Understanding Clinical Trials

okay the wet the American brain-tumor Association once again is pleased to welcome you back to our webinar series as I mentioned our webinar today is on understanding clinical trials my name is Jennifer Westland I’m the associate director of national programs and services here at the American brain tumor association and I’m really delighted to introduce our speaker today dr. Bruce is a neurosurgeon and the Edgar m has been professor of Neurological Surgery the vice chairman of academic affairs director of the Bartoli brain tumor research laboratory and co-director of the brain tumor Center at Columbia University there he is a leading authority on complex tumors of the brain and skull base dr. Bruce leads a multidisciplinary effort as co-director of the brain tumor center and director of skull base surgery specializing in the surgical treatment of gliomas meningioma x’ pituitary tumors skull base tumors craniopharyngioma x’ and pineal tumors his surgical expertise includes extensive experience with minimally invasive techniques and stereotactic surgery as well as surgical alternatives such as radiosurgery this broad expertise allows treatment to be tailored and optimized for individual patients according to their needs as co-director of the brain tumor center dr. Bruce also leads an NIH funded translational brain tumor research effort with interest in immunotherapy and drug delivery systems and in addition to his laboratory research interests he’s very actively involved in experimental clinical protocols for the treatment of brain tumors so again thank you so much for being with us and joining us from New York this afternoon where I know the the weather is a little concerning you can go ahead and begin your program okay Thank You Jennifer I am delighted to be here today and by though I can’t see you big greeting to all of those out there who are tuning in on this on this Saturday I wanted to just say worried about the American brain tumors Association this is a really a wonderful organization it’s helped many people and families in fact when I first started in research many years ago the ABT a gave me some of my initial research funding and has enabled us to have really a very big laboratory now that has made many contributions to this field and so I’m always grateful for everything they have done and I know they’ve taken care of many of my patients over the years and helped them with problems and questions so I’m delighted that they organized this webinar for us today now should I add that this is an exciting time to be in the brain tumor field there are a lot of new advances in treatment and diagnosis many of them leading to clinical trials and a lot of new opportunities are opening up in the future what we’re going to speak about today is sort of navigating that complicated area of clinical trials and clinical trials can be very confusing for you out there so I’m going to just give you a little background on brain tumors most of which you already know but just to put this in some context and then we’ll think about some of the intricacies of clinical trials I think you know the brain tumor facts that there forty-thousand brain tumors are diagnosed each year it’s the second leading cause of cancer death for young people and the fact that it’s increased in in young people but also affects everyday function so there’s a really a compelling need to improve the treatment for these we have some evidence that the incidence of these is increasing especially in the elderly and it’s still not clear whether that’s happening because we really don’t know what causes brain tumors but this is still an area of very active investigation glioblastoma malignant brain tumors are the most common types of they can not only be life-threatening but threatened important areas of the brain they can spread to other parts of the brain or spinal cord but they really don’t spread to other parts of the body compared to other types of cancers where the biggest problem is metastatic disease and spread that’s less of a problem for these kind of tumors we do know that they invade the brain so they get into the brain tissue and that’s really where the treatment needs to be censored and currently treatment options are involved surgery radiation chemotherapy and to an extent experimental treatments and that really is the basis for clinical trials tumor

grading you know tumors gliomas are graded into low grade or slow growing tumors versus high grade or fast growing tumors and that does real blastoma being most common type of a high grade tumors the problem with low-grade tumors that they can progress to high grades some of you out there may have been have a diagnosis of glioblastoma or you may have a lower grade tumor such as an astrocytoma or an oligodendroglioma or some kind of intermediate grade or malignant glioma what we’re going to talk about with clinical trials they really applies to all of those areas in in terms of how to think about clinical trials and how to choose one that may be best for you now or at least for malignant gliomas and for glioma is in general the current standard of care is some form of surgery it can be a limited form of surgery where you simply have a biopsy to establish the diagnosis or you may have a resection that you may have an open operation where the skull is open and you actually try to remove as much tumor as possible the decision about what to do biopsy versus resection usually made by your surgeon and that’s based on balancing the risks and benefits of that particular procedure if your tumor is malignant then you are facing weeks of radiation therapy and for many types of malignant gliomas Temodar chemotherapy is normally indicated so the standard current standard treatment is some form of surgery followed by radiation and then timid or chemotherapy with surgery the goals are generally to remove as much as possible at the tumor but sometimes again that’s limited and a biopsy may be the only thing that is feasible the limitation in how much tumor can vineyard is that tumor cells invade the brain and they kind of intermix with normal brain cells so you try to remove those tumor cells that are invading you run the risk of damaging the normal cells and creating neurological problems that can be anything from speech problems or weakness or walking problems