Clinical trial: NCT00826241
Section: Alternatives
Subsections: Potential Benefits|Alternate Procedures Or Treatments

Treatment with lapatinib and temozolomide may help to control the disease. Future patients may benefit from what is learned. There may be no benefits for you in this study.

You may choose not to take part in this study. You may choose to receive other treatments for ependymoma that has come back (such as chemotherapy, radiation therapy, or a combination of both). You may choose to receive other investigational therapy, if available. You may choose not to have treatment for cancer at all. In all cases, you will receive appropriate medical care, including treatment for pain and other symptoms of cancer.
Clinical trial: NCT00826241
Section: Confidentiality
Subsections: Certificate Of Confidentiality|Will Your Medical Information Be Kept Private?

To help us protect your privacy, we have obtained a a Certificate of Confidentiality from the National Institutes of Health. The Certificate protects against the involuntary release of information about subjects collected during the course of our covered studies. The researchers involved in the studies cannot be forced to disclose the identity or any information collected in the study in any legal proceedings at the federal, state, or local level, regardless of whether they are criminal, administrative, or legislative proceedings. However, the subject or the researcher may choose to voluntarily disclose the protected information under certain circumstances. For example, if the subject or his/her guardian requests the release of information in writing, the Certificate does not protect against that voluntary disclosure. Furthermore, federal agencies may review our records under limited circumstances, such as a DHHS request for information for an audit or program evaluation or an FDA request under the Food, Drug and Cosmetics Act. The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others. This study may involve unpredictable risks to the participants.

We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
- The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people, or their agent(s)
Clinical trial: NCT00826241
Section: Duration of Study Involvement
Subsections: Study Visits|Length Of Study|End-Of-Study Visit|Long-Term Follow-Up Visit

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 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.

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.

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.

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 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. While you are on study, lapatinib will be provided at no cost to you. If lapatinib becomes FDA approved for the treatment of ependymoma while you are on study, you may have to pay for the remaining doses. You and/or your insurance provider will be responsible for the cost of temozolomide.  
Up to 58 patients will take part in this multicenter study. Up to (*insert local accrual ceiling*)
Clinical trial: NCT00826241
Section: Participant's Rights
Subsections: Consent/Authorization|Signature Of Participant Date

I understand the information in this consent form. I have had a chance to read the consent form for this study, or have had it read to me. I have had a chance to think about it, ask questions, and talk about it with others as needed. I give the study chair permission to enroll me on this study. By signing this consent form, I am not giving up any of my legal rights. I will be given a signed copy of this consent document.

PERSON OBTAINING CONSENT
I have discussed this clinical research study with the participant, using language that is understandable and appropriate. I believe that I have fully informed this participant of the nature of this study and its possible benefits and risks and that the participant understood this explanation.
Clinical trial: NCT00826241
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Will Be Enrolled At (**Insert Site Name**). Risks, Side Effects, And Discomforts To Participants|Temozolomide Side Effects|Common (Occurring In 3-20% Of Patients)|Pregnancy Related Risks

While on this study, you are at risk for side effects. These side effects will vary from person to person. The more commonly occurring side effects are listed in this form, as are rare but serious side effects that the drugs are known to cause. You should discuss these with the study doctor. You may also want to ask about uncommon side effects that have been observed in small numbers of patients but are not listed in this form. Many side effects go away shortly after treatment is stopped, but in some cases side effects may be serious, longlasting or permanent, and may even result in hospitalization and/or death.

