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

• Status: Completed
• Trial end date: 2019-01-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jenny C. Chang, MD; The Methodist Hospital Research Institute
• Collaborators: Celgene Corporation; Novartis; The Methodist Hospital System
• Treatments: Ado-Trastuzumab Emtansine; Albumin-Bound Paclitaxel; Lapatinib; Maytansine; Paclitaxel; Pertuzumab; Trastuzumab

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