Metastatic Breast CancerPhase 2NCT00225758
Lapatinib in Metastatic Breast Cancer Resistant to Hormone Therapy
A Phase 2 study testing Lapatinib in people with Metastatic Breast Cancer, run by Gary Schwartz at 3 sites in United States.
Trial summary
Two thirds or more of breast cancers are dependent on estrogen for growth. We use a number of estrogen-blocking medicines for treatment of metastatic breast cancer. The treatment response to these agents is unpredictable, however, and approximately one-third of patients with metastatic breast cancer with receptors for… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Lapatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2006to Oct 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with histologically or cytologically proven metastatic breast cancer.
- Patients with either estrogen or progesterone receptor positivity on the most recently examined tumor biopsy.
- Patients must have most recently been using an anti-estrogen (tamoxifen, toremifene, raloxifene, or fulvestrant) or an aromatase inhibitor.
- Patients must have had either a partial response or better, or stable disease for 24 weeks or longer, followed by disease progression, on the current or most recent hormonal therapy for management of metastatic breast cancer.
- Patients must be enrolled within six weeks of defining disease progression on hormonal therapy.
- Patients must have stopped fulvestrant at least four weeks prior and other endocrine therapy at least two weeks prior to enrollment on study.
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- Patients must have either measurable disease or at least one evaluable bone lesion that has not been irradiated. Measurable disease is not necessary.
- Estimated life expectancy of at least 6 months.
- ECOG performance status 0-2.
- Adequate hematologic, hepatic, and renal function.
- Patients must be post-menopausal, or they must be practicing either abstinence or an adequate method of contraception, or their sexual partner must be sterile.
- All patients must be able to swallow, retain, and absorb oral medications.
- All patients must be able to give informed consent indicating that they are aware of the investigational nature of this study.
Who cannot join
- Patients may not have received an investigational agent within the prior four weeks.
- Patients may not have received trastuzumab within three weeks of study entry.
- Patients may not have had major surgery within the prior two weeks.
- Patients may not have Class III or IV heart failure as defined by the NYHA functional classification system.
- Patients may not have a left ventricular ejection fraction < 40% based on MUGA or echocardiogram.
- Patients may not have uncontrolled brain metastases or leptomeningeal disease.
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- Patients may not have rapidly progressive visceral metastases.
- Patients may not have a serious illness or conditions including clinically significant cardiac disease, angina pectoris, serious psychiatric disorder, or an active infection.
- Patients may not be receiving concurrent medications (listed in the protocol) which may interact with lapatinib during treatment with lapatinib.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
North Shore University Hospital
Lake Success, New York, 11042
Norris Cotton Cancer Center
Lebanon, New Hampshire, 03756
About this study
Official title: Lapatinib in Endocrine-Resistant Metastatic Breast Cancer
Two thirds or more of breast cancers are dependent on estrogen for growth. We use a number of estrogen-blocking medicines for treatment of metastatic breast cancer. The treatment response to these agents is unpredictable, however, and approximately one-third of patients with metastatic breast cancer with receptors for estrogen or progesterone have no benefit from hormonal therapy. Nearly all patients with metastatic breast cancer will eventually become resistant to hormonal therapy despite the fact that the hormone receptors are still present.
Some cells make a different class of growth factor receptor called the Epidermal Growth Factor Receptor. There is a growing body of experimental evidence showing that breast cancer cells that make Epidermal Growth Factor Receptors are more resistant to hormonal therapy and have a poorer prognosis. Several investigators have found that the Epidermal Growth Factor Receptor can activate the estrogen receptor, even in the presence of estrogen-blocking drugs. Growth of these cells can be slowed by blockade of both Epidermal Growth Factor Receptor signaling and estrogen-receptor signaling. Lapatinib is a small molecule which can inhibit two different forms of the Epidermal Growth Factor Receptor. It has been studied in people with a number of different cancers, including breast cancer, and a safe dose and its common side effects have been defined.
Our hypothesis is that the Epidermal Growth Factor Receptor is the dominant receptor pathway used by breast cancers in our patients with hormone-resistant tumors. Drugs like lapatinib which block several forms of the Epidermal Growth Factor Receptor would best be able to reverse resistance to hormonal agents.
