Clinical trial: NCT03387020
Section: Alternatives
Subsections: What Other Choices Do I Have If I Do Not Take Part In This Study?|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

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: NCT03387020
Section: Confidentiality
Subsections: Who Will Know About My Participation In This Screening Study?|How Will Information Be Kept Private?|Who Will See My Medical Information?|Who Will See My Medical Information?|Who Will See My Medical Information?|Who Will See My Medical Information?

Your privacy is very important to us. The study doctors will make every effort to protect it. The study doctors have a privacy permit to help protect your records if there is a court case. However, some of your medical information may be given out if required by law. If this should happen, the study doctors will do their best to make sure that any information that goes out to others will not identify who you are. Some of your health information, such as your response to cancer treatment, results of study tests, and medicines you took, will be kept by the study sponsor in a central research database. However, your name and contact information will not be put in the database. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used. There are organizations that may look at your study records. Your health information in the research database also may be shared with these organizations. They must keep your information private, unless required by law to give it to another group. Some of these organizations are:
- Your referring physician.  
- The Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who take part in the study
- 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
- Novartis and its authorized agents 3 NCI Protocol \#: PBTC-050 Version Date: September 4, 2018 Updated Date: September 26, 2018  
- Governmental agencies in other countries where the study drug may be considered for approval
- Cincinnati Children's Hospital Medical Center
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 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. Researchers to whom the Pediatric Brain Tumor Consortium (PBTC) sends your sample and information will not know who you are. They must also sign an agreement that they will not try to find out who you are.  
4. Information that identifies you will not be given to anyone, unless required by law. 5. 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. Are there any costs or payments? There are no costs to you or your insurance. You will not be paid for taking part. If any of the research leads to new tests, drugs, or other commercial products, you will not share in any profits.

Your privacy is very important to us. The study doctors will make every effort to protect it. The study doctors have a privacy permit to help protect your records if there is a court case. However, some of your medical information may be given out if required by law. If this should Updated Date: September 26, 2018 happen, the study doctors will do their best to make sure that any information that goes out to others will not identify who you are. Some of your health information, such as your response to cancer treatment, results of study tests, and medicines you took, will be kept by the study sponsor in a central research database. However, your name and contact information will not be put in the database. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used. There are organizations that may look at and/or receive copies of your records. These organizations are required to make sure your information is kept private, unless required by law to provide information to another group. Some of these organizations are:
The Pediatric Brain Tumor Consortium (PBTC), who coordinate this study Laboratories performing the required and optional research studies of tumor, blood and CSF samples The Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who take part in the study.  
Federal agencies such as the Food and Drug Administration, the Office of Human Research Protections (OHRP) and the National Cancer Institute in the U.S.  
Governmental agencies in other countries where the study drug may be considered for approval.  
The pharmaceutical company, Novartis that supplies ribociclib and its authorized agents.  
Your insurance company or other health benefits plan (if charges are billed to these plans).  
The PBTC will make every effort to keep your name and identifying information confidential. 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.

Your privacy is very important to us. The study doctors will make every effort to protect it. The study doctors have a privacy permit to help protect your records if there is a court case. However, some of your medical information may be given out if required by law. If this should happen, the study doctors will do their best to make sure that any information that goes out to others will not identify who you are. Some of your health information, such as your response to cancer treatment, results of study tests, and medicines you took, will be kept by the study sponsor in a central research database. However, your name and contact information will not be put in the database. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used.  
There are organizations that may look at your study records. Your health information in the research database also may be shared with these organizations. They must keep your information private, unless required by law to give it to another group.  
Some of these organizations are:
The Pediatric Brain Tumor Consortium, who coordinate this study Laboratories performing the required and optional research studies of tumor, blood and CSF samples The Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who take part in the study.  
Federal agencies such as the Food and Drug Administration, the Office of Human Research Protections (OHRP) and the National Cancer Institute in the U.S.  
Governmental agencies in other countries where the study drug may be considered for approval
Updated Date: September 26, 2018  
The pharmaceutical company, Novartis that supplies ribociclib and everolimus and its authorized agents.  
Your insurance company or other health benefits plan (if charges are billed to these plans).
The PBTC will make every effort to keep your name and identifying information confidential. 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.