| -   | fatigue   |
|-----|-----------|
| -   | headache  |
| -   | seizures  |  
Temozolomide may likely cause low white blood counts. This means that while you take the drug, there is more of a chance of getting an infection, including pneumonia.  
| -   | hair loss        |    |              |
|-----|------------------|----|--------------|
| -   | nausea           |    |              |
| -   | vomiting         | -  | constipation |
| -   | loss of appetite |    |              |  
Common (occurring in 3-20% of patients)  
| -   | arm and/or leg swelling                              |
|-----|------------------------------------------------------|
| -   | weakness (such as weakness on  one side of the body) |
| -   | confusion                                            |
| -   | dizziness                                            |
| -   | fever                                                |
| -   | memory problems and/or loss                          |
| -   | difficulty sleeping                                  |
| -   | drowsiness                                           |
| -   | anxiety                                              |
| -   | depression                                           |
| -   | abnormal muscle movements                            |  
| -   | itching                                                                                           |
|-----|---------------------------------------------------------------------------------------------------|
| -   | dry skin                                                                                          |
| -   | excess steroid in the  body (possible bruising  and/or increase in size  of the face and/or neck) |
| -   | diarrhea                                                                                          |
| -   | taste changes                                                                                     |
| -   | sores in the mouth                                                                                |
| -   | difficulty swallowing                                                                             |
| -   | abdominal pain                                                                                    |
| -   | weight gain                                                                                       |  
| -   | tickling/tingling  sensation                            |
|-----|---------------------------------------------------------|
| -   | unusual manner of  walking                              |
| -   | joint, muscle, and/or  back pain                        |
| -   | abnormal vision (such  as blurry and/or double  vision) |
| -   | head cold                                               |
| -   | cough                                                   |
| -   | sore throat                                             |  
| /coordination   |                         |    |                              |
|-----------------|-------------------------|----|------------------------------|
| -               | partial paralysis       |    |                              |
| -               | skin rash               | -  | female breast pain           |
| -               | loss of urinary control |    |                              |
| -               | urinary tract infection |    |                              |
| -               | frequent urination      | -  | inflammation of the  sinuses |
| -               | difficulty breathing    |    |                              |
| -               | allergic reaction       |    |                              |
| -               | viral infection         |    |                              |  
Temozolomide may commonly cause low blood cell counts (red blood cells, and platelets). You may have problems with bleeding and /or bruising. You may become anemic, fatigued, and/or shortness of breath. You may need a blood transfusion.  
| Rare but serious (occurring in fewer than 3% of patients) - hallucinations - nervous system disease (possible  pain and/or weakness)  - nerve damage (possible  numbness, tingling, and pain) - damage from radiation (such as  skin damage)  - severe skin damage with loss of a  large portion of skin  - severe skin damage with  inflammation of the bowel  - allergic skin reaction - high blood sugar  (possible diabetes)  - low blood levels of  potassium (possible  weakness) - bone marrow disease  where not enough blood  cells are made - weight loss - fever due to low white  blood cell counts  - bruising  - bleeding   | -                                                                                              | lung inflammation   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------|---------------------|
| -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | flu-like symptoms                                                                              |                     |
| -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | injection site reactions  (skin redness, irritation,  pain, itching, swelling,  and/or warmth) |                     |
| -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | opportunistic infection                                                                        |                     |
| -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | herpes infection causing  painful skin rash  (shingles)                                        |                     |
| -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | new occurrence of cancer  (including myeloid  leukemia)                                        |                     |
| -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | severe allergic reaction                                                                       |                     |  
The following side effects have been reported in research studies with temozolomide. It is unclear if these side effects were caused by temozolomide, but they may be:  
| is unclear if these side effects were caused by temozolomide, but they may be: - hole in the stomach and/or  intestines, which may cause the  contents to leak  - inflammation of the gallbladder - death - dehydration - inflammation of the  pancreas - abnormal kidney test  (possible decreased  kidney function) - nosebleeds - deficient oxygen in the  blood and tissues  - presence of bacteria or  their toxins in blood or  tissues (sepsis) Lapatinib Side Effects   |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
Likely (occurring in more than 20% of patients)  
| -                         | pain, swelling, blistering, and/or   | -        | skin rash   |
|---------------------------|--------------------------------------|----------|-------------|
| redness of the hands/feet | -                                    | diarrhea |             |
| -                         | nausea                               |          |             |
| -                         | vomiting                             |          |             |  
| -   | abnormal liver test  (possible liver damage)    |
|-----|-------------------------------------------------|
| -   | jaundice (yellowing  and/or darkening of  skin) |  
Lapatinib may likely cause low blood cell counts (red blood cells and white blood cells). This means that while you take the drug, there is more of a chance of getting an infection, including pneumonia. You may become anemic and/or have problems with bleeding, bruising, fatigue, and/or shortness of breath. You may need a blood transfusion.

