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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

Primary Purpose

Neoplasms, Breast

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LAPATINIB
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasms, Breast focused on measuring HER-2, Circulating Tumour Cell (CTC), EGFR, Lapatinib (GW572016), Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LAPATINIB

Arm Description

LAPATINIB 1500MG ORAL ONCE DAILY

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Antitumour activity of lapatinib
Safety of lapatinib as measured by number of AEs
Early response of lapatinib on proliferation and the MAP kinase cascade by PET in a substudy in patients with EGFR positive CTCs only.

Full Information

First Posted
January 8, 2009
Last Updated
March 22, 2012
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00820924
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Terminated
Study Start Date
June 2008 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Breast
Keywords
HER-2, Circulating Tumour Cell (CTC), EGFR, Lapatinib (GW572016), Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LAPATINIB
Arm Type
Experimental
Arm Description
LAPATINIB 1500MG ORAL ONCE DAILY
Intervention Type
Drug
Intervention Name(s)
LAPATINIB
Intervention Description
LAPATINIB 1500MG ORAL DOSE DAILY
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Antitumour activity of lapatinib
Time Frame
approx. 6 mos
Title
Safety of lapatinib as measured by number of AEs
Time Frame
approx. 6 mos
Title
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Rimini
State/Province
Emilia-Romagna
ZIP/Postal Code
47900
Country
Italy
Facility Name
GSK Investigational Site
City
Udine
State/Province
Friuli-Venezia-Giulia
ZIP/Postal Code
33100
Country
Italy
Facility Name
GSK Investigational Site
City
Bergamo
State/Province
Lombardia
ZIP/Postal Code
24128
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20121
Country
Italy
Facility Name
GSK Investigational Site
City
Rozzano (MI)
State/Province
Lombardia
ZIP/Postal Code
20089
Country
Italy
Facility Name
GSK Investigational Site
City
Livorno
State/Province
Toscana
ZIP/Postal Code
57124
Country
Italy
Facility Name
GSK Investigational Site
City
Prato (PO)
State/Province
Toscana
ZIP/Postal Code
59100
Country
Italy
Facility Name
GSK Investigational Site
City
Perugia
State/Province
Umbria
ZIP/Postal Code
06156
Country
Italy
Facility Name
GSK Investigational Site
City
Ancona
ZIP/Postal Code
60020
Country
Italy
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23667487
Citation
Stebbing J, Payne R, Reise J, Frampton AE, Avery M, Woodley L, Di Leo A, Pestrin M, Krell J, Coombes RC. The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study. PLoS One. 2013 May 7;8(5):e62543. doi: 10.1371/journal.pone.0062543. Print 2013.
Results Reference
derived
PubMed Identifier
22476856
Citation
Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C, Gori S, Coombes CR, Stebbing J, Biganzoli L, Buyse M, Di Leo A. Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study. Breast Cancer Res Treat. 2012 Jul;134(1):283-9. doi: 10.1007/s10549-012-2045-1. Epub 2012 Apr 4.
Results Reference
derived

Learn more about this trial

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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