Your privacy is very important to us. The study doctors will make every effort to protect it. The study doctors have a privacy permit to help protect your records if there is a court case. However, some of your medical information may be given out if required by law. If this should Updated Date: September 26, 2018 happen, the study doctors will do their best to make sure that any information that goes out to others will not identify who you are. Some of your health information, such as your response to cancer treatment, results of study tests, and medicines you took, will be kept by the study sponsor in a central research database. However, your name and contact information will not be put in the database. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used. There are organizations that may look at and/or receive copies of your records. These organizations are required to make sure your information is kept private, unless required by law to provide information to another group. Some of these organizations are:
The Pediatric Brain Tumor Consortium (PBTC), who coordinate this study Laboratories performing the required and optional research studies of tumor, blood and CSF samples The Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who take part in the study.  
Federal agencies such as the Food and Drug Administration, the Office of Human Research Protections (OHRP) and the National Cancer Institute in the U.S.  
Governmental agencies in other countries where the study drug may be considered for approval.  
The pharmaceutical company, Novartis that supplies ribociclib and its authorized agents.  
Your insurance company or other health benefits plan (if charges are billed to these plans).  
The PBTC will make every effort to keep your name and identifying information confidential. 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.

Your privacy is very important to us. The study doctors will make every effort to protect it. The study doctors have a privacy permit to help protect your records if there is a court case. However, some of your medical information may be given out if required by law. If this should happen, the study doctors will do their best to make sure that any information that goes out to others will not identify who you are. Some of your health information, such as your response to cancer treatment, results of study tests, and medicines you took, will be kept by the study sponsor in a central research database. However, your name and contact information will not be put in the database. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used.  
There are organizations that may look at your study records. Your health information in the research database also may be shared with these organizations. They must keep your information private, unless required by law to give it to another group.  
Some of these organizations are:
The Pediatric Brain Tumor Consortium, who coordinate this study Laboratories performing the required and optional research studies of tumor, blood and CSF samples The Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who take part in the study.  
Federal agencies such as the Food and Drug Administration, the Office of Human Research Protections (OHRP) and the National Cancer Institute in the U.S.  
Governmental agencies in other countries where the study drug may be considered for approval
Updated Date: September 26, 2018  
The pharmaceutical company, Novartis that supplies ribociclib and everolimus and its authorized agents.  
Your insurance company or other health benefits plan (if charges are billed to these plans).
The PBTC will make every effort to keep your name and identifying information confidential. 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: NCT03387020
Section: Duration of Study Involvement
Subsections: How Long Will I Be In The Study?|How Long Will I Be In This Study?|How Long Will I Be In This Study?|How Long Will I Be In This 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. After the screening procedure is completed: If you are eligible and interested in taking part of the surgical study, this portion will take about 2 months. After you complete the surgical study portion, you will also be given an option of joining the Phase I portion. The Phase I portion will take 1 to 2 years. You will receive ribociclib and everolimus for approximately 1 year (13 courses) and if there are no side effects, you may continue the study for another year (total 2 years).

You will receive the ribociclib for 7 to 10 days prior to the resection of your brain tumor tissue. During and after tumor resection, your study doctor will watch you for any significant side effects. The study doctor will continue to watch you and follow your condition until you are completely recovered from the surgery. It is expected that this surgical study will take you about 2 months to finish. You will then return to your doctor for re-evaluation and your doctor will also discuss with you for an option of switching over to Phase I study. You will be given a copy of the Phase I consent which covers more details about that study. If you are interested in taking part, talk to your doctor.

You will receive the study drugs, ribociclib and everolimus for 13 courses (approximately 1 year). If you have benefited from receiving ribociclib and everolimus, and the study doctor agrees, you may be able to continue taking ribociclib and everolimus for another year (for a total 26 courses). Benefit means your disease is at least clinically and radiographically stable and you have not had any significant side effects. If you stop taking the study drugs due to side effects from ribociclib and/or everolimus, the study doctor will follow you weekly for the first 4 weeks and then every 4weeks until these side effects are resolved. When you finish therapy for 2 years, the study doctor will continue to watch you for side effects and follow your condition for 30 days after your last doses of ribociclib and everolimus. If the side effects that are continuing at the end of day 30, the study doctor may still follow you until they are resolved or until you start another cancer therapy or until your tumor grows. Follow up can be done by clinic visits and/or updates over the phone as determined by your study doctor.

You will receive the ribociclib for 7 to 10 days prior to the resection of your brain tumor tissue. During and after tumor resection, your study doctor will watch you for any significant side effects. The study doctor will continue to watch you and follow your condition until you are completely recovered from the surgery. It is expected that this surgical study will take you about 2 months to finish. You will then return to your doctor for re-evaluation and your doctor will also discuss with you for an option of switching over to Phase I study. You will be given a copy of the Phase I consent which covers more details about that study. If you are interested in taking part, talk to your doctor.