| -   | fatigue             |
|-----|---------------------|
| -   | difficulty sleeping |
| -   | flushing            |
| -   | dry skin            |
| -   | acne                |
| -   | itchy skin          |
| -   | abdominal pain      |
| -   | abdominal bloating  |  
Lapatinib may commonly cause low platelet counts. You may have problems with bleeding and/or bruising. You may need a blood transfusion if a problem with bleeding occurs.  
| -   | early satiety (feeling  full)       |
|-----|-------------------------------------|
| -   | inflammation of the  mucus membrane |
| -   | mouth sores                         |
| -   | upset stomach                       |
| -   | poor appetite                       |
| -   | weight loss                         |
| -   | gas                                 |  
| -   | heartburn            |
|-----|----------------------|
| -   | taste change         |
| -   | arm and/or leg pain  |
| -   | general weakness     |
| -   | back pain            |
| -   | difficulty breathing |
| -   | headache             |
| -   | flu-like symptoms    |  
Rare but serious (occurring in fewer than 3% of patients)
- decreased heart function
- chest pain caused by a heart spasm  
- irregular heartbeat  
- liver damage  
- lung disease  
- lung inflammation  
The following side effects have been reported in research studies with lapatinib. It is unclear if these side effects were caused by lapatinib, but they may be:  
| -   | low volume of blood                                           |
|-----|---------------------------------------------------------------|
| -   | inflammation of the  blood vessels                            |
| -   | liver failure                                                 |
| -   | abnormal liver test  (possible liver damage)                  |
| -   | chronic inflammation of  the liver                            |
| -   | arm and/or leg swelling                                       |
| -   | general pain, joints and  muscles                             |
| -   | facial swelling                                               |
| -   | blurred vision                                                |
| -   | kidney failure                                                |
| -   | kidney impairment                                             |
| -   | increased creatinine  blood level (possible  kidney problems) |
| -   | pulmonary embolism  (blood clot to lung)                      |
| -   | cough                                                         |  
| -   | heart failure                                                |
|-----|--------------------------------------------------------------|
| -   | low blood pressure                                           |
| -   | enlarged heart                                               |
| -   | high blood pressure                                          |
| -   | tumor growth in the heart                                    |
| -   | inflammation of the membrane  surrounding the heart          |
| -   | heart attack                                                 |
| -   | blockage of a blood vessel that  supplies blood to the heart |
| -   | irregular heartbeat                                          |
| -   | infection of the heart                                       |
| -   | inflammation of the muscle of  the heart                     |
| -   | coma                                                         |
| -   | bleeding in the brain                                        |
| -   | fever                                                        |
| -   | dizziness                                                    |
| -   | shock                                                        |
| -   | abnormal behavior                                            |
| -   | confusion                                                    |  
| -   | low blood sugar                                                                    |
|-----|------------------------------------------------------------------------------------|
| -   | low blood levels of  potassium (possible  weakness)                                |
| -   | high blood sugar  (possible diabetes)                                              |
| -   | low blood level of  sodium (possible  headache, confusion,  seizures, and/or coma) |
| -   | low blood levels of  phosphate (possible  bone damage)                             |
| -   | decreased thyroid  hormones                                                        |
| -   | inflammation of the  thyroid gland                                                 |
| -   | constipation                                                                       |
| -   | inflammation of the  stomach lining                                                |
| -   | blockage of intestine                                                              |  
- low blood supply to the brain tissue
- fainting
- degenerative nerve disease
- painful fingers and feet/toes
- skin changes including nail changes and/or hives
- hand-foot syndrome (pain, swelling, blistering, and/or redness of the hands and/or feet)
- shingles (painful skin rash)
- inflammation of the tissue underneath the skin (cellulitis)  
| -   | infection in stomach  and/or intestines                          |
|-----|------------------------------------------------------------------|
| -   | inflammation of the  large bowels                                |
| -   | bloody stools                                                    |
| -   | bloody vomit                                                     |
| -   | break/slit of the tissue of  the anus                            |
| -   | mouth bleeding                                                   |
| -   | dehydration                                                      |
| -   | bleeding in the digestive  system                                |
| -   | painful urination                                                |
| -   | urinary tract infection                                          |
| -   | (DVT) a blood clot  within a large vein (in  the legs or pelvis) |
| -   | (DIC) excessive clotting  or bleeding throughout  the body       |  
- nose bleeds  
- respiratory failure  
(inability to breathe)  
- pus-filled areas in the  
lung  
- coughing up blood  
- swelling of the throat or  
voice box  
- difficulty and/or painful  
swallowing  
- respiratory tract  
infection  
- allergic reaction  
- sudden death  
- viral infection  
- incomplete or faulty  
development of a body organ (aplasia)  
There is a chemical that is present in lapatinib in small quantities. This chemical by itself may cause changes to genes (DNA--the genetic material of cells) that may lead to an increased chance of developing new cancer or tumors.  
Using the **study drugs together** may cause side effects that are not seen when each is given alone. Because certain other drugs can interact with temozolomide, review all drugs that you are taking with your healthcare provider, including those that you take without a prescription.  
Blood draws may cause pain, bleeding, and/or bruising. You may faint and/or develop an infection with redness and irritation of the vein at the site where blood is drawn. Frequent blood collection may cause anemia (low red blood cell count), which may create a need for blood transfusions.  
Questionnaires may contain questions that are sensitive in nature. You may refuse to answer any question that makes you feel uncomfortable. If you have concerns after completing the questionnaire, you are encouraged to contact your doctor or the study chair.

