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

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ClinicalTrials.gov Identifier: NCT01827163
Recruitment Status : Completed
First Posted : April 9, 2013
Results First Posted : December 18, 2019
Last Update Posted : December 18, 2019
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE April 2, 2013
First Posted Date  ICMJE April 9, 2013
Results First Submitted Date  ICMJE December 4, 2019
Results First Posted Date  ICMJE December 18, 2019
Last Update Posted Date December 18, 2019
Actual Study Start Date  ICMJE April 2013
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
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 [ Time Frame: 1 year ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 4, 2013)
feasibility [ Time Frame: 1 year ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2019)
Participants Toxicity Evaluated While on Study Treatment [ Time Frame: 1 year ]
All toxicities following chemotherapy will be graded using the National Cancer Institute - Common Toxicity Criteria version 4.0.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2013)
Safety [ Time Frame: 1 year ]
All toxicities following chemotherapy will be graded using the National Cancer Institute - Common Toxicity Criteria version 4.0.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Paclitaxel With Trastuzumab and Lapatinib in HER2-Positive Early Stage Breast Cancer
Official Title  ICMJE The Feasibility of Paclitaxel With Trastuzumab and Lapatinib in HER2-Positive Early Stage Breast Cancer
Brief Summary The purpose of this study is to study a new treatment for HER2-positive breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-Positive Early Stage Breast Cancer
Intervention  ICMJE
  • Drug: Paclitaxel
  • 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: Lapatinib
  • 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.
Study Arms  ICMJE 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.
Interventions:
  • Drug: Paclitaxel
  • Drug: Trastuzumab
  • Drug: Lapatinib
  • Drug: Pegfilgrastim
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 31, 2019)
20
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2013)
55
Actual Study Completion Date  ICMJE January 2019
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01827163
Other Study ID Numbers  ICMJE 13-002
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Principal Investigator: Chau Dang, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP