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

NCT ID: NCT01827163

Last Updated: 2019-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2019-01-31

Brief Summary

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

Conditions

HER2-Positive Early Stage Breast Cancer

Keywords

Paclitaxel; Trastuzumab; Lapatinib; HER2; 13-002

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Trastuzumab

Intervention Type: DRUG

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.

Lapatinib

Intervention Type: DRUG

Pegfilgrastim

Intervention Type: DRUG

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.

Interventions

Paclitaxel

Intervention Type: 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.

Intervention Type: DRUG

Lapatinib

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

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

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chau Dang, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan-Kettering Cancer Commack

Commack, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26454612 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mskcc.org/

Memorial Sloan-Kettering Cancer Center

Other Identifiers

13-002

Identifier Type: -

Identifier Source: org_study_id