Clinical trial: NCT02255461
Section: Alternatives
Subsections: What Other Choices Do I Have If I Do Not Take Part In This Study?|What Is The Usual Approach To **My Type Of Cancer?**|What Are My Other Choices If I Do Not Take Part In This Study?

If you decide not to take part in this study, you will not be able to take part in the main research study. You do have choices. For example:
- you may choose to take part in a different study, if one is available

You are being asked to take part in this research study because you have a brain tumor that has grown or come back or not responded to the usual treatment. People who are not in a study are usually treated with surgery, chemotherapy, radiation or other investigational agents. Sometimes, combinations of these are used and your study doctor can explain which may be best for you. These treatments can reduce symptoms and may stop the tumor from growing for several months or more.

If you decide not to take part in this study, you have other choices. Please talk to your doctor about these other options. For example:
- You may choose to have the usual approach described above
- You may choose to take part in a different research study, if one is available - Or you may choose not to be treated for cancer but you may want to receive comfort care to relieve symptoms.
Clinical trial: NCT02255461
Section: Confidentiality
Subsections: Who Will Know About My Participation In This Screening Study?|Who Will See My Medical Information?

Every effort will be made to keep your study record private. However, we cannot guarantee total privacy. All records related to your involvement in this screening study will be stored in locked research files at: *(hospital name).* Your identity in these records will be indicated by a unique number rather than by your name, and the information linking these case numbers with your identity will be kept separate from the screening records. Your personal information may be given out if required by law. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used. Organizations that may look at and/or copy your medical records for screening, quality assurance, and data analysis include:  
- Your referring physician.  
- The local Institutional Review Board - The Pediatric Brain Tumor Consortium, which coordinates this study - The National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), involved in keeping screening safe for people
- Representatives from pharmaceutical collaborators, such as the Pfizer company that supplies PD-0332991(IBRANCE)
- University of California, San Francisco
A description of this clinical trial may be available on http://www.ClinicalTrials.gov. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.

Your privacy is very important to us and the researchers will make every effort to protect it. Your personal information may be given out if required by law. However, the researchers will do their best to make sure that any information that is released will not identify you. Some of your health information, and/or information about your specimen, from this study will be kept in a central database for research.  
There are organizations that may look at and/or receive copies of your medical records for research, quality assurance, and data analysis. Some of these organizations are:
- The study sponsor and the representatives from the pharmaceutical collaborator (Pfizer) who manufactures PD-0332991 (IBRANCE)
- The local Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting people who take part in the study.  
- The Pediatric Brain Tumor Consortium, who coordinates this study - Federal agencies such as the Food and Drug Administration (FDA), the Office of Human Research Protections (OHRP) and the National Cancer Institute (NCI) in the U.S., and similar ones if other countries are involved in the study.
Coded patient data and images from brain scans will be transmitted over the Internet to be analyzed by other PBTC researchers. The PBTC has procedures (data encryption) in place to make electronic transmission of research information as secure as possible. The data security involves coding the data in a way that only the authorized receiver can decode the data. The method used to transfer information is more secure than many methods used by financial institutions when conducting business over the Internet.
Clinical trial: NCT02255461
Section: Duration of Study Involvement
Subsections: How Long Will I Be In The Study?|How Long Will I Be In This **Study?**

Since this is just a screening procedure, your involvement in this study will be minimal. The screening test will be done as soon as possible after you sign this consent. The results will be given to your doctor who will discuss them with you and talk about the next steps.

You will receive PD-0332991 (IBRANCE) for 26 courses (about 2 years). If you have benefited from receiving PD-0332991 (IBRANCE), and the study doctor agrees, you may be able to continue taking PD-0332991 (IBRANCE) for all 26 courses. Benefit means your disease is at least clinically and radiographically stable and you have not had any significant side effects. Your study doctor will continue to watch you for side effects and follow your condition for 30 days after your last dose of PD-0332991 (IBRANCE).
Clinical trial: NCT02255461
Section: Participant's Rights
Subsections: What Are My Rights If I Take Part In This Study?|What Are My Rights If I Take Part In This Study?|What Are My Rights If I Take Part In This Study?|What Are My Rights If I Take Part In This Study?