so those kind of decisions about how much tumor to remove are based on your surgeon’s judgment surgery is also used to establish the diagnosis meaning some of the tumor that’s removed as sent to the pathologist for them to make the diagnosis the other thing that surgery does is it provides access for other treatments meaning many times it’s useful to try and remove as much tumor as possible so that the treatment that’s given later whether it’s radiation some form of chemotherapy or some experimental treatment has the best chance of working if there’s lesser amounts of tumor available radiation therapy involves what we call external x-ray beams meaning your your head is in the x-ray machine you know I simply turned the x-rays on for a short period of time and this type of treatment is very good for invasive malignant tumors so that those tumor cells that are invading into the brain that can’t be removed with surgery are often very effectively treated with radiation therapy because of the side effects that you can get from radiation radiation has to be given in small amounts so you get a little bit of radiation day four usually up to about thirty treatments and the type of complications that are common or can be hair loss or tiredness or skin irritation but these are generally very well tolerated and can be treated very well chemotherapy is usually given either after radiation sometimes during radiation and the effect of chemotherapy can be very varied normally the biggest problems with chemotherapy is that it suppresses your bone marrow meaning chemotherapy can kill some of the blood cells that you have and that lead to anemia and tiredness or infections if some of the white blood cells are affected to some degree you may have some nausea vomiting fatigue chemotherapy is also given on an intermittent schedule meaning it’s given at one point and then you’re given and then it may not be given for several days or several weeks later and in some cases it’s used instead of radiation and children since children are more vulnerable to the side effects of

radiation okay so conventional chemotherapy as we know it now the most effective chemotherapy for brain tumors is temozolomide and we know that temozolomide works because it has been proven in clinical trials so at one point temozolomide was an experimental drug it was tested in clinical trials and as part of the testing we were able to find out that some of the changes in the tumor some of the biological changes in the tumor actually correlate with how well the drug is going to respond so temozolomide has given him for most patients so that the current standard of care for someone with a malignant glioma is to remove as much of the tumor as possible of radiation and then amadon and these this current standard of treatment is is useful for pretty much everybody with a brain tumor but there is a a significant improvement when seminar is used with surgery and radiation so that’s why we come up with this current standard of surgery radiation and Temodar okay now let’s talk about clinical trials clinical trials are normally what you think about when you’ve already have standard treatment and your tumor begins to grow back that’s not true in all cases but that’s that’s the most common time that people begin to look for clinical trials sometimes you look for a clinical trial before you’ve gotten any treatment at all and there are some clinical trials out there that are designed for that but clinical trials are basically research studies that are based on experimental evidence by that I mean some scientists in the laboratory came up with an idea about what might be a good treatment for brain tumors and they tested it in the laboratory both on tumor cells that are growing in a test tube then they test it in in some animal studies and they may use some preliminary or pilot studies in patients and if the if the information that they’re getting looks promising if it looks like that treatment could be effective for brain tumors then they a clinical trial is organized and before a clinical trial can actually open up before a patient can actually be on a clinical trial the investigator whoever’s running the clinical trial has to write and approve protocol in other words they have to write a very detailed explanation of how that treatment is going to occur who’s going to get it how they’re going to repel it’s going to occur what are the risks and benefits and that protocol is then submitted to a board for approval and I’ll talk a little bit more about that a moment but this highly regulated protocol is designed to ensure the safety and protection of patients in other words you don’t want subject to a clinical trial or experimental treatment anytime anyone just has what’s a good idea that idea has to be fleshed out a little bit more before you can simply begin to treat patients with it and so that’s why clinical trials are as strongly organized as they are now there are many different types of trials the ones that most people are interested in and thinking about are clinical trials that are therapeutic meaning a clinical trial that’s going to test something to actually kill the brain tumor or to to treat the tumor and that can be testing a new drug may be testing a new form of radiation or a different way that the radiation is given or it could test a a surgical protocol where the surgery is performed in a very specific manner there are also sometimes devices at every everything from-from different electromagnetic field devices to other types of devices to actually deliver drugs that can be tested as well but the therapeutic trials that are mostly designed for a treatment of the tumor there can be diagnostic trials where a protocol is put together to try and diagnose what kind of tumor somebody has maybe before they even have surgery this may be a little bit more relevant to other types of memories rather than brain tumors these are more common or breast tumors or lung tumors for instance there can be clinical trials

