- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00098605
Lapatinib in Treating Brain Metastases in Patients With Stage IV Breast Cancer and Brain Metastases
A Phase 2 Study of GW572016 for Brain Metastases in Patients With HER2-Positive Breast Cancer
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. 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:
I. 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.
V. 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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (lapatinib ditosylate)
Patients receive oral lapatinib twice daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Ancillary studies
Ancillary studies
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response in non-CNS sites
Time Frame: Up to 5 years
|
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.
|
Up to 5 years
|
Site of first progression
Time Frame: At the time of disease progression
|
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
|
The time to progression will be summarized using a Kaplan-Meier survival curve.
|
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
|
Overall survival for each cohort will be summarized using a Kaplan-Meier survival curve.
|
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
|
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.
|
Baseline
|
Quality of life assessed using the EORTC QLQ-C30 and EORTC BCM-20
Time Frame: Week 8
|
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.
|
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
|
The proportion of patients who fall into each category will be tabulated.
|
Up to 5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Eric Winer, Dana-Farber Cancer Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Neoplastic Processes
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Breast Neoplasms
- Neoplasm Metastasis
- Brain Neoplasms
- Breast Neoplasms, Male
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Lapatinib
Other Study ID Numbers
- NCI-2012-02934
- DFCI 04-199
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HER2-positive Breast Cancer
-
Mersana TherapeuticsRecruitingHER2-positive Breast Cancer | HER2-positive Gastric Cancer | HER2-positive Non-Small Cell Lung Cancer | HER2-positive Colorectal Cancer | HER2-positive Tumors | HER2 Low Breast CancerUnited States
-
QuantumLeap Healthcare CollaborativeRecruitingSolid Tumor | Metastatic Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | HER2-positive Breast Cancer | Solid Tumor, Adult | Solid Carcinoma | HER2-positive Metastatic Breast Cancer | Progesterone Receptor-positive Breast Cancer | HER2-negative Breast Cancer | Estrogen Receptor Positive... and other conditionsUnited States
-
MacroGenicsApproved for marketingHER2-positive Breast Cancer | HER2-positive Carcinoma
-
Spanish Breast Cancer Research GroupSeagen Inc.RecruitingHER2-positive Metastatic Breast Cancer | Locally Advanced HER2 Positive Breast CarcinomaSpain
-
Cancer Trials IrelandCompletedBreast Cancer | HER2 Positive Breast Cancer | HER2 Negative Breast CancerIreland
-
Enliven TherapeuticsRecruitingColorectal Cancer | HER2-positive Breast Cancer | HER2-positive Gastric Cancer | HER2 Amplification | HER2 Positive Solid TumorsUnited States
-
Daiichi SankyoRecruitingBreast Cancer | Advanced Cancer | HER2-positive Breast Cancer | HER2-low Breast CancerChina
-
University of ArizonaPfizerCompletedBreast Cancer | Metastatic Breast Cancer | HER2-positive Breast Cancer | Recurrent Breast Cancer | HER2 Positive Breast Carcinoma | Breast Cancer StageUnited States
-
Clovis Oncology, Inc.TerminatedBreast Cancer | Metastatic Breast Cancer | Estrogen Receptor Positive | Triple Negative | HER2 | HER2 Positive | MBC | ERUnited States
-
Ruth O'ReganUniversity of Rochester; Puma Biotechnology, Inc.RecruitingBreast Cancer | HER2-positive Breast Cancer | ER Positive Breast Cancer | PR-Positive Breast CancerUnited States
Clinical Trials on laboratory biomarker analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States