Read the detailed description
All patients must have stopped their endocrine two to four weeks or longer prior to entry on study. Upon enrollment, patients will begin lapatinib at 1500 mg once a day orally. The original endocrine therapy will resume two weeks later. The lapatinib will be continued for a maximum of 26 weeks.
A history, physical examination, blood counts, and chemistries will be done at baseline, and at regular intervals through the course of the study. A CT scan and bone scan will be done prior to treatment and at weeks 14 and 26. Assays for plasma DNA will be performed on blood sampled at baseline and at multiple time points throughout the course of treatment. Percutaneous biopsies will be taken in selected patients with accessible disease, 72 hours or less prior to the start of lapatinib, and again 13-15 days, and 27-29 days following the start of lapatinib. The day 13-15 biopsy will be done just prior to the resumption of the patient's endocrine therapy. Assays for phospho-ERK, phospho-Akt, Cyclin D1, Ki-67, and IRS-1 will be performed by conventional immunohistochemistry on the biopsied tissue.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Lapatinib
- Keywords
- breast cancer, endocrine therapy, drug resistance, lapatinib, epidermal growth factor receptor
- 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
Also called Tykerb
1500 mg po daily for 26 weeks or longer
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Subjects will continue on their prior endocrine therapy with the addition of lapatinib at 1500 mg once daily for 26 weeks or longer. Receives: Drug: Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the Response Rate and Progression Free Survival of Hormone Therapy-resistant Patients With Metastatic Breast Cancer Treated With the Same Continued Hormonal Agent With the Addition of Lapatinib.
A response is defined as stable disease or better at 26 weeks. Twenty two patients are evaluable for response
Measured: 26 weeks
Progression-free Survival
Progression-free survival is the time between date on study and progression based on RECIST criteria.
Measured: Up to 575 days
Secondary outcomes (3)
Determine the Toxicities of the Combination of the Hormonal Agent and Lapatinib in Patients With Metastatic Breast Cancer
Measured: 26 weeks
Determine Changes in Activation of Tumor Cell ERK and Akt, as Between the Hormonal Agent and Lapatinib Contributes to the Molecular Pharmacodynamic Effect Postulated Above.
Measured: 4 weeks
Determine Whether Changes in Plasma DNA Concentrations Are Predictive Markers of an Early Response to Lapatinib
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2005 (estimated)
- Study startJan 2006
- Primary completionOct 2011
- Study completionOct 2011
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gary Schwartz
- Sponsor type
- University, hospital or other
- Collaborators
- University of Colorado, Denver, North Shore University Hospital
- Responsible party
- Sponsor-investigator, Gary Schwartz, Dartmouth-Hitchcock Medical Center
- Investigators
- Gary N Schwartz, MD, Principal investigator, Norris Cotton Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00225758
- Sponsor's protocol ID
- D-0520
- Status last verified
- Jul 2018
- First submitted
- 22 Sep 2005
- Last updated
- 27 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lapatinib in Endocrine-Resistant Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00225758
- Acronym / sponsor ID
- D-0520
- Conditions
- Metastatic Breast Cancer
- Keywords
- breast cancer, endocrine therapy, drug resistance, lapatinib, epidermal growth factor receptor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Gary SchwartzUniversity, hospital or other
- Collaborators
- University of Colorado, Denver, North Shore University Hospital
- Study start
- Jan 2006
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 26 Sep 2005 (estimated)
- Results
- Posted 27 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Two thirds or more of breast cancers are dependent on estrogen for growth. We use a number of estrogen-blocking medicines for treatment of metastatic breast cancer. The treatment response to these agents is unpredictable, however, and approximately one-third of patients with metastatic breast cancer with receptors for estrogen or progesterone have no benefit from hormonal therapy. Nearly all patients with metastatic breast cancer will eventually become resistant to hormonal therapy despite the fact that the hormone receptors are still present.
Some cells make a different class of growth factor receptor called the Epidermal Growth Factor Receptor. There is a growing body of experimental evidence showing that breast cancer cells that make Epidermal Growth Factor Receptors are more resistant to hormonal therapy and have a poorer prognosis. Several investigators have found that the Epidermal Growth Factor Receptor can activate the estrogen receptor, even in the presence of estrogen-blocking drugs. Growth of these cells can be slowed by blockade of both Epidermal Growth Factor Receptor signaling and estrogen-receptor signaling. Lapatinib is a small molecule which can inhibit two different forms of the Epidermal Growth Factor Receptor. It has been studied in people with a number of different cancers, including breast cancer, and a safe dose and its common side effects have been defined.