looking at quality of life so that a trial may look at either a new type of treatment or an old treatment and try and measure the quality of life that the patient has so so you can measure outcomes such as how long it takes until the tumor grows back or you know different components like that but you can just you can also measure the quality of life that is how well does the patient tolerate this particular treatment and you know is their quality of life better as a result of it there are clinical trials on preventive treatment so where where you actually prevent a tumor from happening and this is this occurs with things like vaccines again there’s not as relevant to brain tumors but certainly preventive treatments are more common for things like lung cancer where you are trying to stop smoking or colon cancer where you alter your diet to try and prevent a tumor from occurring there can also be clinical trials for screening where groups of people are screened to see whether they have the disease or not this is you’re most familiar with this with breast cancer where people undergo mammograms to screen for whether they have a tumor right now there aren’t really many useful screening tools for brain tumors mostly because they’re not common enough or or to justify the the kind of screening procedures that are needed if we look to the future and advances of treatment of gliomas this is sort of the area where a lot of the attention is focused for clinical trials this is sort of the breeding ground for the new ideas for what the future treatments are going to be and I don’t think we have the time in this webinar to talk about all of those but I want to briefly mention some of the really very exciting areas nowadays where brain tumor research is focused and where the future clinical trials are going to come from first of all there are many advances in the surgery of gliomas the techniques that surgeons use nowadays are safer than ever and more able than ever to maximize amount of tumor that’s removed this is everything from special dyes that are used to to distinguish the tumor from their from the normal brain two other types of techniques with stereotactic guidance and minimally basic techniques that are designed to remove as much tumor as possible as safely as possible so so the advances in surgery have never been better there is also work done on drug delivery systems in particular something called convection enhanced delivery where the drug is given directly into the tumor directly into the brain through a catheter that is surgically implanted the benefit of this is that drug goes right into the tumor without going throughout the rest of the body as you would otherwise need with something that was given intravenously or in a pill form the drug is given right directly into the tumor so you have I avoid all of the side effects of the drug and you’re able to get very large amounts of drug into the tumor another big field of investigation is chemotherapy that is looking for new drugs and new targets within the tumor so chemotherapy is being designed their sort of design or chemotherapy where scientists are trying to look at people at patients individual tumors and try and find out what drugs would be best for that individual tumor and there’s a lot of work being done on that using molecular biology and genetics and it’s hoped that and someday in the future you’ll have a a treatment plan that is designed specifically for your tumor now there are also a lot of novel drug that are being developed that are designed to look at different targets in the tumor by that I mean there are drugs that are targeting the blood vessels in the tumor there are drugs that are preventing the tumor from invading into the brain there are also drugs that that block the tumor cells from simply from growing or proliferation and there are many new drugs that come out all the time and these are also the basis for a lot of the clinical trials that you’ve probably heard about now another big area is immunotherapy this is an area

that uses your body’s own immune system to combat the tumor so there this is like vaccines and antibodies what we know is that when a tumor grows in the brain it creates a irritation in the brain that actually stimulates the immune system so when you have a tumor growing your immune system actually tries to get rid of the tumor it kind of sees it as a foreign invader in the brain the problem is is that the tumor begins to release substances that actually block the immune system so a lot of the work that’s being done with vaccines and antibodies is designed to make that immune response against the tumor stronger so that it’s able to to kill the tumor cells before the tumor cells can actually block that immune response another area of interest is gene therapy and this is sort of an extension of the whole field of molecular biology where where investigators can look at the the genes and the molecules within the tumor that are causing the problem and there’s some very clever techniques that are being done to actually block specific genes that are giving the wrong instructions to the tumor and giving the tumor instructions to grow when in fact you you want the instructions to be just the opposite there are also advances in radiation therapy of everything from different types of radiation such as proton beam there’s radio surgery there’s other ways of giving radiation with different treatment schedules and these again are designed to try and minimize the amount of side-effects that radiation is causing in the normal brain now in general clinical trials are mostly for tumors that are recurrent in other words tumors that have grown back after standard treatment but there are also some clinical trials that are designed for patients before they have received any other treatment so for newly diagnosed tumors and sometimes that is done because the treatments that you get can sometimes interfere with some of these new experimental treatments so that’s usually up to the investigator to design a trial either for recurrent tumor or for a new tumor now most clinical trials are found at most of the major medical centers because of the infrastructure that’s needed to conduct a clinical trial you may see it in some community hospital but mostly is your conductor that major medical centers usually those that are associated with a university or other institution and it’s important to have a knowledgeable team of physicians so that’s why these are mostly concentrated in in big centers I think in general clinical trials are a good idea because it helps keep patients involved in their own treatment most of the people who are conducting clinical trials are