Taking part in the screening procedure is your choice. You may choose either to take part or not to take part in the screening procedure. No matter what decision you make, there will be no penalty to you and you will not lose any regular benefits. Your medical care will not be affected if you do not participate in this screening procedure. You can still get medical care from our institution. Who can answer my questions about the study? You can talk to the study doctor about any questions or concerns you have about this study.  
Contact the study doctor _*(insert name of study doctor[s])* at _*(insert telephone number).* For questions about your rights while in this study, call the _*(insert name of center)* Institutional Review Board (a group of people who review the research to protect your rights) at _____*(insert* telephone number).

Taking part in this study is your choice. No matter what your decision is, and even if your decision changes, there will be no penalty. You will not lose medical care or any legal rights. For questions about you rights while taking part in this study, call the *(institution name)* Institutional Review Board (a group of people who review the research to protect your rights) at (institution telephone number).

Taking part in the screening procedure is your choice. You may choose either to take part or not to take part in the screening procedure. No matter what decision you make, there will be no penalty to you and you will not lose any regular benefits. Your medical care will not be affected if you do not participate in this screening procedure. You can still get medical care from our institution. Who can answer my questions about the study? You can talk to the study doctor about any questions or concerns you have about this study.  
Contact the study doctor _*(insert name of study doctor[s])* at _*(insert telephone number).* For questions about your rights while in this study, call the _*(insert name of center)* Institutional Review Board (a group of people who review the research to protect your rights) at _____*(insert* telephone number).

Taking part in this study is your choice. No matter what your decision is, and even if your decision changes, there will be no penalty. You will not lose medical care or any legal rights. For questions about you rights while taking part in this study, call the *(institution name)* Institutional Review Board (a group of people who review the research to protect your rights) at (institution telephone number).
Clinical trial: NCT02255461
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Benefits Of Participating In This Study?|What Possible Risks Can I Expect From Taking Part In This **Study?**|What Are The Costs Of Taking Part In This Study?|What Happens If I Am Injured Because I Took Part In This Study?|What Are The Possible Risks?

There are no benefits from having this tissue testing done other than to show if you might be able to participate in the main research study.