Our hypothesis is that the Epidermal Growth Factor Receptor is the dominant receptor pathway used by breast cancers in our patients with hormone-resistant tumors. Drugs like lapatinib which block several forms of the Epidermal Growth Factor Receptor would best be able to reverse resistance to hormonal agents.
Detailed description
All patients must have stopped their endocrine two to four weeks or longer prior to entry on study. Upon enrollment, patients will begin lapatinib at 1500 mg once a day orally. The original endocrine therapy will resume two weeks later. The lapatinib will be continued for a maximum of 26 weeks.
A history, physical examination, blood counts, and chemistries will be done at baseline, and at regular intervals through the course of the study. A CT scan and bone scan will be done prior to treatment and at weeks 14 and 26. Assays for plasma DNA will be performed on blood sampled at baseline and at multiple time points throughout the course of treatment. Percutaneous biopsies will be taken in selected patients with accessible disease, 72 hours or less prior to the start of lapatinib, and again 13-15 days, and 27-29 days following the start of lapatinib. The day 13-15 biopsy will be done just prior to the resumption of the patient's endocrine therapy. Assays for phospho-ERK, phospho-Akt, Cyclin D1, Ki-67, and IRS-1 will be performed by conventional immunohistochemistry on the biopsied tissue.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: LapatinibSubjects will continue on their prior endocrine therapy with the addition of lapatinib at 1500 mg once daily for 26 weeks or longer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with histologically or cytologically proven metastatic breast cancer.
- Patients with either estrogen or progesterone receptor positivity on the most recently examined tumor biopsy.
- Patients must have most recently been using an anti-estrogen (tamoxifen, toremifene, raloxifene, or fulvestrant) or an aromatase inhibitor.
- Patients must have had either a partial response or better, or stable disease for 24 weeks or longer, followed by disease progression, on the current or most recent hormonal therapy for management of metastatic breast cancer.
- Patients must be enrolled within six weeks of defining disease progression on hormonal therapy.
Key exclusion criteria (9 listed)
- Patients may not have received an investigational agent within the prior four weeks.
- Patients may not have received trastuzumab within three weeks of study entry.
- Patients may not have had major surgery within the prior two weeks.
- Patients may not have Class III or IV heart failure as defined by the NYHA functional classification system.
- Patients may not have a left ventricular ejection fraction < 40% based on MUGA or echocardiogram.
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 |
|---|---|---|
| LapatinibAlso: Tykerb1500 mg po daily for 26 weeks or longer | Drug | 1 |
Primary outcome
Determine the Response Rate and Progression Free Survival of Hormone Therapy-resistant Patients With Metastatic Breast Cancer Treated With the Same Continued Hormonal Agent With the Addition of Lapatinib.
Time frame: 26 weeks
A response is defined as stable disease or better at 26 weeks. Twenty two patients are evaluable for response
Progression-free Survival
Time frame: Up to 575 days
Progression-free survival is the time between date on study and progression based on RECIST criteria.
3 secondary outcomes
Determine the Toxicities of the Combination of the Hormonal Agent and Lapatinib in Patients With Metastatic Breast Cancer
Time frame: 26 weeks
Determine Changes in Activation of Tumor Cell ERK and Akt, as Between the Hormonal Agent and Lapatinib Contributes to the Molecular Pharmacodynamic Effect Postulated Above.
Time frame: 4 weeks
Determine Whether Changes in Plasma DNA Concentrations Are Predictive Markers of an Early Response to Lapatinib
Time frame: 14 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Gary N Schwartz, MD principal investigator
Norris Cotton Cancer Center
3 sites in 1 country: 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 Metastatic Breast Cancer, run by Gary Schwartz at 3 sites in United States.
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 13 inclusion and 9 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 27 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
Yes. Results are posted in the registry (first posted 27 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Determine the Response Rate and Progression Free Survival of Hormone Therapy-resistant Patients With Metastatic Breast Cancer Treated With the Same Continued Hormonal Agent With the Addition of Lapatinib. (time frame: 26 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jul 2018.