Because taking part in this study can result in risks to an unborn or breastfeeding baby, you should not become pregnant, breastfeed a baby, or father a child while on this study. You must use birth control during the study if you are sexually active. Birth Control Specifications: Women who are able to become pregnant and men who are able to father a child must use birth control while on study and for 6 months after the last dose of study drugs. Acceptable forms of birth control include birth control pills and/or condoms. Males: Tell the doctor right away if your partner becomes pregnant or suspects pregnancy. Females: If you are pregnant, you will not be enrolled on this study. If you become pregnant or suspect that you are pregnant, you must tell your doctor right away. Getting pregnant may result in your removal from this study.
Clinical trial: NCT00826241
Section: Procedures
Subsections: Description Of Study The Study Drugs|Screening Tests|Study Drug Administration

Temozolomide is designed to kill cancer cells by damaging 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 Her2/neu receptor and the epidermal growth factor receptor (EGFR).

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. If you have had some of them within the past 14 days, they may not need to be repeated. The following tests and procedures will be performed:
- You will be asked about any drugs you may be taking.  
- Your complete medical history will be recorded.  
- You will have a complete physical exam, including measurement of your vital signs
(heart rate, temperature, breathing rate, and blood pressure), height, and weight.  
- You will be asked how well you are able to perform the normal activities of daily living (performance status).  
- You will have a neurological exam (a test to check your level of brain and nerve function).  
- Blood (about 2-3 tablespoons) will be drawn for routine tests. This routine blood draw will also include a pregnancy test for women who are able to have children. If you are a woman who is able to have children, the pregnancy test must be negative in order for you to take part in this study.  
- Blood (about 1 teaspoon) will be drawn for tests to check your blood's ability to clot.  
- If you are taking anti-seizure drugs, blood (about 1 teaspoon) will be drawn to check the level of anti-seizure drug in your blood.  
- You will have an magnetic resonance imaging (MRI) scan to measure the tumor.  
- You will have an electrocardiogram (ECG--a test to measure the electrical activity of the heart).  
- You will have either a multigated acquisition (MUGA) scan (if the doctor thinks it is needed) or an echocardiogram to check your heart function.  
- You will be asked to complete a questionnaire about your quality of life. The questionnaire will take about 5 minutes to complete.  
- Samples of tumor tissue (such as disease diagnosis slides or tumor tissue leftover from a previous biopsy) is needed to verify your diagnosis. If there is extra tumor tissue available, this will be used to test the biomarkers. Biomarkers are chemical "markers" in the blood/tissue that may be related to your reaction to the study drug.  
The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you.

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.
Clinical trial: NCT00826241
Section: Purpose of Research
Subsections: Purpose Of Study

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.