If you choose to take part in this study, there is a risk that:
- You may lose time at work, school or home and spend more time in the hospital or doctor's office than usual
- You may be asked sensitive or private questions which you do not normally discuss The PD-0332991 (IBRANCE) used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. Your study doctor will be testing your blood and will address any changes that may affect your health. There is also a risk that you could have side effects from PD-0332991 (IBRANCE).  
Here are important points about side effects:
- Your study doctors do not know who will or will not have side effects.  
- Some side effects may go away soon, some may last a long time, or some may never go away.  
- Some side effects may interfere with your ability to have children.  
- Some side effects may be serious and may even result in death.  
Here are important points about how to make side effects less of a problem:
- Tell your study doctor if you notice or feel anything different so they can see if you are having a side effect.  
- Your study doctor may be able to treat some side effects.  
- Your study doctor may adjust the study drugs to try to reduce side effects.
Let your study doctor know of any questions you have about possible side effects. You can ask your study doctor questions about side effects at any time. The tables below show the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, your study doctor will discuss these with you.  
Side effects of PD-0332991 **(palbociclib; IBRANCE)**  
COMMON, SOME MAY BE SERIOUS  
In 100 people receiving palbociclib (PD-0332991), more than 20 and up to 100 may have:  
- Anemia which may require blood transfusion - Nausea  
- Tiredness - Infection, especially when white blood cell count is low  
| In 100 people receiving palbociclib (PD-0332991), more than 20 and up to 100 may have: - Anemia which may require blood transfusion - Nausea - Tiredness - Infection, especially when white blood cell count is low OCCASIONAL, SOME MAY BE SERIOUS  In 100 people receiving palbociclib (PD-0332991), from 4 to 20 may have:   |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| -   | Blurred vision, watering eyes                            |
|-----|----------------------------------------------------------|
| -   | Dry eye, skin                                            |
| -   | Constipation, diarrhea, vomiting                         |
| -   | Sores in the mouth which may cause difficulty swallowing |
| -   | Bruising, bleeding                                       |
| -   | Loss of appetite                                         |
| -   | Changes in taste                                         |
| -   | Headache                                                 |
| -   | Nose bleed                                               |
| -   | Hair loss, rash                                          |  
Reproductive risks: You should not get pregnant, breastfeed, or father a baby while in this study. The effects of PD-0332991 (IBRANCE) used in this study could be very damaging to an unborn baby. Women of childbearing potential must have a negative pregnancy test prior to study entry. Women of childbearing potential must agree to use an effective method of birth control during the study and for 97 days after completion of treatment. Check with your study doctor about what types of birth control, or pregnancy prevention, to use while in this study. In animal studies, male reproductive organ effects were seen when PD-0332991 (IBRANCE) was given to rats and dogs for at least 3 weeks. The effects include decay of seminiferous tubule structure (tubes in the testes where sperm is produced) and a decrease in semen fluid secretion (ability of semen to flow). These effects were reported minimal to severe depending on the dose given. These toxicities were seen at drug levels that are used in clinical research studies. However, reversal of these effects were seen either partially or completely, at least 4 weeks after PD-0332991(IBRANCE) is stopped. It is currently unknown what these findings mean for patients treated with palbociclib over time. If you are a male patient and want to have children at a later time, we recommend that you preserve your sperm prior to the study entry. Male patients must agree to use effective contraception during the study and for 97 days after completion of treatment. Routine studies in rats revealed that some of the animals developed cataracts (clouding of the eye lens) after being given PD-0332991 (IBRANCE) for 6 months. It is currently unknown what these findings mean for patients treated with PD-0332991 (IBRANCE) over time. You will have an eye examination done by your eye doctor to make sure that you do not have or are not developing cataracts before being registered on this study and every 3 months while on treatment. What possible benefits can I expect from taking part in this **study?** Taking part in this study may or may not make your health better. This study may help doctors learn more about how PD-0332991 (IBRANCE) affects your cancer. This information could help future cancer patients.

PD-0332991 (IBRANCE) will be supplied at no charge while taking part in this study. It is possible that PD-0332991 (IBRANCE) may not continue to be supplied while you are on the study. Although not likely, if this occurs, your study doctor will talk to you about other options. You or your health plan/insurance company will need to pay for all of the other costs of treating your cancer while in this study, including the cost of tests, procedures, or medicines to manage any side effects, unless your study doctor tells you certain tests are supplied at no charge. Before making a decision about participating in this study, you should check with your health plan or insurance company to find out exactly what they will pay for. You will not be paid for taking part in this study.

If you are injured or hurt as a result of taking part in this study and need medical treatment, please tell your study doctor. The study sponsor will not offer to pay for medical treatment for injury. Your insurance company may not be willing to pay for study-related injury. If you have no insurance, you would be responsible for any costs. If you feel this injury was a result of medical error, you keep all your legal rights to receive payment for this even though you are in a study.