You will receive the study drugs, ribociclib and everolimus for 13 courses (approximately 1 year). If you have benefited from receiving ribociclib and everolimus, and the study doctor agrees, you may be able to continue taking ribociclib and everolimus for another year (for a total 26 courses). Benefit means your disease is at least clinically and radiographically stable and you have not had any significant side effects. If you stop taking the study drugs due to side effects from ribociclib and/or everolimus, the study doctor will follow you weekly for the first 4 weeks and then every 4weeks until these side effects are resolved. When you finish therapy for 2 years, the study doctor will continue to watch you for side effects and follow your condition for 30 days after your last doses of ribociclib and everolimus. If the side effects that are continuing at the end of day 30, the study doctor may still follow you until they are resolved or until you start another cancer therapy or until your tumor grows. Follow up can be done by clinic visits and/or updates over the phone as determined by your study doctor.
Clinical trial: NCT03387020
Section: Participant's Rights
Subsections: 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).  
Where can I get more information?  
You may call the National Cancer Institute's Cancer Information Service at: 1-800-4-CANCER (1-800-422-6237) You may also visit the NCI Web site at http://cancer.gov/ For NCI's clinical trials information, go to: http://cancer.gov/clinicaltrials/. For NCI's general information about cancer, go to http://cancer.gov/cancerinfo/ You will get a copy of this form. If you want more information about this study, ask your study doctor.  
4
Clinical trial: NCT03387020
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Benefits Of Participating In This Study?|What Are The Possible Risks?|What Possible Risks Can I Expect From Taking Part In This Study?|What Possible Benefits Can I Expect From Taking Part In This Study?|What Possible Risks Can I Expect From Taking Part In This Study? If You Choose To Take Part In This Study, There Is A Risk That:|Side Effects Of Ribociclib Very Common, Some May Be Serious In 10 People Receiving Ribociclib, More Than 1 May Have:|Side Effects Of Everolimus Common, Some May Be Serious

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.

1. There is a risk that someone could get access to the personal information in your medical records or other information researchers have stored.  
2. 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.  
3. 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.  
4. 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 5 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.

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 study drug, ribociclib used in this study may affect how different parts of your body work such as the 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 the study drug, ribociclib.  
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.
Updated Date: September 26, 2018 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 ribociclib  
VERY COMMON, SOME MAY BE SERIOUS  
In 10 people receiving ribociclib, more than 1 may have:  
Low number of red blood cells that can causes tiredness and shortness of breath. May  
require a blood transfusion  
Fever  
Low white blood cell counts which may lead to infection  
Constipation  
Diarrhea  
Sores in mouth which may cause difficulty swallowing  
Nausea  
Vomiting  
Tiredness Decreased appetite Swelling (arm/leg)  
Change in the heart rhythm  
Kidney infection  
Back pain  
Headache  
Difficulty sleeping  
Shortness of breath  
Rash  
Itching Hair loss Abdominal pain  
COMMON, SOME MAY BE SERIOUS  
In 100 people receiving ribociclib, more than 1 may have:  
Low white blood cell count with fever Low platelet count which may cause bleeding and bruising Fainting episode Dry eyes Tears increased  
Taste changes which may affect the way foods normally taste  
Heartburn Liver injury which may cause yellowing of eyes and skin or swelling Low blood salts that may cause muscle cramping Nose bleed  
Reddening of the skin  
Weight loss  
Changes in heart rhythms that may cause dizziness or heart palpitations  
Let your study doctor know of any questions you have about possible side effects. You can ask the study doctor questions about side effects at any time.  
Reproductive risks: You should not get pregnant, breastfeed, or father a baby while in this study. The effects of ribociclib used in this study could be very damaging to an unborn baby. If you are of childbearing or child fathering potential, you must agree to use at least one of the following methods of birth control during the study and for 8 weeks following the last dose of ribociclib.  
Be sexually inactive (total abstinence)
Combination of any of the two following methods 1. Use of hormonal methods (contraceptive pills, injection, implant, vaginal ring, transdermal)
2. Have an Intrauterine device in place 3. Barrier methods: Condom or Occlusive cap (diaphragm or cervical/vault caps)
with spermicidal foam/gel/film/cream/ vaginal suppository Check with your study doctor about what types of birth control, or pregnancy prevention, to use while in this study. If you or your partner becomes pregnant while participating in this study, please notify your study doctor immediately and if you are a female, you will not be able to continue in the study.

Taking part in this study may or may not make your health better. While researchers hope that once a day ribociclib for 7 to 10 days before removal of brain tumor tissue will be more useful against the usual treatment when compared (surgical removal of the brain tumor with or without ribociclib), there is no proof of this yet. We do know that the information from this study may help us learn more about the use of ribociclib and brain surgery as a treatment for brain tumor. This information may help people in the future.

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 study drugs, ribociclib and everolimus used in this study may affect how different parts of your body work such as the 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 the study drugs, ribociclib and/or everolimus. Here are important points about side effects: Updated Date: September 26, 2018 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.  
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.

