The goal of this clinical research study is to learn if lapatinib when given in combination with temozolomide can help to control ependymoma that has come back after treatment. The safety of this combination will also be studied.
The Study Drugs: Temozolomide is designed to kill cancer cells by damaging deoxyribonucleic acid (DNA) (the genetic material of cells). This could cause the tumor cells to die. Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the human epidermal growth factor receptor 2 (Her2/neu) receptor and the epidermal growth factor receptor (EGFR). Study Drug Administration: If you are found to be eligible to take part in this study, every day, you will take lapatinib by mouth once a day in the morning. You should take lapatinib 1 hour before or 1 hour after eating, with at least 1 cup (about 8 oz.) of water. On Days 1-7 and 15-21 of each cycle, you will take temozolomide by mouth 1 time each day. You will start to take a lower dose of temozolomide for the first 2 cycles, then take a higher dose for Cycles 3 and beyond if you tolerate the treatment. It should be taken at least 2 hours before and 2 hours after eating with 1 cup (about 8 oz.) of water. You should swallow temozolomide and/or lapatinib whole, one right after the other, without chewing either of the study drugs. If you vomit while taking temozolomide and lapatinib, you cannot take more capsules before the next scheduled dose. You should report any missed pills or trouble you have with taking the pills to your study doctor. Your study doctor will give you a form (patient diary) to fill out to keep track of your treatment. You will be asked to return your completed diary and pill bottles at each visit with your doctor. Each study "cycle" is 28 days. Study Visits: Every 2 weeks, blood (about 2-3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot. Every 8 weeks, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your vital signs. * You will have a neurological exam. * Your performance status will be recorded. * You will be asked about any drugs you may be taking and if you have experienced any side effects. * You will complete the quality of life questionnaire. * You will have an magnetic resonance imaging (MRI) scan to check the status of the disease. * You will have either a multi-gated acquisition scan (MUGA) scan (if the doctor thinks it is needed) or an echocardiogram. Length of Study: You will be on study treatment for up to 2 years. You will be taken off study treatment early if the disease gets worse or you experience intolerable side effects. After you are off study, you may be able to continue taking lapatinib for as long as the doctor thinks it is in your best interest. Your doctor will discuss this with you. End-of-Study Visit: After you go off study treatment, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed: * You will have a physical exam. * Your performance status will be recorded. * You will be asked about any drugs you may be taking and if you have experienced any side effects. * You will have a neurological exam. * Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot. * You will complete the questionnaire. * You will have an MRI scan to check the status of the disease. * You will have either a MUGA scan (if the doctor thinks it is needed) or an echocardiogram. Long-Term Follow-up Visit: If you go off treatment (having completed the maximum 24 months on study drug treatment) and have stable disease or response, you will have an MRI scan to check the status of the disease every 2 months for first year after you are off study, then every 3 months for the second year, then every 4 months for the third year, and then every 6 months from then on. If you continue taking lapatinib after you have completed up to 24 months on study treatment, you will have a clinic visit and an MRI scan to check the status of the disease every 2 months for as long as the doctor thinks it is needed. At the clinic visits, you will be asked how you are doing. If you went off study treatment because the disease got worse or you experienced intolerable side effects, after the end-of-study visit, the study staff will call you every 3 months from then on to check how you are doing. Each phone call will take about 5 minutes. This is an investigational study. Temozolomide is Food and Drug Administration (FDA) approved or commercially available for the treatment of tumors of the nervous system. Lapatinib is FDA approved and commercially available for the treatment of breast cancer. However, lapatinib is not FDA approved for the treatment of brain tumors. The use of lapatinib with temozolomide in the treatment of brain tumors and spinal tumors is investigational. Up to 50 patients will take part in this multicenter study. Up to 30 will be enrolled at MD Anderson.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle.
Starting dose 1250 mg daily by mouth.
University of California, San Francisco
San Francisco, California, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
Time to Progression
Time to progression defined as progressive disease, toxicity at a level of severity that precludes the patient continuing on the protocol, or death. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Time frame: Assessed every two months till disease progression, up to 4 years
Number of Participants With an Overall Response (Complete Response or Partial Response) Assessed by the MacDonald Criteria
Anti-tumor activity as determined by the overall response (Complete response (CR) or partial response (PR)) was assessed by the MacDonald criteria. Complete response is complete resolution of all lesions. The patient cannot be on any corticosteroids with the exception of adrenal replacement doses. Partial response is ≥50% reduction in the sum of products of all measurable lesions over baseline sum observed using the same techniques as baseline. The patient must be on a stable or decreased dose of corticosteroids to be evaluable for response.
Time frame: 4 weeks
Number of Participants With Serious and Non-Serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Date treatment consent signed to date off study, approximately 111 months and 26 days
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University of Texas MD Anderson Cancer Center
Houston, Texas, United States
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, United States