1. The most common risks related to drawing blood from your arm are brief pain and possibly a bruise.  
2. There is a risk that someone could get access to the personal information in your medical records or other information researchers have stored.  
3. There is a risk that someone could trace the information in a central database back to you.  
Even without your name or other identifiers, your genetic information is unique. The researchers believe the chance that someone will identify you is very small, but the risk may change in the future as people come up with new ways of tracing information.  
4. There can also be a risk in knowing genetic information. New health information about inherited traits that might affect you or blood relatives could be found during a study. The researchers believe the chance these things will happen is very small, but cannot promise that they will not occur. In general, we will not give you any individual results from the study of the samples you gave us. This is because it will probably be a long time before we will know how to interpret the information accurately. In the rare instance that one of the genes tested might turn out to be an important risk factor for a disease, and having that information could allow you to take steps to prevent, detect earlier, or better treat that disease, we will ask you whether you want to know those results. If so, we will contact you and your doctor to discuss more testing.  
5. Some of your genetic and health information may be placed in central databases that may be public, along with information from many other people. The data resulting from the genetic research may be deposited into a public or controlled access database made available to other researchers. Information that could directly identify you will not be included. However, people may develop ways in the future that would allow someone to link your genetic or medical information in our databases back to you. For example, someone could compare information in our databases with information from you (or a blood relative) in another database and be able to identify you (or your blood relative). It also is possible that there could be violations to the security of the computer systems used to store the codes linking your genetic and medical information to you.  
How will information be kept private? Your privacy is very important to the researchers and they will make every effort to protect it. Here are just a few of the steps they will take:
1. When your sample(s) is sent to the researchers, no information identifying you (such as your name) will be sent. Samples will be identified by a unique code only.  
2. The list that links the unique code to your name will be kept separate from your sample and health information.  
3. Information that identifies you will not be given to anyone, unless required by law. 4. If research results are published, your name and other personal information will not be used.  
What are the possible benefits? You will not benefit from taking part. The researchers, using the samples from you and others, might make discoveries that could help people in the future. What if I change my mind? If you decide you no longer want research samples to be used, you can contact your study doctor in writing, *(insert name of study doctor)* who will let the researchers know. Then, any sample that remains in the bank will no longer be used and related health information will no longer be collected. Samples or related information that have already been given to or used by researchers will not be returned. If data has been submitted to a data repository, please include in your letter a request to retrieve your data. What if I have more questions? If you have questions about the use of your samples for research, contact the study doctor, [Physician's name] at [Physician's telephone number]. For each of the optional studies below, please circle your response and then initial and date on the line provided.
Clinical trial: NCT02255461
Section: Procedures
Subsections: What Is Involved In This Screening Procedure?|What Extra Tests And Procedures Will I Have If I Take Part In This Study?|- Screening For Rb1 Protein|- Electrocardiogram (Ekg)|What Will Happen If I Take Part In This Research Study?

If you agree to have this screening test done, the study team will collect your date of birth to confirm your age, your tumor diagnosis, your height and weight and availability of your tumor tissue that was collected during a previous surgery. The screening procedure will also include sending a piece of tumor tissue that was collected during a surgery to a laboratory at University of California, San Francisco (UCSF). Investigators from UCSF will look for the presence of Rb1 protein in the tumor tissue. If Rb1 protein is present, the study doctor or study nurse will discuss the main research study with you and you will be able to ask questions. If you are interested in taking part in the research study, you will be scheduled to have the rest of the eligibility procedures performed. You must meet all other eligibility criteria before you will able to participate in the main research study.

Most of the exams, tests, and procedures you will have are part of routine medical care for this type of cancer. However, there are some extra exams, tests and/or procedures that will need to be completed if you take part in this study.

If you have any type of CNS tumors other than DIPG, medulloblastoma, or ATRT, you will be asked to participate in the screening portion of this study. A screening test for presence or absence of Rb1 will be performed at a laboratory at University of California (UCSF). Your study doctor will send glass slides containing tumor tissue that was collected from a previous surgery to the lab. The tumor tissue will be stained to identify the Rb1 protein. Based on this analysis, which will take about 14 days, we will learn whether or not you are eligible for the study.

