Central Nervous System MetastasesPhase 2NCT00098605
Lapatinib in Treating Brain Metastases in Patients With Stage IV Breast Cancer and Brain Metastases
A Phase 2 study testing lapatinib ditosylate, laboratory biomarker analysis and quality-of-life assessment in people with Central Nervous System Metastases and HER2-positive Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. This phase II trial is studying how well lapatinib works in treating brain metastases in patients with stage IV breast cancer and brain metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Nervous System Metastases, HER2-positive Breast Cancer, Male Breast Cancer
- What is being tested?
- lapatinib ditosylate, laboratory biomarker analysis and quality-of-life assessment
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2004to Sep 2006
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease
- HER2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with HER2 gene amplification by fluorescent in situ hybridization (FISH), or HER2 gene amplification by FISH alone (in patients whose tumor blocks were not assessed by IHC); patients with tumors that are 2+ by IHC but negative by FISH assay are ineligible
- At least one measurable lesion in the CNS, defined as any lesion >= 10 mm in longest dimension on T1-weighted, gadolinium-enhanced MRI
- One of the following:
- Cohort 1: Prior treatment of CNS metastases with whole brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS), OR;
- Cohort 2: Asymptomatic CNS metastases discovered on a screening radiological study without prior WBRT or SRS
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- Disease progression in the CNS, as assessed by at least one of the following:
- New neurological signs or symptoms
- New lesions in the CNS on an imaging study
- Progressive lesions on an imaging study
- Note: patients with progressive lesions are not required to meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progression in order to be eligible for this study
- Prior treatment with trastuzumab, either alone or in combination with chemotherapy is required; trastuzumab will be discontinued at least 2 weeks prior to enrollment on study; note: patients who have documented CNS-only metastases are not required to have had prior treatment with trastuzumab; in this situation, the absence of extra-CNS disease must be documented with a physical examination, CT scan of the chest, abdomen, and pelvis, and bone scan
- At least 2 weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or hormonal therapy for cancer, and sufficiently recovered or stabilized from side effects associated with prior therapy; concurrent treatment with bisphosphonates is permitted
- At least 3 weeks since major surgical procedures
- At least 2 weeks since last dose of trastuzumab
- Life expectancy >= 12 weeks
- ECOG performance status 0-2 (Karnofsky >= 60%)
- Hemoglobin >= 9 g/dL (after transfusion if needed)
- Platelets >= 50 x 10^9/L
- Albumin >= 2.5 g/dL
- Serum bilirubin =< 1.5 x ULN unless due to Gilbert's syndrome
- AST and ALT =< 5 x ULN
- Serum creatinine =< 1.5 mg/dL or calculated creatinine clearance >= 25 mL/min (calculated by the Cockcroft and Gault method)
- Cardiac ejection fraction within institutional normal limits, as assessed by echocardiogram or MUGA scan
- Women of childbearing potential are eligible for this study provided they agree to one of the following:
- Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of GW572016 until 28 days after the final dose of GW572016; or
- Consistent and correct use of one of the following acceptable methods of birth control:
- Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; or
- Implants of levonorgestrel
- Injectable progestogen
- Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; or
- Oral contraceptives (either combined or progestogen only)
- Barrier methods including diaphragm or condom with a spermicide Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Able to swallow and retain oral medications
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
- Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment
- Patients may not be receiving any other investigational agents
- Patients may not be receiving concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer; concurrent treatment with bisphosphonates is allowed
- Patients with leptomeningeal carcinomatosis as the only site of CNS involvement will be excluded from this clinical trial, because disease is not measurable, and standard treatment options may differ
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016
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- Concurrent treatment with medications that are either inducers or inhibitors of CYP3A4 is prohibited; some common examples are phenytoin, carbamazepine, and phenobarbital; if a patient requires an anticonvulsant, valproic acid or levetiracetam (Keppra) may be substituted, under the direction of his/her treating physician and/or neurologist
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel; subjects with active ulcerative colitis are also excluded
- History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast
- Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel
- Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical or psychiatric disorder that would interfere with the subject's safety
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent
- Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel, CNS vasculitis, or malignant hypertension
- Active cardiac disease, defined as:
- History of uncontrolled or symptomatic angina
- History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
- Myocardial infarction < 6 months from study entry
- Uncontrolled or symptomatic congestive heart failure
- Ejection fraction below the institutional normal limit
- Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
- Active or uncontrolled infection
- History of other malignancy, except for curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix; subjects with other malignancies who have been disease-free for at least 5 years are eligible
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with GW572016
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase 2 Study of GW572016 for Brain Metastases in Patients With HER2-Positive Breast Cancer
Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. This phase II trial is studying how well lapatinib works in treating brain metastases in patients with stage IV breast cancer and brain metastases.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the objective response rate in the central nervous system (CNS) (complete plus partial responses), as assessed by standard MRI, to oral GW572016 among patients with progressive brain metastases from HER2-positive breast cancer.