very motivated to see their treatments come to fruition so they they take very good care of the patients they’re very actively involved and it’s a way to get a lot of attention as you’re getting treatment for your tumor clinical trials are set up at least the the therapeutic clinical trials with clinical trials for treatment are set up in one of the phases phase one phase two and phase three and you can’t go to the Phase two unless you’ve done a phase one you can’t go to a phase three unless you’ve done a Phase two but a phase one is the earliest stage in testing a drug so if you have a new drug and you want to test it in a clinical trial you have to organize it as a phase one trial and what the phase one trial does is that it is used to find out what the best dose of the drug is if you’ve never given this drug before you don’t know how much to give you don’t know how often to give it so normally what the investigator will is start out at a very low dose to avoid the risk of causing any side effects so you start out a very low dose and you give this low dose to a few patients if the patient’s tolerate it well then you can increase the dose and then you give that higher dose to a few more patients and you keep increasing the dose after every few patients or so until you begin to reach a dose that begins to cause side effects so by gradually increasing the amount of drug that you give you can begin to find out at what point that drug begins to cause side effects so a

phase one trial is designed in this sort of increasing dose manner so that the investigator can focus on the safety and the side effects of the drug because you may be starting at low doses of the drug those low doses while they may avoid the side effects they also may not be the most effective at killing the tumor usually you want as high a dose as possible to kill the tumor cells and you’re balancing that benefit of killing the tumor cells with the side effects that it can cause so by starting out at a low dose and coming to a higher dose you are establishing the safety and because of this kind of strategy you really are not maximally designed to look at effectiveness in other words if you’re in a phase one trial you may very well get a dose that’s lower than what may turn out to be the optimal dose but unfortunately that’s the way the trial has to be done because what’s really most important is establishing the safety and then later on trying to establish how well the drug works that’s really what a Phase two trial is for the Phase two trial takes the information from the phase 1 trial where the investigator has has found out what the best dose of the drug is that is the drug the drug that begins to cause side-effects but has the best chance of killing tumor cells so using this dose that’s been established the phase 2 trial will look at a number of patients anywhere from 20 to 40 patients and just determine with this one drug dose whether there is an effect or not and if there is an effect then a phase 3 trial is done in the phase 3 trial is what we call a randomized trial to compare experimental treatment to the best standard of treatment by that we mean we take the dose of drug that was validated in the in the phase 2 trial and we look at a group of patients and we give some of them the drug and some of them we just give whatever standard treatment they would otherwise get and this is using randomize meaning you essentially flip a coin at the time of treatment to see whether you’re going to get the experimental treatment or whether you’re going to get this standard treatment and then the trial continues and over time you then compare whether the experimental troop at whether the experimental group did better than the standard treatment group and if the experimental troop if the experimental group did better well then you have a clinical trial that shows that your drug is working better than the best treatment available and usually that kind of drug will get approved for treatment now who sponsors clinical trials who who’s able to oversee these clinical trials as I mentioned before the most common are usually individual institutions that is medical centers and universities and regardless of who is sponsoring the clinical trial they’re overseen by an institutional review board or the IRB and the IRB is designed to make sure that whatever clinical trial is being conducted that that clinical trial is is safe that it protects patients and that it utilizes good science in other words that if somebody’s going to do a clinical trial we have to make sure that what they’re testing actually makes sense and and their he experimental laboratory studies that were done are actually reviewed to make sure that that the clinical trial is going to have some reasonable chance of success in addition to individual institutions there are cooperative groups that work together to begin to conduct these clinical trials that is they sort of combine forces this includes everything from you may have heard of swag or the southwestern Oncology Group II cog which is the eastern cooperative group the CCG which is the children’s cancer group or the abt C which is the adult brain tumor consortium these are all groups around the United States that run these kind of trials in addition the federal government or the NIH can conduct criminal clinical trials and you also see industry by that I mean there are pharmaceutical companies that sometimes conduct their own clinical trial to see whether a drug that they are developing