Low number of red blood cells that can causes tiredness and shortness of breath. May require a blood transfusion Fever Low white blood cell counts which may lead to infection Constipation Diarrhea Sores in mouth which may cause difficulty swallowing Nausea Vomiting Tiredness Decreased appetite Swelling (arm/leg)
Change in the heart rhythm Kidney infection Back pain Headache Difficulty sleeping Shortness of breath Rash Itching Hair loss Abdominal pain COMMON, SOME MAY BE SERIOUS
In 100 people receiving ribociclib, more than 1 may have: Updated Date: September 26, 2018 Low white blood cell count with fever Low platelet count which may cause bleeding and bruising Fainting episode Dry eyes Watering eyes Taste changes which may affect the way foods normally taste Heartburn Liver injury which may cause yellowing of eyes and skin or swelling Low blood salts that may cause muscle cramping Nose bleed Reddening of the skin Weight Loss Changes in the heart rhythm that may cause dizziness or heart palpitations

In 100 people receiving everolimus (RAD-001), more than 20 and up to 100 may have:
Anemia which may require blood transfusion Diarrhea Sores in the mouth which may cause difficulty swallowing Tiredness Rash Swelling of arms or legs Nausea, vomiting Weight loss, loss of appetite Infections, especially when white blood cell count is low Headache Changes in taste Nose bleed Damage to the lungs which may cause shortness of breath Rash Itching Cough OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving everolimus (RAD-001), from 4 to 20 may have: Updated Date: September 26, 2018  
Pain  
  
  
  
Constipation, Heartburn Dry mouth Fever Bruising, bleeding Shortness of breath  
  
  
Let your study doctor know of any questions you have about possible side effects. You can ask the study doctor questions about side effects at any time.  
Reproductive risks: You should not get pregnant, breastfeed, or father a baby while in this study.  
The effects of ribociclib and everolimus used in this study could be very damaging to an unborn baby. If you are of childbearing or child fathering potential, you must agree to use at least one of the following methods of birth control during the study and for 8 weeks following the last dose of ribociclib and everolimus.  
Be sexually inactive (total abstinence)
Combination of any of the two following methods 1. Use of hormonal methods (contraceptive pills, injection, implant, vaginal ring, transdermal)
2. Have an Intrauterine device in place 3. Barrier methods: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository Check with your study doctor about what types of birth control, or pregnancy prevention, to use while in this study. If you or your partner becomes pregnant while participating in this study, please notify your study doctor immediately and if you are a female, you will not be able to continue in the study. What possible benefits can I expect from taking part in this study? This study is unlikely to help you. We do know that the information from this study may help us learn more about the use of ribociclib and everolimus when given in combination for treatment in brain tumor. This information may help people in the future.  
|    | Non-healing surgical site                                                                                                  |
|-----|----------------------------------------------------------------------------------------------------------------------------|
|    | Kidney damage which may require dialysis                                                                                   |
|    | Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of  breath, swelling of the face or throat |  
  
  
Updated Date: September 26, 2018
Clinical trial: NCT03387020
Section: Procedures
Subsections: What Is Involved In This Screening Procedure?|What Is Involved?|What Extra Tests And Procedures Will I Have If I Take Part In This Study?|What Extra Tests And Procedures Will I Have If I Take Part In This Study?|What Extra Tests And Procedures Will I Have If I Take Part In This Study?|What Extra Tests And Procedures Will I Have If I Take Part In This Study?

This screening procedure will include sending a piece of tumor tissue collected from a previous surgery to a laboratory at Cincinnati Children's Hospital Medical Center. However, if this test was completed at your local institution in a CLIA certified laboratory, we will be able to review those results to determine if additional testing is needed to confirm Rb1 status. The Investigators will look for the presence of Rb1 protein in the tumor tissue. Results from this test will determine if you are eligible to take part in the main research study. 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 are able to participate in the main research study.

1. Your leftover tumor samples after the screening test is completed at CCHMC will be sent to the PBTC Central Review and Biorepository (PBTC CRB).  
2. Your samples and some related health information may be stored in the PBTC Central Review and Biorepository (PBTC CRB), along with samples and information from other people who take part. The samples will be kept until they are used up. Information from your medical record will be updated from time to time.  
3. Qualified researchers can submit a request to use the materials stored in the Repository.  
The science committee of the PBTC and/or the National Cancer Institute, will review each request. Researchers will not be given your name or any other information that could directly identify you.  
4. Neither you nor your study doctor will be notified when research will be conducted or given reports or other information about any research that is done using your samples.  
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. Information that could directly identify you will not be included.

