A clinical trial is a study designed to evaluate a promising new medical treatment. It includes research done to evaluate new ways to prevent and diagnose and/or treat cancer. At Roswell Park Comprehensive Cancer Center, up to 50% of our patients are eligible to enter clinical trials. Many types of treatment can be tested including: new ways of preventing cancer such as drugs, diet, and/or exercise: new drugs to treat cancer and new ways to use existing treatment such as surgery or radiation therapy.
Many people worry that if they enroll in a clinical trial, they may not get the best treatment, and they wonder if they might end up with the placebo treatment that won't treat their cancer.
When clinical trials identify new and effective treatments, these treatments will eventually become the new standard of care that will be offered to future patients. Today's standard treatments were researched and proven by clinical trials done in the past.
In this segment, Igor Puzanov, MD, discusses what you can expect if you are considering enrolling in a clinical trial.
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What to Expect: Participating in a Clinical Trial
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Learn more about Igor Puzanov, MD
Igor Puzanov, MD
Igor Puzanov, MD is a Clinical Professor of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Professor of Medicine and Director of Early Phase Clinical Trials Program in the Department of Medicine at Roswell Park Comprehensive Cancer Center.Learn more about Igor Puzanov, MD
Transcription:
What to Expect: Participating in a Clinical Trial
Bill Klaproth (Host): Volunteers in clinical trials help doctors find new ways to improve treatments, develop cures, and increase the quality of life for patients. So is volunteering in a clinical trial right for you, and what to expect when you’re participating in a clinical trial. Here with us, is Dr. Igor Puzanov, director of the Early Phase Clinical Trials Program and chief of Melanoma at Roswell Park Comprehensive Cancer Center. Dr. Puzanov, thank you for your time today. What types of clinical trials are there?
Dr. Igor Puzanov (Guest): Thank you, very much, for having me. It’s a real pleasure to talk to you and hopefully to patients. There are different types of clinical trials, and we will be talking about all of them today. When you first develop a new potential drug for patients it’s been developed in the lab preclinically, meaning it’s usually developed by putting the drug on the cancer cells in the petri dish or you are injecting cancer cells into mice, and then you give them the drug, and then you are using other animal models. At some point, you are satisfied that you have a drug which is potentially useful, that there was activity in these laboratory models, and that the toxicity profile of the drug was acceptable to actually take it forward to patients.
You will now be entering the first type of trial, which is usually called Phase One, or Phase Zero even – there are some specialized Phase Zero trials. The Phase One trial, or Phase Zero trials, like Phase One, is really a trial to look at how the drug behaves in the patient. You hope, of course, that it will have an effect on the patient’s cancer, but you cannot make that promise. You haven’t treated any patients when you start and only a limited number when you are going forward with ten, twenty patients, trying to change the dose, and change schedules, looking at how the drug gets into patient’s bodies, how it leaves, and even more importantly how it may affect the tumors and the specific targets which you specify for the drug, so it’s very experimental.
On the other hand, historically, only about 5% of patients responded on a Phase One clinical trial, but of course, 5% is better than zero. Recently, with new drugs and new combinations, the number actually may be as high as 25 or even 30% in some cases. I would never promise a cure or a treatment effect from the Phase One trial -- actually in real life; there is a substantial number of patients with the new drugs which are having benefits basically from the gate – from the very early trails.
That’s your Phase One, and the outcome basically means that you develop the dosing, you develop the levels, you develop the schedules – how to do things. You develop some biomarkers, some scans, how to evaluate the drug effects, and you are ready to move to the Phase Two trials and then Phase Three trials, which, of course, are now more mature. You know more about the drug – hopefully, the type of patient which may benefit from it, and now you are giving it to more patients, again, looking at the toxicity, any unusual side-effects, anything you may have missed in these early trials. You are moving to multiple tumor types, developing biomarkers, and at some point, you have enough data to either go directly to the FDA and ask for what we call accelerated approval, meaning -- look, it’s very, very good. We should get approval to actually give it to everybody in the US. And of course, they sometimes do, and they still want confirmatory, bigger trials.
