Neoplasms, BreastPhase 2NCT00820924
Study of Lapatinib in Breast Cancer Patients With HER-2 Non-amplified Primary Tumors and HER-2 Positive or EGFR Positive Circulating Tumor Cells
A Phase 2 study testing LAPATINIB in people with Neoplasms, Breast, run by GlaxoSmithKline at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- LAPATINIB
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Jun 2008to Jul 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
Italy9 sites
GSK Investigational Site
Ancona, 60020
GSK Investigational Site
Bergamo, Lombardy, 24128
GSK Investigational Site
Livorno, Tuscany, 57124
GSK Investigational Site
Milan, Lombardy, 20121
GSK Investigational Site
Perugia, Umbria, 06156
GSK Investigational Site
Prato (PO), Tuscany, 59100
GSK Investigational Site
Rimini, Emilia-Romagna, 47900
GSK Investigational Site
Rozzano (MI), Lombardy, 20089
GSK Investigational Site
Udine, Friuli Venezia Giulia, 33100
About this study
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
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).
Read the 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.
- Conditions
- Neoplasms, Breast
- Being tested
- LAPATINIB
- Keywords
- HER-2, Circulating Tumour Cell (CTC), EGFR, Lapatinib (GW572016), Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAPATINIBDrug
LAPATINIB 1500MG ORAL DOSE DAILY
| Study group | Role | What they receive |
|---|---|---|
| LAPATINIB | Experimental | LAPATINIB 1500MG ORAL ONCE DAILY Receives: Drug: LAPATINIB |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: approx. 6 mos
Secondary outcomes (3)
Antitumour activity of lapatinib
Measured: approx. 6 mos
Safety of lapatinib as measured by number of AEs
Measured: 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.
Measured: approx. 6 mos
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2009 (estimated)
- Study startJun 2008
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00820924
- Sponsor's protocol ID
- 105594
- Status last verified
- Mar 2012
- First submitted
- 8 Jan 2009
- Last updated
- 28 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23667487Pestrin 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.
PubMed 22476856
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00820924
- Acronym / sponsor ID
- 105594
- Conditions
- Neoplasms, Breast
- Keywords
- HER-2, Circulating Tumour Cell (CTC), EGFR, Lapatinib (GW572016), Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 23 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 12 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LAPATINIB | Experimental | Drug: LAPATINIBLAPATINIB 1500MG ORAL ONCE DAILY |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LAPATINIBLAPATINIB 1500MG ORAL DOSE DAILY | Drug | LAPATINIB |
Primary outcome
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
3 secondary outcomes
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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2012.
- Derived from this study: PubMed 23667487Stebbing 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.
- Derived from this study: PubMed 22476856Pestrin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LAPATINIB in people with Neoplasms, Breast, run by GlaxoSmithKline at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00820924, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2012.