intervention Type: DRUG

anti-Her2 monoclonal antibody

Paclitaxel

Intervention Type: DRUG

chemotherapy - microtubule inhibitor

Interventions

Pertuzumab

anti-HER2 monoclonal antibody

Intervention Type: DRUG

T-DM1

antibody-drug conjugate of trastuzumab and emtansine

Intervention Type: DRUG

Trastuzumab

anti-Her2 monoclonal antibody

Intervention Type: DRUG

Lapatinib

Dual tyrosine kinase inhibitor (HER2 and EGFR)

Intervention Type: DRUG

Abraxane

albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.

Intervention Type: DRUG

Paclitaxel

chemotherapy - microtubule inhibitor

Intervention Type: DRUG

Other Intervention Names

trastuzumab emtansine; Kadcyla; Herceptin; tykerb; nab-paclitaxel; Taxol; Perjeta

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Jenny C. Chang, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jenny C Chang, MD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Locations

Houston Methodist Hospital

Houston, Texas, United States

Houston Methodist Hospital Willowbrook

Houston, Texas, United States

Houston Methodist Hospital Sugar Land

Sugar Land, Texas, United States

Countries

United States

References

Patel TA, Ensor JE, Creamer SL, Boone T, Rodriguez AA, Niravath PA, Darcourt JG, Meisel JL, Li X, Zhao J, Kuhn JG, Rosato RR, Qian W, Belcheva A, Schwartz MR, Kaklamani VG, Chang JC. A randomized, controlled phase II trial of neoadjuvant ado-trastuzumab emtansine, lapatinib, and nab-paclitaxel versus trastuzumab, pertuzumab, and paclitaxel in HER2-positive breast cancer (TEAL study). Breast Cancer Res. 2019 Sep 2;21(1):100. doi: 10.1186/s13058-019-1186-0.

Reference Type: DERIVED

PMID: 31477168 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1013-0164

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00010074

Identifier Type: -

Identifier Source: org_study_id