Or if that is not a good way to go forward – it’s not possible, then you simply have to move to a Phase Three trial, which now is usually randomized. The previous ones are not usually randomized; they are just like – one drug is given to everybody. The Phase Three is randomized, and patients will now be randomized to either golden standard of care, which is what you would give them anyway, or the new drug – or a new combination including a new drug, hoping that actually the new combination or the drug will be better than your gold standard. That, of course, takes a much longer time, but at the end, if it’s positive, usually forms a basis for a permanent approval of the drug after which the drug is available to anybody in the clinic. That’s how the drugs are developed. There are some new paradigms coming, but in general, this is how every drug – patients are now usually given – every drug has to go through Phase One, Phase Two, and Phase Three testing, and have to pass all of these, and at the end was found to be beneficial and useful.
Bill: Well, thanks for explaining the different phases to us. These clinical trials truly are as the saying goes, where the rubber meets the road. It really is important, and it’s where you really start the evaluation process of a certain drug. Do people stay on through stage one through three, generally? Or do you have a new group of people at each stage?
Dr. Puzanov: We usually have a new group of people at each stage as the inclusion/exclusion criteria -- i.e. what type of patient should enter the trial, may change. For example, a Phase One trial, these will typically, but not always be patients who already had several lines of treatment. They are a little bit running out of options and so going with a little bit riskier treatment opportunity may be actually more beneficial or more applicable or more appropriate. Usually, when you get to the Phase Three testing, a lot of times you are looking for patients who have never been treated with any drugs and you are now testing the drugs in those patients, so it may change.
I can tell you, with more active drugs, we actually see a lot of patients who are on a Phase One clinical trial, let’s say with Check Point Inhibitors, who actually still are getting these drugs, or still are benefitting from cancer being in submission 10, 15 years later now with drugs such as Yervoy or Opdivo. From that standpoint, you see the same patient – the same patient who was actually helped by the drug on a clinical trial.
Bill: Right, and what are the risks versus benefits of participating in a clinical trial?
Dr. Puzanov: The risks and benefits will always be a little different depending on the mechanism of action of the drug – the mode of how it’s given, but clearly every clinical research has to be well-planned. It has to be scientifically valid, so that’s why we actually take every protocol through our scientific review committee to make sure that what is proposed is scientifically valid.
Number two, after the science has been evaluated, it’s taken to the institutional review board – the ethics commission, basically looking at whether it’s planned properly, that patients will be treated equally, that there will be good patient protection from any harm, that actually the risks will be well-laid out so patients may make really informed decisions whether they want or not want to participate.
These are important checks and balances on any research, and also, as I always stress to any patients, patients may go on a clinical – doesn’t have to -- and even when you actually decide to go on a clinical trial, sign a consent form, go through the screen and make sure that all of the inclusion criteria are fulfilled, that you don’t possess any of these exclusion criteria and you start your treatment, even – for any reason patients can decide to stop anytime. The patient is in the driver seat, and we are working with the patient, not own the patient. It’s a partnership, and there’s a lot of mutual trust that has to be given and taken. It’s very important not to take that trust lightly.
Bill: Right, and Dr. Puzanov, who can qualify, and where should people look to find available trials?
Dr. Puzanov: The best way to look for clinical trials may be to look locally at your NCI-designated cancer center, such as – we in Buffalo, at Roswell Park Cancer Institute, are one of the 43 NCI-designated comprehensive cancer centers -- because those centers usually have a very robust pipeline of new drugs in development in various stages one, two, three. Alternatively, one can look actually at web pages for particular diseases. A lot of patient advocacy groups like lung cancer patients, ovarian cancer patients, renal cancer patients, will actually have online bulletins where they have information about trials for their particular disease. I treat patients with melanoma in the Melanoma Research Foundation.
Then, actually, one of the most comprehensive ways is to go to ClinicalTrials.gov web page, which is a registration of all different clinical trials, and simply type in the type of cancer I have – melanoma, for example, brain cancer – then I will say Phase One, or Phase Two, or Phase Three, or I may even ask a specific type of drug, and the search engine will actually give me all the trials available and also places where these trials are being conducted. There are multiple ways, but a local oncologist would be able to help guide the patient and try to help them navigate the information. But I think really the trusted resources would be the NCI-designated cancer institute closer to the patient’s home because a lot of the patients may not be able to travel long distances on a regular basis.
