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Study of Lapatinib in Breast Cancer Patients With HER-2 Non-amplified Primary Tumors and HER-2 Positive or EGFR Positive Circulating Tumor Cells

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ClinicalTrials.gov Identifier: NCT00820924
Recruitment Status : Terminated
First Posted : January 12, 2009
Last Update Posted : March 28, 2012
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE January 8, 2009
First Posted Date  ICMJE January 12, 2009
Last Update Posted Date March 28, 2012
Study Start Date  ICMJE June 2008
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2011)
The efficacy of lapatinib in advanced breast cancer patients with HER-2 non-amplified primary tumours with HER-2 or EGFR positive circulating tumour cells. [ Time Frame: approx. 6 mos ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2009)
The efficacy of lapatinib in advanced breast cancer patients with HER-2 non-amplified primary tumours with HER-2 or EGFR positive circulating tumour cells.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2011)
  • Antitumour activity of lapatinib [ Time Frame: approx. 6 mos ]
  • Safety of lapatinib as measured by number of AEs [ Time Frame: approx. 6 mos ]
  • Early response of lapatinib on proliferation and the MAP kinase cascade by PET in a substudy in patients with EGFR positive CTCs only. [ Time Frame: approx. 6 mos ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2009)
  • To evaluate antitumour activitiy of lapatinib
  • To evaluate the safety of lapatinib
  • To determine the early response of lapatinib on proliferation and the MAP kinase cascade by PET in a substudy in patients with EGFR positive CTCs only.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Lapatinib in Breast Cancer Patients With HER-2 Non-amplified Primary Tumors and HER-2 Positive or EGFR Positive Circulating Tumor Cells
Official Title  ICMJE A Phase II Open Label, Multicenter Study to Evaluate the Efficacy and Safety of Daily Dose of Lapatinib in Advanced Breast Cancer Patients With HER-2 Non-amplified Primary Tumours and HER-2 Positive Circulating Tumour Cells or EGFR Positive Circulating Tumor Cells
Brief Summary

The underlying biology of the various patterns of metastasis observed in different tumour types remains unclear. The detection and characterization of circulating tumour cells in cancer patients has provided important new information about the progression of metastatic events. This information has important implications for cancer prognosis and therapy.

This multicenter open-label study is designed as a two-stage three-outcome phase II trial. The aim is to evaluate the efficacy and safety of daily dose of Lapatinib in advanced breast cancer patients with HER-2 non-amplified primary tumours and HER-2 or EGFR positive circulating tumour cells. Evaluation of HER-2 and EGFR status on circulating tumour cells will be performed by the means of the CellSearch equipment (Immunicon, Huntingdon Valley, PA, USA) and FISH method (PathVysion Kit -Abbott Laboratories).

Detailed Description

Rationale: Despite recent progress in gene-expression profiling studies, the underlying biology of the various patterns of metastasis observed in different tumour types remains unclear. The detection and characterization of circulating tumour cells in cancer patients has provided important new information about the progression of metastatic events. This information has important implications for cancer prognosis and therapy.

This open label, multicenter phase II study is designed to evaluate overall tumour response rate in advanced breast cancer patients with HER-2 non amplified primary tumours with positive HER-2 or EGFR circulating tumour cells treated with the dual tyrosine kinase inhibitor GW572016 (Lapatinib).

The patients will be allocated into one of the following two strata:

Stratum 1) Italian study group: Advanced breast cancer patients with HER-2 non-amplified primary tumours and HER-2 positive circulating tumour cells Stratum 2) UK study group: Advanced breast cancer patients with HER-2 non-amplified primary tumours and EGFR positive circulating tumour cells.

All of these patients will be treated with GW572016 (Lapatinib) which targets both HER-2 or EGFR receptors. A subgroup of patients enrolled into stratum 2 will be asked to participate in an additional sub-study using Positron Emission Tomography (PET) to quantify the potential early response to lapatinib treatment.

Study Design:

This study will be a multicenter open-label, phase II study to evaluate the efficacy and safety of daily dose of Lapatinib in advanced breast cancer patients with HER-2 non amplified primary tumours and positive HER-2 or EGFR circulating tumour cells.

Patients enrolled in this study will be treated with oral Lapatinib at the dose of 1,500 mg daily on day 1 to 28 every 4 weeks (q 4 weeks).

Patients will carefully be instructed on drug administration as far as Lapatinib oral intake is concerned. A daily dose of Lapatinib is six 250 mg tablets taken approximately at the same time each day. Lapatinib must be taken either at least 1 hour before or after meal.

Dose adjustment, modification and delays are permitted according to procedures described in the protocol. Initially 16 patients in each stratum will be treated; if 1 to 3 responses are observed, 15 additional patients will be treated, up to a total of 62 subjects with 31 subjects in each stratum.

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 Neoplasms, Breast
Intervention  ICMJE Drug: LAPATINIB
LAPATINIB 1500MG ORAL DOSE DAILY
Study Arms  ICMJE Experimental: LAPATINIB
LAPATINIB 1500MG ORAL ONCE DAILY
Intervention: Drug: LAPATINIB
Publications *

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: March 22, 2012)
23
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2009)
62
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female patients at least 18 years old with HER-2 negative breast cancer.
  • Patients must have evidence of HER-2 or EGFR positive circulating tumour cells in a peripheral blood sample taken at screening visit.
  • Patients must have measurable, metastatic disease and no brain metastasis requiring local therapy.
  • Other criteria include ECOG score 0 to 2, life expectancy > 12 weeks, baseline organ function at screening visit,
  • Previous treatment with anthracyclines and/or taxanes in the neo-adjuvant, adjuvant or advanced setting, and at least one line of treatment for metastatic disease.

Exclusion Criteria:

  • Unstable medical conditions, pregnant or lactating women.
  • Inability to provide informed consent.
  • Lack of physical integrity of the upper gastrointestinal (GI) tract.
  • Co-existing malignancy or malignancies within the last 5 years with the exception of basal cell carcinoma or in-situ carcinoma, concurrent anti-cancer therapies (chemo or hormonal therapy) or investigational drugs other than study drug.
  • Concurrent radiotherapy to the only target lesion or concurrent bisphosphonates if bone metastases are the only target lesions.
  • Previous treatment with anti HER-2 or anti-EGFR therapies.
  • Protocol specified treatment regimens that would be inappropriate for the management of the subject.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
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 Italy,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00820924
Other Study ID Numbers  ICMJE 105594
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date March 2012

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