is likely to work what to think about in a clinical trial is it is you know how to choose a clinical trial you know again these are all experimental treatments there’s no single experimental treatment that is right or wrong for you if we knew that the treatment worked it would no longer be experimental so by virtue of the fact that it’s in a clinical trial means it’s an experimental treatment and you want to know do I qualify the trial do I have the right type of tumor do I have the previous treatments that I have but they make me still eligible for this you want to know who is running the trial what is the where the investigators coming from who do they belong to an institution is it pharmaceutical where will the trial be performed do I have to travel somewhere will it be at the primary institution where the where the trial is being set more importantly what are the risks and benefits what kind of risks do we think we have now most of the clinical trials are designed to begin to discover what risks there are but there should be some preliminary evidence about what kind of risks you may be facing and obviously you want to know the benefits how likely is this going to work if it’s a phase one trial it may be that we don’t know the answer to that if it’s a phase two or phase three trial there well there’s already a lot of preliminary evidence you may have some idea about whether the treatment is going to benefit you next you want to know what the alternatives are if you don’t do this experimental treatment what other treatment options are available to you you want to know about additional costs because of their experimental treatments most times your insurance company will not cover any cost most clinical trials before they actually start the investigator will try and get funding either research funding from a group like the American brain-tumor Association or the federal government so they will have money available to pay for the treatment so if the patient doesn’t have to pay for that that’s not always the case so you certainly want to ask about that then you want to know what are your responsibilities normally when you agree to enter in an experimental protocol it’s important to make sure that you follow through with all of the regulations because these are carefully regulated because there are legal aspects for that for this it’s important that you follow all the steps that the investigator needs to do because there may be additional blood tests or maybe other types of pests and if you don’t have those tests done then you may not be able to continue in the clinical trial and these tests are usually done for a reason they’re done to try and figure out whether the drug is going to work better their design they may be designed to help protect you from side effects but it’s important to know what your responsibilities are how often you’re going to need to come for follow-up how often you’re going to need to come for additional tests you want to know about placebo versus treatment by placebo we mean that when you reach a certain level of trial usually in like a phase 3 trial the investigators may be comparing whether their drug works versus a placebo and a placebo as you know it’s just like a sugar pill it has no effect but it’s designed to remove any bias in other words sometimes when you’re enrolled in a clinical trial and you know you’re getting the treatment you may actually do better because you think you’re doing better and there are all kinds of biases that investigators have when they know somebody’s getting treatment so a placebo is designed to sort of counteract that the other thing is finding out what previously results there’s been with this treatment unless you’re the first person treated in which case you wouldn’t want to know more about the laboratory and and investigational information done within with the test tube’s or the animal treatments that were done as and in the laboratory when you participate in the clinical trial you should be given an information sheet and that information sheet should tell you all about the clinical trial it should give you some idea of the risks and benefits it should spell out what responsibilities you have and this information shoot can sometimes be somewhat complicated so you want to make sure you go over this with your family and your your doctor you then go through a screening process and this screening process is to find out whether you’re eligible and the screening process may be used to find out what type of tumor you have to see if the type of tumor you

have is eligible it may look at other medical problems that you have for instance if you have heart disease and and the experimental drug is is dangerous to the heart then you may not be eligible on that basis so the screening process is designed to make sure that the the treatment that’s being investigated is the right one for you it doesn’t have to give you consent this is a legal document to say that you understand the risks and benefits and alternatives of treatment but it’s important to know that you have rights that you can opt out of this at anytime just because you’re in a clinical trial just because you’re receiving the experimental drug hopefully you’ll want to stay with the trial the whole way because that’s how we get the most benefit from understanding whether a drug is working or not but it’s always your right to opt out of the treatment at any time where to find out about clinical trials your your doctor is a good source of this the Internet certainly the ABT a website has information on this the federal government @ww clinical trials.gov there are there are many ways to find out about this but I would always start with your physician because they’re going to be able to give you the most information about personalizing what clinical trials to look into there are a number of FDA considerations that’s the Federal Drug Administration and they are the regulatory agency that oversees any kind of new drugs they look at experimental drugs and experimental drugs are drugs that are new but are unproven and whether they work or not and the FDA has to decide whether a new drug is safe and whether it works or they will approve it off-label drug use is something that is basically using a drug for something then other than what it was intended for for instance if if someone wanted to take a chemotherapy drug that’s been used for lung cancer and use it for a brain tumor that’s a considered an off-label drug use in other words the chemotherapy is not designed for the brain tumor but it may be an investigational use of it and therefore would be considered off-label you can also have what is known as compassionate use and that is because somebody may have no other options available and because the this drug may have some need for work it may be very useful you can get what’s called passionate use and that is where you may not be eligible for a trial for a particular drug but because you have no other options you get compassionate use and receive the drug anyway sometimes difficult to do that but that’s something that the FDA oversees and ultimately the FDA is responsible for giving approval after a clinical trial so