Bill: Well, that’s really good information, and thank you, so much, for sharing that with us, Dr. Puzanov. And thanks for your time, today, in talking about clinical trials. For more information, visit RoswellPark.org, that’s RoswellPark.org. You’re listening to Cancer Talk with Roswell Park Comprehensive Cancer Center. I’m Bill Klaproth. Thanks for listening.
What to Expect: Participating in a Clinical Trial
Bill Klaproth (Host): Volunteers in clinical trials help doctors find new ways to improve treatments, develop cures, and increase the quality of life for patients. So is volunteering in a clinical trial right for you, and what to expect when you’re participating in a clinical trial. Here with us, is Dr. Igor Puzanov, director of the Early Phase Clinical Trials Program and chief of Melanoma at Roswell Park Comprehensive Cancer Center. Dr. Puzanov, thank you for your time today. What types of clinical trials are there?
Dr. Igor Puzanov (Guest): Thank you, very much, for having me. It’s a real pleasure to talk to you and hopefully to patients. There are different types of clinical trials, and we will be talking about all of them today. When you first develop a new potential drug for patients it’s been developed in the lab preclinically, meaning it’s usually developed by putting the drug on the cancer cells in the petri dish or you are injecting cancer cells into mice, and then you give them the drug, and then you are using other animal models. At some point, you are satisfied that you have a drug which is potentially useful, that there was activity in these laboratory models, and that the toxicity profile of the drug was acceptable to actually take it forward to patients.
You will now be entering the first type of trial, which is usually called Phase One, or Phase Zero even – there are some specialized Phase Zero trials. The Phase One trial, or Phase Zero trials, like Phase One, is really a trial to look at how the drug behaves in the patient. You hope, of course, that it will have an effect on the patient’s cancer, but you cannot make that promise. You haven’t treated any patients when you start and only a limited number when you are going forward with ten, twenty patients, trying to change the dose, and change schedules, looking at how the drug gets into patient’s bodies, how it leaves, and even more importantly how it may affect the tumors and the specific targets which you specify for the drug, so it’s very experimental.
On the other hand, historically, only about 5% of patients responded on a Phase One clinical trial, but of course, 5% is better than zero. Recently, with new drugs and new combinations, the number actually may be as high as 25 or even 30% in some cases. I would never promise a cure or a treatment effect from the Phase One trial -- actually in real life; there is a substantial number of patients with the new drugs which are having benefits basically from the gate – from the very early trails.
That’s your Phase One, and the outcome basically means that you develop the dosing, you develop the levels, you develop the schedules – how to do things. You develop some biomarkers, some scans, how to evaluate the drug effects, and you are ready to move to the Phase Two trials and then Phase Three trials, which, of course, are now more mature. You know more about the drug – hopefully, the type of patient which may benefit from it, and now you are giving it to more patients, again, looking at the toxicity, any unusual side-effects, anything you may have missed in these early trials. You are moving to multiple tumor types, developing biomarkers, and at some point, you have enough data to either go directly to the FDA and ask for what we call accelerated approval, meaning -- look, it’s very, very good. We should get approval to actually give it to everybody in the US. And of course, they sometimes do, and they still want confirmatory, bigger trials.
Or if that is not a good way to go forward – it’s not possible, then you simply have to move to a Phase Three trial, which now is usually randomized. The previous ones are not usually randomized; they are just like – one drug is given to everybody. The Phase Three is randomized, and patients will now be randomized to either golden standard of care, which is what you would give them anyway, or the new drug – or a new combination including a new drug, hoping that actually the new combination or the drug will be better than your gold standard. That, of course, takes a much longer time, but at the end, if it’s positive, usually forms a basis for a permanent approval of the drug after which the drug is available to anybody in the clinic. That’s how the drugs are developed. There are some new paradigms coming, but in general, this is how every drug – patients are now usually given – every drug has to go through Phase One, Phase Two, and Phase Three testing, and have to pass all of these, and at the end was found to be beneficial and useful.
