Study of Preoperative Weekly Paclitaxel and Carboplatin With Lapatinib (Tykerb®) in Patients With ErbB2-Positive Stage I-III Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National University Hospital, Singapore
Sponsor:
Collaborator:
National Cancer Centre, Singapore
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01309607
First received: March 3, 2011
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of weekly paclitaxel and carboplatin, in combination with lapatinib, in the neoadjuvant treatment of non-metastatic erbB2-positive breast cancer.

Secondary objectives include:

  • To determine the safety and tolerability of weekly paclitaxel and carboplatin, combined with lapatinib, in an Asian population
  • To determine breast conservation rates following neoadjuvant paclitaxel/ carboplatin/ lapatinib
  • To determine clinical response rates and relapse-free survival of patients treated with neoadjuvant paclitaxel/ carboplatin/ lapatinib
  • To identify predictive tumour biomarkers for pathologic complete response

The investigators hypothesize that pathologic complete response rates will be improved from 15% to 35% with the neoadjuvant regimen of carboplatin/ paclitaxel/ lapatinib compared to standard chemotherapy alone in HER2 positive early stage breast cancers.


Condition Intervention Phase
ErbB2-Positive Stage I-III Breast Cancer
Drug: paclitaxel/carboplatin/lapatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Open-Label Study of Preoperative Weekly Paclitaxel and Carboplatin With Lapatinib (Tykerb®) in Patients With ErbB2-Positive Stage I-III Breast Cancer

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • Rate of pathologic complete response [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Treatment related toxicities [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Breast conservation rates [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Clinical response rates [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Relapse free survival (RFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Identification of tumor biomarkers that predict pathologic complete response [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 34
Study Start Date: April 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre-operative Therapy
Neoadjuvant paclitaxel/carboplatin/lapatinib x 12 weeks
Drug: paclitaxel/carboplatin/lapatinib

Drug doses for the neoadjuvant regimen:

  • Paclitaxel 80mg/m2, day 1, 8, 15 of a 21-day cycle
  • Carboplatin AUC of 2, day 1, 8 of a 21-day cycle
  • Lapatinib 750mg daily continuously

Detailed Description:
  • Pathologic complete response following neoadjuvant chemotherapy has been shown to be an independent, strong predictor of disease-free and overall survival in operable breast cancer
  • The addition of neoadjuvant trastuzumab to chemotherapy results in a 2-3 fold increase in pCR rates in operable ErbB2-positive breast cancer
  • Lapatinib is being explored as an alternative to trastuzumab in large clinical trials in operable ErbB2-positive breast cancer
  • In a randomised phase III adjuvant trial, BCIRG 006, non-anthracycline chemotherapy (docetaxel and carboplatin) has been shown to be as effective as conventional sequential anthracycline-containing chemotherapy and docetaxel, in combination with trastuzumab, but with improved cardiac safety
  • Weekly paclitaxel has been shown in a randomized phase III study to be the optimal adjuvant taxane regimen
  • Weekly paclitaxel and carboplatin, in combination with lapatinib, has demonstrated safety and efficacy in Phase I/II clinical studies of metastatic breast and ovarian cancer
  • The investigators aim to assess the efficacy of a non-anthracycline containing regimen, weekly paclitaxel and carboplatin, in combination with lapatinib in inducing pCR in the neoadjuvant treatment of ErbB2-positive non-metastatic breast cancer. The investigators hypothesize that this combination will achieve pCR rates of at least 35%
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • • Female, Age ≥ 18 years

    • Histologic or cytologic diagnosis of breast carcinoma
    • T1-4 breast cancer with measurable primary breast tumor, defined as palpable tumor with the largest diameter measuring 2.0cm or greater by calipers
    • Tumor is HER2 positive either by IHC (3+) or FISH amplification (amplification ratio >2.2)
    • Patients must not have received prior chemotherapy or hormonal therapy for the treatment of breast cancer
    • Karnofsky performance status of 70 or higher
    • Estimated life expectancy of at least 12 weeks
    • Adequate organ function including the following:

Bone marrow:

  • Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L
  • Platelets >= 100 x 109/L

Hepatic:

  • Bilirubin <= 1.5 x upper limit of normal (ULN),
  • ALT or AST <= 2.5x ULN

Renal:

o Calculated creatinine clearance >30ml/minute

  • Left ventricular ejection fraction >=50% measured by 2D echo or MUGA
  • Signed informed consent from patient or legal representative
  • Patient with reproductive potential must use an approved contraceptive method if appropriate (e.g. intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment

Exclusion Criteria:

  • • Prior treatment for locally advanced or metastatic breast cancer

    • Treatment within the last 30 days with any investigational drug
    • Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
    • Major surgery within 28 days of study drug administration
    • Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy
    • Breast feeding
    • Serious cardiac illness or medical conditions including but not confined to:

      • History of documented congestive cardiac failure or systolic dysfunction (LVEF <50%)
      • High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV block, supraventricular arrhythmias which are not adequately rate-controlled)
      • History of significant ischaemic heart disease
      • Clinically significant valvular heart disease
      • Poorly controlled hypertension (e.g. systolic BP > 180mmHg or diastolic >100mmHg)
    • Poorly controlled diabetes mellitus.
    • Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
    • History of significant neurological or mental disorder, including seizures or dementia.
    • Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment)
    • Concomitant use of CYP3A4 inhibitors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309607

Contacts
Contact: Soo Chin Lee +65 9620 8391 soo_chin_lee@nuhs.edu.sg
Contact: Christine C Vergara +65 6772 4619 christine_vergara@nuhs.edu.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119228
Principal Investigator: Soo Chin Lee         
Sponsors and Collaborators
National University Hospital, Singapore
National Cancer Centre, Singapore
Investigators
Principal Investigator: Soo Chin Lee National University Hospital, Singapore
  More Information

Publications:
Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01309607     History of Changes
Other Study ID Numbers: BR07/29/10
Study First Received: March 3, 2011
Last Updated: April 24, 2014
Health Authority: Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lapatinib
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014