they are the ones that ultimately decide whether people are going to have permission to use this drug for a specific purpose and that is going to be based on whether a clinical trial shows safety and effectiveness it’s important to have realistic expectations for clinical trials we know that with conventional chemotherapy and radiation that many of these tumors are going to grow back so we know that the new approaches are promising but they may have major obstacles so you we want to be very hopeful about a clinical trial but we always have to keep in mind that it is experimental and you want to keep your expectations realistic and it’s important when you’re doing this to communicate with your healthcare team you need a reputable specialists and there are many excellent brain tumor specialists out there you can find them either through the primary care doctor or on the Internet and these people can be very effective in helping you navigate through all these difficult questions some practical things keep a notebook write down your questions so that when you’re seeing the doctor or going to learn about the clinical trial you and your family have compiled a list of questions so that you don’t forget once you’re in the doctor’s office make sure that you’re that the instructions are understood make sure you understand what it is that is required of you what the expectations are and I think it’s very helpful to have an honest dialogue with your family have your family involved make sure they they help you make this decision and keep those lines of communication open be skeptical of anecdotes no matter how well-meaning once you you probably all familiar this once you diagnosed with a brain tumor you hear all kinds of stories from somebody’s uncle or cousin

that this happened or that happened and and sometimes it’s good sometimes it’s bad but I think you have to keep in mind that everybody’s brain tumor is different no matter what someone else’s experience was or has been doesn’t mean that it applies to you so be skeptical of those anecdotes don’t be afraid of second opinions especially if you’re getting signals that are are hard to understand if you’re getting disagreements among your doctors you don’t be afraid of having a second opinion and overall certainly consider clinical trials at academic centers if you’re considering experimental treatment and considering moving on after your conventional treatment has been done certainly a clinical trial is a reasonable thing to do and so the questions to be answered before in a clinical trial is surgery going to be involved in other words as a tumor need to be removed again before the trial starts what are the risks what other treatments can be considered if this treatment is not done can the treatment wait how urgent is this and also what happens if we decide against having treatment when it comes down to a treatment decision it’s useful to keep a copy of your own records and scans although there’s a big move to electronical medical records that still is in a in a an early stage and it’s still helpful to have copies of your own records and scans if you’re going for second opinions if you’re looking into a clinical trial the more information you have easier it is to decide whether you’re eligible and it’s easier it is for a new investigator a new doctor who’s meeting you for the first time to get the best understanding of your particular situation obviously understand your choices know what’s available to you know whether by moving ahead with this decision for a clinical trial or standard decision understand what your choices are and again share your concerns with family and health care team I think you’re hearing a and over a theme over and over and that is communication with your doctor’s your family your healthcare team what about recurrences what about your tumor recurring or growing back these are inevitable most of the treatments that are done can slow down a tumor and many times the tumor is going to grow back at some point in the future again having a knowledgeable team of physicians as the is the important thing but then considering experimental therapy in a in a clinical trial that’s the best way to go so as we begin to conclude this discussion I want to to emphasize again how useful and important these clinical trials can be especially for those with brain tumors because once you get app once you finish with surgery radiation and Temodar most of the treatments available after that are on an experimental basis so let me begin to wrap up here by telling you some quality of life and practical suggestions and this is true for anybody who’s interested in clinical trial but also true for anybody with a brain tumor in general keep a list of things to do utilize your friends and family write things down keep your notebook not only to keep your your your tests your test results in it but also to write down questions jot down notes and and this can be a very valuable thing for you and have that with you at all times utilize your bat voicemail or your answering machine many of you have people who care about you and they they want to contact you they want to find out what’s happening but you know there are many times where you’re just not ready to talk to somebody or just have other things to do but you don’t want to alienate these people so use your voicemail you can always call them back later on don’t feel you have to take every call at every moment ask the family member or a friend to help you with the paperwork paperwork as you know whether it’s your insurer company whether it’s experimental clinical trial forms whatever these are can be very complicated have somebody help you with this and who is familiar with their condition and with what what is happening with you pay attention to your overall health diet and exercise I don’t think there’s anything that I would say is a standard diet or exercise regimen for somebody with a brain tumor but diet and exercise is something that’s important not only presumably the brain tumor but for for everybody everybody needs to pay attention to their diet and exercise if you have a brain tumor you want to watch your your