Most of the exams, tests, and procedures you will have are part of routine medical care for this type of cancer and may be done even if you do not join the study. On some days when you have labs, your doctor may tell you that you can't have anything to eat or drink before your labs are drawn. However, there are some extra tests and/or procedures that will need to be completed if you take part in this study. They are considered research related procedures and not part of the usual approach for this type of cancer.

Most of the exams, tests, and procedures you will have are part of routine medical care for this type of cancer and may be done even if you do not join the study. On some days when you have labs, your doctor may tell you that you can't have anything to eat or drink before your labs are drawn. However, there are some extra tests and/or procedures that will need to be completed if Updated Date: September 26, 2018 you take part in this study. They are considered research related procedures and not part of the usual approach for this type of cancer.  
Before you begin the study:
You will need to have the following extra tests and procedures to find out if you can be in the study:
Screening for Rb1 protein This study has a screening step. Because you have a type of brain tumor that is either High Grade Glioma or medulloblastoma or CNS embryonal tumor (NOS) or Ependymoma, or ATRT or atypical DIPG which has biopsied, this screening test was performed on your tumor tissue that was collected from a previous surgery and the test result showed that your tumor has an intact Rb1 protein. Based on this result, we know that you are eligible to see if you meet all of the other requirements for the Phase 1 part of this study.  
Electrocardiogram (EKG)
An electrocardiogram is a simple, painless test that records the heart's electrical activity.  
ECHO
An echocardiogram uses sound waves to make pictures of your heart, which helps to show how well your heart pumps blood.  
If the exams, tests, and procedures show that you can take part in the study, and you choose to take part, then you will need the extra tests and procedures listed in the Study Calendar. They are not part of the usual approach for your type of cancer.

Most of the exams, tests, and procedures you will have are part of routine medical care for this type of cancer and may be done even if you do not join the study. On some days when you have labs, your doctor may tell you that you can't have anything to eat or drink before your labs are drawn. However, there are some extra tests and/or procedures that will need to be completed if you take part in this study. They are considered research related procedures and not part of the usual approach for this type of cancer.

Most of the exams, tests, and procedures you will have are part of routine medical care for this type of cancer and may be done even if you do not join the study. On some days when you have labs, your doctor may tell you that you can't have anything to eat or drink before your labs are drawn. However, there are some extra tests and/or procedures that will need to be completed if Updated Date: September 26, 2018 you take part in this study. They are considered research related procedures and not part of the usual approach for this type of cancer.  
Before you begin the study:
You will need to have the following extra tests and procedures to find out if you can be in the study:
Screening for Rb1 protein This study has a screening step. Because you have a type of brain tumor that is either High Grade Glioma or medulloblastoma or CNS embryonal tumor (NOS) or Ependymoma, or ATRT or atypical DIPG which has biopsied, this screening test was performed on your tumor tissue that was collected from a previous surgery and the test result showed that your tumor has an intact Rb1 protein. Based on this result, we know that you are eligible to see if you meet all of the other requirements for the Phase 1 part of this study.  
Electrocardiogram (EKG)
An electrocardiogram is a simple, painless test that records the heart's electrical activity.  
ECHO
An echocardiogram uses sound waves to make pictures of your heart, which helps to show how well your heart pumps blood.  
If the exams, tests, and procedures show that you can take part in the study, and you choose to take part, then you will need the extra tests and procedures listed in the Study Calendar. They are not part of the usual approach for your type of cancer.
Clinical trial: NCT03387020
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?|Why Is This Study Being Done?|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 Goals Of This Study Are:

The purpose of this screening consent is to perform a test on a sample of your tumor tissue which was removed at the time of your initial diagnostic surgery/biopsy and has been stored in a hospital laboratory. This screening procedure is a test, called Rb1 screening test, to see if you qualify to take part in a main research study of either Phase I or surgical portion. If you sign the screening consent, you are only agreeing to have this test done by allowing your study doctor to obtain your tissue sample from pathology. If the test result shows that you are 1 NCI Protocol \#: PBTC-050 Version Date: September 4, 2018 Updated Date: September 26, 2018 eligible to take part in the research study, a separate informed consent will be provided to you describing full in details about the study and the investigational drug(s). Agreeing to have your tumor tissue screened does not oblige you to agree to participate in the main research study. You can still decide not to participate in the main research study. 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 your tumor from growing. We want to find out whether your tumor has Rb1 protein or not so that we can consider you for participation in the main study. Up to 70 people, between the ages of 1 and 21 years old, will be screened throughout the United States. Another purpose of this consent is we are asking you to let us store any leftover tumor samples after the screening test is completed at Cincinnati Children's Hospital Medical Center (CCHMC) for possible use in future research. This is optional and only if you agree, your tumor samples will be kept at a central place, called the Pediatric Brain Tumor Consortium Central Review and Biorepository (PBTC CRB).