An electrocardiogram is a simple, painless test that records the heart's electrical activity. To assess the activity of your heart, your study doctor will do an EKG before you start the treatment. An EKG will also be performed 3 hours after you take the study drug PD-0332991 (IBRANCE) on days 1, 8 and 15 of Course 1. An EKG will also be done at these time points: day 1 of Courses 2 and 3, every 12 weeks and again at the end of treatment.  
- Eye exam An eye exam will be performed by an ophthalmologist to make sure that you do not have or are not developing cataracts. It will be performed before you start the treatment and every 3 months while on study.  
- Pharmacokinetics (PK) blood (required)
You are required to take part in this study because determining how the body handles this drug is an important part of the study. Your study doctor would like to learn how much PD-0332991 (IBRANCE) stays in the blood for specific time points after the drug is taken. A total of about 2 tablespoons (32 milliliters) of blood will be collected during the study. Blood samples will be collected from you to determine how much of the drug stays in the blood. Less than ½ teaspoon (about 2 mL) of blood will be collected each time from your arm or central line before you start treatment and 30 minutes, 1, 2, 4, 8, 10 (optional), 24 and 48 hours after your first dose of PD-0332991 (IBRANCE). You will be told NOT to take PD-0332991
(IBRANCE) on Day 2 to collect the blood samples at 24 and 48 hour. Then, the same amount of blood will also be collected on Day 21 of Course 1 before you take PD-0332991 (IBRANCE) and 1, 2, 4, 8, 10 (optional) and 24 hours after you take PD-0332991 (IBRANCE). The risks are the same for any blood sample collected from your line. If you don't have a central line, the most common risks related to drawing blood from your arm are brief pain and possibly a bruise. Your privacy is very important to the researchers and they will make every effort to protect it. Your samples are sent to the research doctor but no information identifying you (such as your name or medical record number) will be sent. Samples will be identified by a unique code only. Information that identifies you will not be given to anyone, unless required by law. If research results are published, your name and other personal information will not be used. You will not be billed for this required special study (Pharmacokinetics).  
- PK blood after stopping Dexamethasone (steroid treatment given to decrease swelling in your brain) (optional)
This test is optional. The study doctor would like to find out how much PD-0332991 (IBRANCE) stays in the blood after you stop taking dexamethasone. If you choose to take part and have received dexamethasone during the required PK studies, the study doctor will collect serial blood samples at least 2 weeks after stopping dexamethasone, and after 2 weeks of continuous treatment with PD-0332991 (IBRANCE). Less than ½ teaspoon (about 2 mL) of blood will be collected for each sample.  
- Pharmacogenetics (optional)
If you choose to take part, a blood sample will be collected from you to determine if there are changes of certain genes that control how PD-0332991 (IBRANCE) is metabolized in the body. This test will require about 1 teaspoon (5 mL) of blood to be collected from your central line or a vein in your arm before you start the treatment.  
- Pre-trial tumor material for genomics (optional)
Genomic research is research that studies the genes and their functions. Your blood and tumor cells contain genes, which are made up of DNA and which serve as the "instruction book" for cellular function. If you choose to take part, your study doctor would like to send a small piece of tumor material that is available from a previous surgery. The researchers will look for biological markers to help them understand the tumor better and how it might respond to the study drug.

A study plan below shows how often these tests and procedures will be done while you are on this research study. 28 June *2018* Study Plan  
| Completion/                                                                                                                                                            |                         |                                                           |                      |    |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|-----------------------------------------------------------|----------------------|----|
| Discontinuation Of Treatment                                                                                                                                           |                         |                                                           |                      |    |
| PHYSICAL ASSESSMENTS Medical history, physical exam, vital signs,  performance status, neurological exam                                                               | X                       | Every week                                                | Every month          | X  |
| Blood counts                                                                                                                                                           | X                       | Every week                                                | Every week           | X  |
| Blood Chemistries                                                                                                                                                      | X                       | Every week                                                | Every month          | X  |
| Blood pregnancy test (for females who might  be able to have children)                                                                                                 | X                       | Before each course                                        |                      |    |
| Pre                                                                                                                                                                        |                         |                                                           |                      |    |
| therapy                                                                                                                                                                | Course 1                | Course 2 - Course  26                                     |                      |    |
| Test /Procedure Spinal tap (if needed)                                                                                                                                 | X                       | Day 1 of Course 2,                                        |                      |    |
| EKG                                                                                                                                                                    | X                       | Day 1, 8, 15                                              | 3, 6, 9, 12, 15, 18, | X  |
| 21 and 24                                                                                                                                                              |                         |                                                           |                      |    |
| Eye exam                                                                                                                                                               | X                       | Course 3, 6, 9, 12,  15, 18, 21 and 24 Course 2, 4, 6 and |                      |    |
| Brain scan                                                                                                                                                             | X                       | then every 12                                             | X                    |    |
| weeks                                                                                                                                                                  |                         |                                                           |                      |    |
| Spine scan (if needed)                                                                                                                                                 | X                       | Same as Brain MRI  if needed                              | X                    |    |
| Take PD-0332991 (IBRANCE) once a day;  record in the pill diary                                                                                                        | X                       | X                                                         |                      |    |
| Optional research tests Screening Pre-trial tumor materials for Rb1  testing (required for patients with all types of  CNS tumors except DIPG, medulloblastoma,  ATRT) | X                       |                                                           |                      |    |
| Pharmacogenetics (if consented)                                                                                                                                        | X                       |                                                           |                      |    |
| Pharmacokinetics blood (required)                                                                                                                                      | X                       | Day 1, 2, 3,  21 and 22                                   |                      |    |
| PK blood after discontinuation of                                                                                                                                      | Any time after stopping |                                                           |                      |    |
| dexamethasone (if consented)                                                                                                                                           | dexamethasone           |                                                           |                      |    |
| Pre-trial tumor materials for Genomics (if  consented)                                                                                                                 | X                       |                                                           |                      |    |
| Tumor Tissue and blood for Biorepository (if  consented)                                                                                                               | X                       |                                                           |                      |    |
Clinical trial: NCT02255461
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Why Is This Study Being Done?|Why Is This Study Being Done?|Why Is This Study Being Done?