wife watch what you eat and again these are just standard things there’s not something special if you’re if you tend towards being overweight then you want how does he want to want to control what you’re eating exercise on a daily basis or as often as you can do it is just good common sense no matter what your condition walking if you can jogging whatever whatever works best for you but the idea is to keep active and stay active because I think the better the better shape that you’re in the better your immune system works the better your mind works the more clear you are and the better that you feel about yourself it’s important to set aside time for yourself sometimes things can be overwhelming making sure that you have a little time for yourself to collect your thoughts to to be available to think about things that you want to think in your own terms that’s important to do be patient I think you you have a sense that everything needs to be done immediately that you have sometimes unrealistic expectations about what’s going to occur allow yourself to be a little bit patient to to make sure that your anxiety doesn’t overwhelm everything else that you’re trying to do and the same token learn learn to relax be patient learn to relax you may need to allow yourself time to cry maybe time to feel sorry for yourself if you if you can compartmentalize that to a degree you and not make that dominate your your your feelings every day if you give yourself a little time to feel a little sorry or something to say okay I’m done with that I’m going to move on that gives you the best frame of mind or tackling the problems that are going to be ahead of you and additionally having a positive attitude with without restrictions and and you know I don’t I’ve been in the brain tumor field for for a couple of decades now I don’t have any great wisdom about why somebody gets a brain tumor or how that person has chosen usually it’s there’s nothing you could have done to prevent it there’s nothing you did wrong to get a brain tumor and it’s important to continue to live your life because you have a diagnosis of brain tumor and doesn’t mean that you can’t go to a movie or that you can’t have a a good meal or you can’t celebrate a birthday or do the things you’d like to do that’s that’s living that’s what everybody does every day and you you do that and until you’re not able to do that and it’s important to live your life because if you let the treatment of the of a brain tumor and the thoughts of a brain tumor close you down you you miss that out on the rest of your life nobody knows what the future is going to be and the idea is to live your life as fully as possible and until you can’t and I think that’s good advice where do you have a brain tumor whether you have heart disease or whether you’re perfectly healthy you you maximize your your the things you’d like to do and you continue to enjoy the journey in conclusion here let me say there are many benefits for brain tumor patients for enrolling clinical trial not only with the prospect of being able to have a better treatment but also because it allows you to just generally get better care it’s important to understand the risks the benefits and the other treatment options that you have now let me just finish by saying there’s never been a better time now for brain tumor patients that at any time in our history there are more new exciting things that are being developed every day there are more people working on brain tumor research now that any time in our history in fact probably and in the entire history of brain tumors combined there’s never been more people and for those of us who are in the field we have a lot of optimism for the future we’re excited about testing these new treatments and being able to provide some additional benefit for all of our brain tumor patients out there this concludes our didactic portion of the webinar and I think we are available for questions now presentation and certainly your incorporation of the quality of life element is very much appreciated and it’s a certainly an area that we as an organization get get a lot of questions from folks so we do have some time for questions now about ten minutes or so before we launch into the Q&A portion I did want to just take a couple quick minutes to mention a program called trial Connect which some of you may

already be familiar with trial Connect is a service that we offer here at the American brain tumor association that basically links brain tumor patients with appropriate clinical trials based on the patient’s tumor type and treatment history so earlier dr. Bruce mentioned clinical trials.gov and certainly that’s a place you can visit but trial Connect is a service that we have it’s free it’s confidential it’s offered in both English and Spanish if you’re interested in calling and speaking with a trial connect representative the phone number is eight seven seven seven six nine four eight three three or you can visit online and fill out your profile there the website address is WWE a trial connect it’s all one word Oh RG and you can learn more basically a single short secure questionnaire matches patients to enrollment criteria from all kinds of different brain tumor clinical trials and this dr. Bruce indicated there’s hundreds of them and then from that point patients will get connected to the right trial coordinators to see whether or not if a person is or could be eligible so I just wanted to put that out there the ABT a also offers a robust patient friendly brochure on clinical trials that as he said is available on our website and you’d be welcome and encouraged to check it out or if you’d like one mailed to you you can just send us an e-mail or give us a call so with that we can go ahead and start into some questions we did receive a few questions in advance so the first one i am i’d like to ask you dr. bruce is with respect to clinical trial payments i know you mentioned that already earlier in your presentation but often we get questions from patients wondering if they ever get reimbursement for their participation is that ever something that’s provided sometimes there is reimbursement but sometimes you can be reimbursed for your expenses such as if you have to travel to get additional tests sometimes that you can be reimbursed for your travel expenses occasionally but rarely may be paid simply for being on the clinical trial but most of the times these clinical trials not have very big budgets they don’t have a lot of money available so they try to to work