Bill: Well, thanks for explaining the different phases to us. These clinical trials truly are as the saying goes, where the rubber meets the road. It really is important, and it’s where you really start the evaluation process of a certain drug. Do people stay on through stage one through three, generally? Or do you have a new group of people at each stage?
Dr. Puzanov: We usually have a new group of people at each stage as the inclusion/exclusion criteria -- i.e. what type of patient should enter the trial, may change. For example, a Phase One trial, these will typically, but not always be patients who already had several lines of treatment. They are a little bit running out of options and so going with a little bit riskier treatment opportunity may be actually more beneficial or more applicable or more appropriate. Usually, when you get to the Phase Three testing, a lot of times you are looking for patients who have never been treated with any drugs and you are now testing the drugs in those patients, so it may change.
I can tell you, with more active drugs, we actually see a lot of patients who are on a Phase One clinical trial, let’s say with Check Point Inhibitors, who actually still are getting these drugs, or still are benefitting from cancer being in submission 10, 15 years later now with drugs such as Yervoy or Opdivo. From that standpoint, you see the same patient – the same patient who was actually helped by the drug on a clinical trial.
Bill: Right, and what are the risks versus benefits of participating in a clinical trial?
Dr. Puzanov: The risks and benefits will always be a little different depending on the mechanism of action of the drug – the mode of how it’s given, but clearly every clinical research has to be well-planned. It has to be scientifically valid, so that’s why we actually take every protocol through our scientific review committee to make sure that what is proposed is scientifically valid.
Number two, after the science has been evaluated, it’s taken to the institutional review board – the ethics commission, basically looking at whether it’s planned properly, that patients will be treated equally, that there will be good patient protection from any harm, that actually the risks will be well-laid out so patients may make really informed decisions whether they want or not want to participate.
These are important checks and balances on any research, and also, as I always stress to any patients, patients may go on a clinical – doesn’t have to -- and even when you actually decide to go on a clinical trial, sign a consent form, go through the screen and make sure that all of the inclusion criteria are fulfilled, that you don’t possess any of these exclusion criteria and you start your treatment, even – for any reason patients can decide to stop anytime. The patient is in the driver seat, and we are working with the patient, not own the patient. It’s a partnership, and there’s a lot of mutual trust that has to be given and taken. It’s very important not to take that trust lightly.
Bill: Right, and Dr. Puzanov, who can qualify, and where should people look to find available trials?
Dr. Puzanov: The best way to look for clinical trials may be to look locally at your NCI-designated cancer center, such as – we in Buffalo, at Roswell Park Cancer Institute, are one of the 43 NCI-designated comprehensive cancer centers -- because those centers usually have a very robust pipeline of new drugs in development in various stages one, two, three. Alternatively, one can look actually at web pages for particular diseases. A lot of patient advocacy groups like lung cancer patients, ovarian cancer patients, renal cancer patients, will actually have online bulletins where they have information about trials for their particular disease. I treat patients with melanoma in the Melanoma Research Foundation.
Then, actually, one of the most comprehensive ways is to go to ClinicalTrials.gov web page, which is a registration of all different clinical trials, and simply type in the type of cancer I have – melanoma, for example, brain cancer – then I will say Phase One, or Phase Two, or Phase Three, or I may even ask a specific type of drug, and the search engine will actually give me all the trials available and also places where these trials are being conducted. There are multiple ways, but a local oncologist would be able to help guide the patient and try to help them navigate the information. But I think really the trusted resources would be the NCI-designated cancer institute closer to the patient’s home because a lot of the patients may not be able to travel long distances on a regular basis.
Bill: Well, that’s really good information, and thank you, so much, for sharing that with us, Dr. Puzanov. And thanks for your time, today, in talking about clinical trials. For more information, visit RoswellPark.org, that’s RoswellPark.org. You’re listening to Cancer Talk with Roswell Park Comprehensive Cancer Center. I’m Bill Klaproth. Thanks for listening.