The purpose of this study is to perform a test on a sample of your tumor which was removed at the time of your surgery and has been stored in a hospital laboratory. This screening procedure is a test to see if you might qualify to take part in a main research study using a study drug called PD-0332991 (IBRANCE). By signing this consent form, you are not agreeing to participate in the main research study, but only agreeing to have this test done. In order to participate in the main research study, your study doctor must assess whether your tumor tissue has a specific protein called Rb1 protein. This Rb1 protein is a protein that suppresses tumor growth. In certain tumors, cancer cells inactivate Rb1 protein so that it can no longer act as a tumor suppressor. However, over 60 percent of brain tumors in children still have Rb1 protein present and we want to find out whether your tumor has Rb1 protein or not. PD0332991 (IBRANCE) is a capsule that prevents the inactivation of Rb1, thereby suppressing tumor growth. You are being asked to participate in this study because you have a type of brain tumor other than diffuse pontine glioma (DIPG), medulloblastoma, or Atypical Teratoid Rhabdoid Tumor (ATRT) which has grown or come back after the usual treatment. Up to 55 people will be screened throughout the United States.  
1

Tumor cells grow and divide rapidly and uncontrollably. In normal cells, specific proteins called cyclin dependent kinases (CDK4 and 6) tightly control the process of cell division. Another protein called Rb1 also regulates cell division and stops the cells from dividing. By stopping cell division, the Rb1 protein suppresses tumor formation in normal cells. But in cancer, CDK4 and 6 are out of control and drive the cell to divide and form cancer. Tumor cells can sometimes inactivate Rb1 to help them divide continuously. In this study, we are testing a study drug called PD-0332991 (IBRANCE) that works by inhibiting the CDK4 and 6 proteins. In animal studies, researchers have found that this drug works only if tumor cells have an intact Rb1 protein. Over 60 percent of brain tumors in children are likely to have an intact Rb1 protein. You have been approached for this study because your tumor has been identified to have an intact Rb1 protein. This drug is not FDA approved to treat brain tumors and is considered experimental. PD-0332991 (IBRANCE) has been previously tested in adults only. This study is the first time this drug is being given to children. Therefore we are testing different doses of the drug to determine the maximum dose that can be safely given to children with cancer. Our hope is that PD-0332991 (IBRANCE) will be a more effective treatment for many types of childhood brain tumors. Approximately 42 - 50 people are expected to take part in this study throughout the United States. About 55 people will be screened in order to achieve this goal. The purposes of this study are:
1. To find the highest dose of PD-0332991 (IBRANCE) that can be given without causing severe side effects in two study groups.  
2. To learn what side effects may occur when PD-0332991 (IBRANCE) is given. 3. To learn how the body handles PD-0332991 (IBRANCE) by studying the levels of the drug in the blood.

