Paclitaxel With Trastuzumab and Lapatinib in HER2-Positive Early Stage Breast Cancer

The Feasibility of Paclitaxel With Trastuzumab and Lapatinib in HER2-Positive Early Stage Breast Cancer

The purpose of this study is to study a new treatment for HER2-positive breast cancer.

Study Overview

• Status: Completed
• Conditions: HER2-Positive Early Stage Breast Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Lapatinib; Drug: Trastuzumab; Drug: Pegfilgrastim

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan-Kettering Cancer Commack
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States
      • Memorial Sloan Kettering Rockville Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically confirmed adenocarcinoma with HER2/neu immunohistochemistry 3+ or FISH-amplified breast cancer with a ratio of ≥ 2.0
• Tumor size of ≤ 3 cm and node-negative disease. Nodes with single cells or tumor clusters < 0.2 mm by H&E or IHC are considered node-negative. Patients with micrometastasis (nodes with tumor clusters between 0.02 and 0.2 cm) are allowed. Further axillary dissection will be determined by the patient's surgeon as per standard of care.
• Patients must be ≥18 years of age.
• Patients must have an ECOG performance status of 0 or 1.
• Treatment should be started within 90 days of the final surgical procedure for breast cancer.
• Patients may have bilateral synchronous breast tumors. Patients may have received hormonal therapy for the purpose of chemoprevention but must be willing to discontinue prior to enrollment and while participating in this trial.
• If patients have peripheral neuropathy, it must be ≤ grade 1.
• Patients must be willing to discontinue sex hormonal therapy e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to enrollment. Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter.
• Hematologic parameters: absolute neutrophil count (ANC) ≥1500/μL and platelet count ≥100,000/μL.
• Non-hematologic parameters: total bilirubin must be ≤ 1.5 X institutional upper limit of normal (ULN), transaminases (SGOT or SGPT) ≤ 3.0 x ULN.
• Negative HCG pregnancy test for premenopausal women of reproductive capacity and for women less than 12 months after the menopause. LVEF by ECHO (with strain if possible) with LVEF of ≥ 50%. If an ECHO cannot be done, a MUGA may be performed.
• Patients must give written, informed consent indicating their understanding of and willingness to participate in the study.

Exclusion Criteria:

• Patients with stage IV breast cancer or undergoing chemotherapy, radiation therapy, immunotherapy, or biotherapy for current breast cancer.
• Pregnant or breastfeeding patients.
• Patients with a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers or in situ cervical cancer.
• Patients with unstable angina, congestive heart failure, or with a history of a myocardial infarction within 12 months. Patients with high-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV block, supraventricular arrhythmias which are not adequately rate-controlled). Patients are excluded if they have grade 3 QT prolongation (Appendix F) (>500 ms) or require drugs that may prolong the QT.
• Subjects who have current active hepatic (including hepatitis B or C) or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones).
• Patients with active, unresolved infections.
• Patients with a sensitivity to E. coli derived proteins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Paclitaxel With Trastuzumab and Lapatinib; Paclitaxel (T) at 175 mg/m2 q 2 weeks x 4 with filgrastim/pegfilgrastim + trastuzumab (H) + daily oral lapatinib (L), followed by trastuzumab q 3 weeks x 15 doses + daily oral lapatinib (HL). Pegfilgrastim 6mg will be given subcutaneously (SQ) on day # 2 of each paclitaxel administration. Filgrastim may be used in lieu of pegfilgrastim at physician's discretion. Trastuzumab will be administered weekly (4 mg/kg bolus followed by 2 mg/kg weekly) starting with paclitaxel treatment cycle # 1. After 4 cycles of paclitaxel, pts will receive trastuzumab on a q 3 weeks x 15 doses (to complete about one year). The q 3 week trastuzumab may be started from 1-3 weeks after the last dose of paclitaxel. A total of 15 infusions of trastuzumab will be given q 3 weeks after the completion of paclitaxel during the HL phase. Lapatinib will be given orally at 1000 mg daily, starting with paclitaxel during the THL phase & continued for the remaining year during the HL phase for about a year.

Drug: Paclitaxel; Drug: Lapatinib; Drug: Trastuzumab; The q 3 week trastuzumab may be started at the last dose of paclitaxel infusion or from 1-3 weeks after the last dose of paclitaxel. Trastuzumab may also be administered at a dose of 6mg/kg during the last dose of paclitaxel in the THL phase.; Drug: Pegfilgrastim; Pegfilgrastim SQ is given on day # 2 of each paclitaxel cycle and may be dropped at the last paclitaxel infusion. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Are Able to Complete THL (Paclitaxel, Trastuzumab, and Lapatinib) Without a Dose Delay or Reduction, Grade 3 or Greater QTc Prolongation	The primary objective of this trial is to determine the feasibility of this regimen in patients with node-negative HER-2/neu overexpressed /amplified breast cancer with a tumor size of < 3 cm. The regimen is considered feasible if patients are able to complete the paclitaxel, trastuzumab, and lapatinib (THL) portion of the regimen without a dose delay or reduction or grade 3 or greater QTc prolongation.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants Toxicity Evaluated While on Study Treatment	All toxicities following chemotherapy will be graded using the National Cancer Institute - Common Toxicity Criteria version 4.0.	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Chau Dang, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Iyengar NM, Fornier MN, Sugarman SM, Theodoulou M, Troso-Sandoval TA, D'Andrea GM, Drullinsky PR, Gajria D, Goldfarb SB, Comen EA, Lake DE, Modi S, Traina TA, Lacouture ME, Chen MF, Patil S, Baselga J, Norton L, Hudis CA, Dang CT. A Pilot Study of Dose-Dense Paclitaxel With Trastuzumab and Lapatinib for Node-negative HER2-Overexpressed Breast Cancer. Clin Breast Cancer. 2016 Apr;16(2):87-94. doi: 10.1016/j.clbc.2015.09.009. Epub 2015 Sep 25.

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2013
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: April 2, 2013
• First Submitted That Met QC Criteria: April 4, 2013
• First Posted (Estimate): April 9, 2013

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: HER2; Trastuzumab; Paclitaxel; Lapatinib; 13-002
• 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; Lapatinib
• Other Study ID Numbers: 13-002