SECONDARY OBJECTIVES:
- To evaluate the site of first failure (CNS, extra-CNS, both, or death) and overall survival of patients treated with GW572016 for brain metastases.
II. To evaluate the overall objective response rate (complete plus partial response) and time to first progression at any site.
III. To assess quality of life (QOL), neurologic QOL, and cause of death in patients treated with GW572016 for brain metastases.
IV. To determine the qualitative and quantitative toxicities associated with oral GW572016, given at a dose of 750 mg orally, twice daily.
- To evaluate the sensitivity of PET with dedicated brain sequences to detect brain metastases from breast cancer.
VI. To explore the relationship between decline in PET uptake at 1 week and decline in PET uptake at 8 weeks.
VII. To characterize the vessel patterns seen on MRI at baseline, 8 weeks, and 16 weeks of treatment with GW572016.
VIII. To describe changes in serum HER2 ECD over time. IX. To describe the baseline EGFR, HER2, IGF-IR, and degree of HER2 gene amplification in primary tumor blocks.
OUTLINE: This is an open-label, multicenter study.
Patients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and at 8 weeks.
Patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 0.5-1.5 years.
- Conditions
- Central Nervous System Metastases, HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer, Tumors Metastatic to Brain
- Being tested
- lapatinib ditosylate, laboratory biomarker analysis, quality-of-life assessment, questionnaire administration
- Medical subject headings
- Breast Neoplasms, Male, Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lapatinib ditosylateDrug
Also called GSK572016, GW-572016, GW2016, Lapatinib
Given orally
laboratory biomarker analysisOther
Correlative studies
quality-of-life assessmentProcedure or surgery
Also called quality of life assessment
Ancillary studies
questionnaire administrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (lapatinib ditosylate) | Experimental | Patients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: lapatinib ditosylate; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment; Other: questionnaire administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate defined as the percentage of patients with a complete response (CR) or partial response (PR) in the CNS
A 95% confidence interval (CI) for percent of patients with CNS response will be calculated if the study does not terminate accrual early. The method of Atkinson and Brown will be used to calculate the CI conditional on the sequential design.
Measured: Up to 5 years
Secondary outcomes (7)
Objective response in non-CNS sites
A 95% CI for percent of patients with CNS response will be calculated if the study does not terminate accrual early. The method of Atkinson and Brown will be used to calculate the CI conditional on the sequential design.
Measured: Up to 5 years
Site of first progression
Measured: At the time of disease progression
Time to progression (TTP)
The time to progression will be summarized using a Kaplan-Meier survival curve.
Measured: From study entry to the first documented evidence of disease progression, assessed up to 5 years
Overall survival
Overall survival for each cohort will be summarized using a Kaplan-Meier survival curve.
Measured: From study entry until death due to any cause, assessed up to 5 years
Quality of life assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core Cancer Module (QLQ-C30) and EORTC Brain Cancer Module (BCM-20)
Changes from baseline will be summarized for the total score and subscale scores. Responses will be scored and reported according to published methods. The baseline and change scores will be characterized descriptively.
Measured: Baseline
Quality of life assessed using the EORTC QLQ-C30 and EORTC BCM-20
Changes from baseline will be summarized for the total score and subscale scores. Responses will be scored and reported according to published methods. The baseline and change scores will be characterized descriptively.
Measured: Week 8
Cause of death classified as being due to systemic disease progression, primarily due to CNS disease progression, primarily due to treatment-related toxicity, or unrelated to the subject's breast cancer diagnosis
The proportion of patients who fall into each category will be tabulated.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2004 (estimated)
- Study startOct 2004
- Primary completionSep 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System MetastasesStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Eric Winer, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098605
- Sponsor's protocol ID
- NCI-2012-02934
- Other IDs
- DFCI 04-199
- Status last verified
- Jun 2013
- First submitted
- 7 Dec 2004
- Last updated
- 6 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of GW572016 for Brain Metastases in Patients With HER2-Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT00098605
- Acronym / sponsor ID
- NCI-2012-02934
- Conditions
- Central Nervous System Metastases, HER2-positive Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer, Tumors Metastatic to Brain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2004
- Primary completion
- Sep 2006 (actual)
- First posted
- 8 Dec 2004 (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.
Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. This phase II trial is studying how well lapatinib works in treating brain metastases in patients with stage IV breast cancer and brain metastases.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the objective response rate in the central nervous system (CNS) (complete plus partial responses), as assessed by standard MRI, to oral GW572016 among patients with progressive brain metastases from HER2-positive breast cancer.
SECONDARY OBJECTIVES:
- To evaluate the site of first failure (CNS, extra-CNS, both, or death) and overall survival of patients treated with GW572016 for brain metastases.
II. To evaluate the overall objective response rate (complete plus partial response) and time to first progression at any site.
III. To assess quality of life (QOL), neurologic QOL, and cause of death in patients treated with GW572016 for brain metastases.
IV. To determine the qualitative and quantitative toxicities associated with oral GW572016, given at a dose of 750 mg orally, twice daily.
- To evaluate the sensitivity of PET with dedicated brain sequences to detect brain metastases from breast cancer.
VI. To explore the relationship between decline in PET uptake at 1 week and decline in PET uptake at 8 weeks.
VII. To characterize the vessel patterns seen on MRI at baseline, 8 weeks, and 16 weeks of treatment with GW572016.
VIII. To describe changes in serum HER2 ECD over time. IX. To describe the baseline EGFR, HER2, IGF-IR, and degree of HER2 gene amplification in primary tumor blocks.
OUTLINE: This is an open-label, multicenter study.
Patients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline and at 8 weeks.
Patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 0.5-1.5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (lapatinib ditosylate) | Experimental | Drug: lapatinib ditosylate, Other: laboratory biomarker analysis, Procedure: quality-of-life assessment, Other: questionnaire administrationPatients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease
- HER2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with HER2 gene amplification by fluorescent in situ hybridization (FISH), or HER2 gene amplification by FISH alone (in patients whose tumor blocks were not assessed by IHC); patients with tumors that are 2+ by IHC but negative by FISH assay are ineligible
- At least one measurable lesion in the CNS, defined as any lesion >= 10 mm in longest dimension on T1-weighted, gadolinium-enhanced MRI
- One of the following:
- Disease progression in the CNS, as assessed by at least one of the following:
Key exclusion criteria (23 listed)
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
- Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or who have unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment
- Patients may not be receiving any other investigational agents
- Patients may not be receiving concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of their cancer; concurrent treatment with bisphosphonates is allowed
- Patients with leptomeningeal carcinomatosis as the only site of CNS involvement will be excluded from this clinical trial, because disease is not measurable, and standard treatment options may differ
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 |
|---|---|---|
| lapatinib ditosylateAlso: GSK572016, GW-572016, GW2016, LapatinibGiven orally | Drug | Treatment (lapatinib ditosylate) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (lapatinib ditosylate) |
| quality-of-life assessmentAlso: quality of life assessmentAncillary studies | Procedure or surgery | Treatment (lapatinib ditosylate) |
| questionnaire administrationAncillary studies | Other | Treatment (lapatinib ditosylate) |
Primary outcome
Objective response rate defined as the percentage of patients with a complete response (CR) or partial response (PR) in the CNS
Time frame: Up to 5 years
A 95% confidence interval (CI) for percent of patients with CNS response will be calculated if the study does not terminate accrual early. The method of Atkinson and Brown will be used to calculate the CI conditional on the sequential design.
7 secondary outcomes
Objective response in non-CNS sites
Time frame: Up to 5 years
Site of first progression
Time frame: At the time of disease progression
Time to progression (TTP)
Time frame: From study entry to the first documented evidence of disease progression, assessed up to 5 years
Overall survival
Time frame: From study entry until death due to any cause, assessed up to 5 years
Quality of life assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core Cancer Module (QLQ-C30) and EORTC Brain Cancer Module (BCM-20)
Time frame: Baseline
Quality of life assessed using the EORTC QLQ-C30 and EORTC BCM-20
Time frame: Week 8
Cause of death classified as being due to systemic disease progression, primarily due to CNS disease progression, primarily due to treatment-related toxicity, or unrelated to the subject's breast cancer diagnosis
Time frame: Up to 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2013.
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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.
Eric Winer principal investigator
Dana-Farber Cancer Institute
1 site 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 ditosylate, laboratory biomarker analysis and quality-of-life assessment in people with Central Nervous System Metastases and HER2-positive Breast Cancer, run by National Cancer Institute (NCI) at 1 site 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 35 inclusion and 23 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: finished, as of the sponsor's last update on 6 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Objective response rate defined as the percentage of patients with a complete response (CR) or partial response (PR) in the CNS (time frame: Up to 5 years). 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 6 Jun 2013.