The purpose of this study is to perform a test on a sample of your tumor which was removed at the time of your surgery and has been stored in a hospital laboratory. This screening procedure is a test to see if you might qualify to take part in a main research study using a study drug called PD-0332991 (IBRANCE). By signing this consent form, you are not agreeing to participate in the main research study, but only agreeing to have this test done. In order to participate in the main research study, your study doctor must assess whether your tumor tissue has a specific protein called Rb1 protein. This Rb1 protein is a protein that suppresses tumor growth. In certain tumors, cancer cells inactivate Rb1 protein so that it can no longer act as a tumor suppressor. However, over 60 percent of brain tumors in children still have Rb1 protein present and we want to find out whether your tumor has Rb1 protein or not. PD0332991 (IBRANCE) is a capsule that prevents the inactivation of Rb1, thereby suppressing tumor growth. You are being asked to participate in this study because you have a type of brain tumor other than diffuse pontine glioma (DIPG), medulloblastoma, or Atypical Teratoid Rhabdoid Tumor (ATRT) which has grown or come back after the usual treatment. Up to 55 people will be screened throughout the United States.  
1

Tumor cells grow and divide rapidly and uncontrollably. In normal cells, specific proteins called cyclin dependent kinases (CDK4 and 6) tightly control the process of cell division. Another protein called Rb1 also regulates cell division and stops the cells from dividing. By stopping cell division, the Rb1 protein suppresses tumor formation in normal cells. But in cancer, CDK4 and 6 are out of control and drive the cell to divide and form cancer. Tumor cells can sometimes inactivate Rb1 to help them divide continuously. In this study, we are testing a study drug called PD-0332991 (IBRANCE) that works by inhibiting the CDK4 and 6 proteins. In animal studies, researchers have found that this drug works only if tumor cells have an intact Rb1 protein. Over 60 percent of brain tumors in children are likely to have an intact Rb1 protein. You have been approached for this study because your tumor has been identified to have an intact Rb1 protein. This drug is not FDA approved to treat brain tumors and is considered experimental. PD-0332991 (IBRANCE) has been previously tested in adults only. This study is the first time this drug is being given to children. Therefore we are testing different doses of the drug to determine the maximum dose that can be safely given to children with cancer. Our hope is that PD-0332991 (IBRANCE) will be a more effective treatment for many types of childhood brain tumors. Approximately 42 - 50 people are expected to take part in this study throughout the United States. About 55 people will be screened in order to achieve this goal. The purposes of this study are:
1. To find the highest dose of PD-0332991 (IBRANCE) that can be given without causing severe side effects in two study groups.  
2. To learn what side effects may occur when PD-0332991 (IBRANCE) is given. 3. To learn how the body handles PD-0332991 (IBRANCE) by studying the levels of the drug in the blood.
Clinical trial: NCT02255461
Section: Voluntary Participation
Subsections: Will I Be Paid If I **Take Part In This Screening Procedure?**

Participation in this screening procedure is voluntary. No payment for participation will be given. What happens if I am injured because I took part in this study? There is no risk of injury involved because this screening test will use previously collected tumor sample material.
Clinical trial: NCT02255461
Section: Withdrawal from Study
Subsections: Can I Stop Taking Part In This **Study?**

Yes. You can decide to stop at any time. If you decide to stop for any reason, it is important to let your study doctor know as soon as possible so you can stop safely. If you stop, you can decide whether or not to let your study doctor continue to provide medical information to the organization running the study. Your study doctor will provide any new information or changes in the study that may affect your health or willingness to continue in the study.  
The doctor may decide to take you out of the study:
- If the side effects are too harmful to you
- If you need a treatment not allowed on this study - If your tumor returns or grows
- If you do not follow the study rules
- If new information becomes available - If the study is stopped by the sponsor, IRB or FDA