on as close of a shoestring budget as possible but to answer your question there are times where you can be reimbursed for some of the outside expenses that that occur when you’re trying to join a clinical trial okay thank you the next question is typically how many clinical trials are necessary before a new treatment is approved well normally it’s really just phase one phase two and phase three so if if you if a new treatment progresses through the three phases of the trial and it’s shown to be effective and it’s approved so again phase one is the early stage where you start out of a small dose of the drug and keep increasing the dose until you begin to get a dose that causes side effects then phase two you take that particular dose of drug and give it to a large number of patients to see whether it seems to work or not and then the final trial is the phase three where you actually test that drug against best treatment available whatever what other other standard treatment would otherwise be done and see whether your drug is better than the best standard treatment then it’s then if it works it’s approved great thank you the next question is is a great one with respect to the compassionate care use that you mentioned a little earlier if there is a treatment that could be considered under compassionate use how do you get this underway how do you get the process started well probably the only person that that can do that is the person running that clinical trial that already has a particular drug available and can make some some of the enquiries I can tell you that it’s it can actually be very difficult and complicated to get compassionate use not saying that to discourage anybody who may be interested but as clinical trials and as the FDA have become more complicated more regulated it becomes more difficult to

get that compassionate use and I would say the two places to start or compassionate use or wherever your the doctor is that’s that’s making decisions about your brain tumor care and then secondly whoever is running the clinical trial with the particular drug that you’re interested in great thank you the next question asks if there are several tumor sites will the person still be considered for a clinical trial and then sort of the second part of the question is if the camasta key skills are increasing but not quite at 60% will they consider that an option there are many different types of clinical trials with different criteria for for who’s eligible so there are many clinical protocols where it’s limited to a person who has only one tumor but there are other clinical protocols out there that are open for people who have more than one tumor so normally it’s one or the other many many of the treatments are our designs or one or the other but to answer your question yes there aren’t treatments out there that are designed for people with more than one tumor in terms of the karnovski the karnovski score again most protocols usually require a minimum level of karnovski rating but there are exceptions to that there are many there are some quality of life protocols and there are some other treatment protocols that don’t have a minimum amount so whereas most trials who have a a minimum desired level of karnovski that’s not to say that all of them do thank you the next question is with respect to clinical trial active participation what happens if a patient wants to leave a trial in the middle of it either for medical reasons or just because they you know are no longer interested in participating any further are there any ramifications to that there there should not be this whole regulatory process the IRB the institutional review board the whole system of how clinical trials are conducted are designed so that there should be no penalty for you if at any time you decide to withdraw from the protocol and you know this is something obviously you should discussed with the investigator running the trial but ultimately there should be no penalty whatsoever for whatever reason that you have again we normally encourage people once they’re in a clinical trial to see it to the end but the the the the rights and protection is towards the patient so the patient can withdraw anytime they want for whatever reason they want thank you and we have time for just one more quick question before we need to wrap up for today on the last question is how are the final results of the trial made known how do people typically find out about that information for instance if they were participating yeah their clinical trials when all of the clinic went and clinical trial is completed the investigators and the scientists will collect all of the information based on all of the patients that were treated and normally what they do is they write it up or a scientific journal or to present it at a national meeting let’s say a a brain tumor investigational meeting or something of that sort so the results are normally put together and ultimately they are published and most scientific journals are those publications are available publicly for most of them so that’s really the final way but there can often be a very long lag time between when a clinical trial is finished and when the results actually get presented or published normally what you can do though is asked whether the lead investigator is on a clinical trial to keep you posted and they they may have anything from a newsletter to a website learning information or just informally sending you information on it furthermore if if you’re involved in a clinical trial normally you’re going to be going back for follow-ups so that best the Gators can begin to determine how well the treatment is is tolerated and how effective it’s been so I think if

you’re the formerly the published article we’ll come out at some point after the clinical trial but whoever is running the trial can keep you posted on what’s happening okay well thank you so much we’re looks like we’re finished with questions and we are going to go ahead and wrap up again dr. Jeffrey Bruce from the Columbia University brain tumor center thank you so much once again for helping to facilitate this understanding clinical trials webinar for us we really appreciate your expertise and taking the time out of your day to be with us thanks to all of you for joining us on your Saturday and we’ll hope to see you next time