This research study has two portions: Phase I and Surgical study. For now, we will talk to you about participation in the surgical portion of the study. Once you finish the surgical study, you will be asked again if you like to continue for participation in the Phase I study. The information about the participation in the Phase I study will describe more in details in the Phase I consent.  
Updated Date: September 26, 2018 The purpose of this surgical study is to test the amount of a study drug called ribociclib in your tumor and blood prior and during surgery for removal of the recurrent tumor. We have also learned that this study drug works better if your tumor has an intact Rb1 protein. You have been approached for this study because we know that you will have your brain tumor tissue removed within a few weeks and that this Rb1 protein is present in your tumor tissue that is removed during this surgery. Ribociclib has not been approved by the FDA (the U.S. Food and Drug Administration) for the treatment of brain cancer, therefore, is considered experimental for this trial. But it has been approved for other use. This drug has been tested for safety in adults and children. About 3 to 6 people, between the ages of 1 and 21 years old, are expected to taking part in this surgical study.

This research study has two portions: Phase I and Surgical study. This consent is for Phase I study and we will talk to you about participation in the Phase I portion of the study. Updated Date: September 26, 2018 The purpose of this study is to test the safety of study drugs called ribociclib and everolimus when given in combination. Each of these drugs has been tested in children as monotherapy but not as combination therapy. This study tests different doses of the drugs when given in combination to see which dose is safer in children.  
We have also learned that ribociclib works better if your tumor has an intact Rb1 protein. You have been approached for this study because we know that this Rb1 protein is present in your tumor tissue. Ribociclib and everolimus have not been approved by the FDA (the U.S. Food and Drug Administration) for the treatment of brain cancer; therefore, they both are considered experimental drugs for this trial. But they have been approved for other uses. These drugs have been tested for safety in adults and children. About 45 people, between the ages of 1 and 21 years old, are expected to take part in this Phase I study.

The purpose of this screening consent is to perform a test on a sample of your tumor tissue which was removed at the time of your initial diagnostic surgery/biopsy and has been stored in a hospital laboratory. This screening procedure is a test, called Rb1 screening test, to see if you qualify to take part in a main research study of either Phase I or surgical portion. If you sign the screening consent, you are only agreeing to have this test done by allowing your study doctor to obtain your tissue sample from pathology. If the test result shows that you are 1 NCI Protocol \#: PBTC-050 Version Date: September 4, 2018 Updated Date: September 26, 2018 eligible to take part in the research study, a separate informed consent will be provided to you describing full in details about the study and the investigational drug(s). Agreeing to have your tumor tissue screened does not oblige you to agree to participate in the main research study. You can still decide not to participate in the main research study. 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 your tumor from growing. We want to find out whether your tumor has Rb1 protein or not so that we can consider you for participation in the main study. Up to 70 people, between the ages of 1 and 21 years old, will be screened throughout the United States. Another purpose of this consent is we are asking you to let us store any leftover tumor samples after the screening test is completed at Cincinnati Children's Hospital Medical Center (CCHMC) for possible use in future research. This is optional and only if you agree, your tumor samples will be kept at a central place, called the Pediatric Brain Tumor Consortium Central Review and Biorepository (PBTC CRB).

This research study has two portions: Phase I and Surgical study. For now, we will talk to you about participation in the surgical portion of the study. Once you finish the surgical study, you will be asked again if you like to continue for participation in the Phase I study. The information about the participation in the Phase I study will describe more in details in the Phase I consent.  
Updated Date: September 26, 2018 The purpose of this surgical study is to test the amount of a study drug called ribociclib in your tumor and blood prior and during surgery for removal of the recurrent tumor. We have also learned that this study drug works better if your tumor has an intact Rb1 protein. You have been approached for this study because we know that you will have your brain tumor tissue removed within a few weeks and that this Rb1 protein is present in your tumor tissue that is removed during this surgery. Ribociclib has not been approved by the FDA (the U.S. Food and Drug Administration) for the treatment of brain cancer, therefore, is considered experimental for this trial. But it has been approved for other use. This drug has been tested for safety in adults and children. About 3 to 6 people, between the ages of 1 and 21 years old, are expected to taking part in this surgical study.

This research study has two portions: Phase I and Surgical study. This consent is for Phase I study and we will talk to you about participation in the Phase I portion of the study. Updated Date: September 26, 2018 The purpose of this study is to test the safety of study drugs called ribociclib and everolimus when given in combination. Each of these drugs has been tested in children as monotherapy but not as combination therapy. This study tests different doses of the drugs when given in combination to see which dose is safer in children.  
We have also learned that ribociclib works better if your tumor has an intact Rb1 protein. You have been approached for this study because we know that this Rb1 protein is present in your tumor tissue. Ribociclib and everolimus have not been approved by the FDA (the U.S. Food and Drug Administration) for the treatment of brain cancer; therefore, they both are considered experimental drugs for this trial. But they have been approved for other uses. These drugs have been tested for safety in adults and children. About 45 people, between the ages of 1 and 21 years old, are expected to take part in this Phase I study.

