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

NCT02073487 | Completed Phase 2 Results

• 2 other identifiers: Pro000100741013-0164
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

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.

Conditions

Breast Cancer

Keywords

Neoadjuvant Breast Cancer; HER2 positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) RCB-0 or RCB-1

  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 Outcomes (1)

• Breast Imaging Response to Treatment: Number of Eventual Responders in Standard Arm

  From date of randomization until 6 weeks post treatment

Other Outcomes (1)

• Determine Predictive Markers

  approximately 1 year

Study Arms (2)

T-DM1 + Lapatinib + Abraxane

EXPERIMENTAL

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; Drug: Lapatinib; Drug: Abraxane

Trastuzumab + Pertuzumab + Paclitaxel

ACTIVE COMPARATOR

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

Drug: Trastuzumab; Drug: Paclitaxel; Drug: Pertuzumab

Interventions

T-DM1 DRUG

antibody-drug conjugate of trastuzumab and emtansine

Also known as: trastuzumab emtansine, Kadcyla

T-DM1 + Lapatinib + Abraxane

Trastuzumab DRUG

anti-Her2 monoclonal antibody

Also known as: Herceptin

Trastuzumab + Pertuzumab + Paclitaxel

Lapatinib DRUG

Dual tyrosine kinase inhibitor (HER2 and EGFR)

Also known as: tykerb

T-DM1 + Lapatinib + Abraxane

Abraxane DRUG

albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.

Also known as: nab-paclitaxel

T-DM1 + Lapatinib + Abraxane

Paclitaxel DRUG

chemotherapy - microtubule inhibitor

Also known as: Taxol

Trastuzumab + Pertuzumab + Paclitaxel

Pertuzumab DRUG

anti-HER2 monoclonal antibody

Also known as: Perjeta

Trastuzumab + Pertuzumab + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead
• Celgene Corporation: collaborator
• Novartis: collaborator

Study Sites (3)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital Willowbrook

Houston, Texas, 77070, United States

Location

Houston Methodist Hospital Sugar Land

Sugar Land, Texas, 77479, United States

Location

Related Publications (1)

• 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.

  PMID: 31477168 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; Trastuzumab; Lapatinib; Albumin-Bound Paclitaxel; 130-nm albumin-bound paclitaxel; Paclitaxel; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins

Results Point of Contact

• Title: Jenny Chang
• Organization: Houston Methodist

jcchang@houstonmethodist.org

713-441-0681

Study Officials

• Jenny C Chang, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 18, 2014
• First Posted: February 27, 2014
• Study Start: February 1, 2014
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: September 22, 2021
• Results First Posted: September 22, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)