The purpose of this screening consent is to perform a test on a sample of your tumor tissue which was removed at the time of your initial diagnostic surgery/biopsy and has been stored in a hospital laboratory. This screening procedure is a test, called Rb1 screening test, to see if you qualify to take part in a main research study of either Phase I or surgical portion. If you sign the screening consent, you are only agreeing to have this test done by allowing your study doctor to obtain your tissue sample from pathology. If the test result shows that you are 1 NCI Protocol \#: PBTC-050 Version Date: September 4, 2018 Updated Date: September 26, 2018 eligible to take part in the research study, a separate informed consent will be provided to you describing full in details about the study and the investigational drug(s). Agreeing to have your tumor tissue screened does not oblige you to agree to participate in the main research study. You can still decide not to participate in the main research study. 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 your tumor from growing. We want to find out whether your tumor has Rb1 protein or not so that we can consider you for participation in the main study. Up to 70 people, between the ages of 1 and 21 years old, will be screened throughout the United States. Another purpose of this consent is we are asking you to let us store any leftover tumor samples after the screening test is completed at Cincinnati Children's Hospital Medical Center (CCHMC) for possible use in future research. This is optional and only if you agree, your tumor samples will be kept at a central place, called the Pediatric Brain Tumor Consortium Central Review and Biorepository (PBTC CRB).

This research study has two portions: Phase I and Surgical study. For now, we will talk to you about participation in the surgical portion of the study. Once you finish the surgical study, you will be asked again if you like to continue for participation in the Phase I study. The information about the participation in the Phase I study will describe more in details in the Phase I consent.  
Updated Date: September 26, 2018 The purpose of this surgical study is to test the amount of a study drug called ribociclib in your tumor and blood prior and during surgery for removal of the recurrent tumor. We have also learned that this study drug works better if your tumor has an intact Rb1 protein. You have been approached for this study because we know that you will have your brain tumor tissue removed within a few weeks and that this Rb1 protein is present in your tumor tissue that is removed during this surgery. Ribociclib has not been approved by the FDA (the U.S. Food and Drug Administration) for the treatment of brain cancer, therefore, is considered experimental for this trial. But it has been approved for other use. This drug has been tested for safety in adults and children. About 3 to 6 people, between the ages of 1 and 21 years old, are expected to taking part in this surgical study.

This research study has two portions: Phase I and Surgical study. This consent is for Phase I study and we will talk to you about participation in the Phase I portion of the study. Updated Date: September 26, 2018 The purpose of this study is to test the safety of study drugs called ribociclib and everolimus when given in combination. Each of these drugs has been tested in children as monotherapy but not as combination therapy. This study tests different doses of the drugs when given in combination to see which dose is safer in children.  
We have also learned that ribociclib works better if your tumor has an intact Rb1 protein. You have been approached for this study because we know that this Rb1 protein is present in your tumor tissue. Ribociclib and everolimus have not been approved by the FDA (the U.S. Food and Drug Administration) for the treatment of brain cancer; therefore, they both are considered experimental drugs for this trial. But they have been approved for other uses. These drugs have been tested for safety in adults and children. About 45 people, between the ages of 1 and 21 years old, are expected to take part in this Phase I study.

To see if patients with brain tumors can safely take these drugs combination, and to find the best dose that patients can take safely To learn what kinds of side effects happen in patients with brain tumors when they take ribociclib and everolimus in combination To learn how patients with brain tumors handle the combined study drugs, ribociclib and everolimus (for examples, how much drugs are absorbed, how the body breaks down the drugs). This is called a pharmacokinetic study, or PK study.
Clinical trial: NCT03387020
Section: Voluntary Participation
Subsections: Model Consent Form - **Screening Consent**|Is My Participation In This Screening Procedure Voluntary?

Study Title for Study Participants: Screening Test to find out the presence or absence of retinoblastoma protein (Rb1) *in patients* with brain tumors Official Study title for Internet Search on http://www.ClinicalTrials.gov PBTC-050: A Phase I and Surgical Study of Ribociclib and Everolimus (RAD001) in Children with Recurrent or Refractory Malignant Brain Tumors "You" *refers to 'you' or 'your child' throughout this document. If you are the guardian of a* minor or of a person under legal disability who is being asked to participate in this screening study, you may give consent on his/her behalf.

Yes. Taking part in this screening procedure is voluntary. No matter what you decide to do, it will not affect the medical care you would normally receive from your doctor.
Clinical trial: NCT03387020
Section: Withdrawal from Study
Subsections: Can I Stop Being In The Study?|What If I Change My Mind?|Can I Stop Taking Part In This Study?|Can I Stop Taking Part In This Study?|Can I Stop Taking Part In This Study?|Can I Stop Taking Part In This Study?

Yes, you may withdraw this consent and discontinue your participation in the screening study at any time. To withdraw your consent, you must contact the study doctor and tell him/her that you are changing your mind. NCI Protocol \#: PBTC-050 Version Date: September 4, 2018 Updated Date: September 26, 2018 If you change your mind and your samples have already been tested, those results will still remain part of the overall research data.  
What are the possible risks, side effects, and discomforts of this screening study?  
Since your tumor tissue has already been collected during the surgery, there are no additional risks to you involved with this screening test. However, there is a possibility that completing this test will result in exhaustion of tumor tissue.

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 repository 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.

Yes. You can decide to stop at any time. If you are thinking about stopping or decide to stop for any reason, tell your study doctor and he or she will tell you how to stop safely. It is important that any risks from the study drug can be evaluated by your study doctor. Your study doctor may discuss what follow-up care and testing could be helpful for you. If the study drug is stopped, 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 at any time if your doctor believes:
If your health changes and the study is no longer in your best interest If new information becomes available If you do not follow the study rules If the study is stopped by the sponsor, IRB, Novartis (the drug supplier) or FDA.  
Updated Date: September 26, 2018 What are my rights in this study? 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). What are the costs of taking part in this study? Ribociclib will be supplied at no charge while taking part in this study. The cost of getting ribociclib ready and giving it to you may not be paid by the study sponsor so you or your insurance company may have to pay for this. It is possible that ribociclib 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/your insurance company will not be charged for procedures that are being performed for research purposes only. You will not be paid for taking part in this study. What happens if I am injured because I took part in this study? It is important that you tell your study doctor, *(Physician's Name)* if you feel that you have been injured because of taking part in this study. You can tell the doctor in person or call him/her at (physician's telephone number). 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. Novartis will not provide payment for any medical expenses which you may incur as a result of your participation in this study. No other type of compensation will be provided by Novartis. 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.

Yes. You can decide to stop at any time. If you are thinking about stopping or decide to stop for any reason, tell your study doctor and he or she will tell you how to stop safely. It is important that any risks from the study drug can be evaluated by your study doctor. Your study doctor may discuss what follow-up care and testing could be helpful for you. If both drugs are stopped, 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 at any time if your doctor believes:
If your health changes and the study is no longer in your best interest If new information becomes available If you do not follow the study rules If the study is stopped by the sponsor, IRB, Novartis (the drug supplier) or FDA.
What are my rights in this study? 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).

Yes. You can decide to stop at any time. If you are thinking about stopping or decide to stop for any reason, tell your study doctor and he or she will tell you how to stop safely. It is important that any risks from the study drug can be evaluated by your study doctor. Your study doctor may discuss what follow-up care and testing could be helpful for you. If the study drug is stopped, 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 at any time if your doctor believes:
If your health changes and the study is no longer in your best interest If new information becomes available If you do not follow the study rules If the study is stopped by the sponsor, IRB, Novartis (the drug supplier) or FDA.  
Updated Date: September 26, 2018 What are my rights in this study? 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). What are the costs of taking part in this study? Ribociclib will be supplied at no charge while taking part in this study. The cost of getting ribociclib ready and giving it to you may not be paid by the study sponsor so you or your insurance company may have to pay for this. It is possible that ribociclib 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/your insurance company will not be charged for procedures that are being performed for research purposes only. You will not be paid for taking part in this study. What happens if I am injured because I took part in this study? It is important that you tell your study doctor, *(Physician's Name)* if you feel that you have been injured because of taking part in this study. You can tell the doctor in person or call him/her at (physician's telephone number). 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. Novartis will not provide payment for any medical expenses which you may incur as a result of your participation in this study. No other type of compensation will be provided by Novartis. 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.

Yes. You can decide to stop at any time. If you are thinking about stopping or decide to stop for any reason, tell your study doctor and he or she will tell you how to stop safely. It is important that any risks from the study drug can be evaluated by your study doctor. Your study doctor may discuss what follow-up care and testing could be helpful for you. If both drugs are stopped, 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 at any time if your doctor believes:
If your health changes and the study is no longer in your best interest If new information becomes available If you do not follow the study rules If the study is stopped by the sponsor, IRB, Novartis (the drug supplier) or FDA.
What are my rights in this study? 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).