Research in Primary Liver Cancer
Guest: Dr. Melanie Thomas – Hollings Cancer Center (HCC)
Host: Dr. Linda Austin – Psychiatry
Dr. Linda Austin: I’m Dr. Linda Austin. I’m interviewing Dr. Melanie Thomas who is Associate Professor of Medicine here at the Medical University of South Carolina and an expert in gastroenterology, in particular, in liver disease and liver cancer. Dr. Thomas, let’s talk, now, about the clinical trials that you are ready to get started. I understand there are two of them. What will those clinical trials be about?
Dr. Melanie Thomas: Two trials we’re getting ready to open in the next week or so are in liver cancer, primary liver cancer, which has a big name, hepatocellular cancer. That’s a cancer that starts in the liver, does not metastasize to the liver. It’s an uncommon disease but we do see patients with it here, at this institution. Patients with hepatitis B or C, or something that’s damaged their liver, can lead to that cancer. Most of those patients are not eligible for surgery or some other kind of therapy so they need chemotherapy. Currently, there is only one drug that is available for those patients. It’s called Sorafenib. So, there’s still a lot of room for improvement.
So, we have two very interesting trials opening. One is a randomized Phase II trial, which means there are two arms, and the patients will get randomized to one or the other.
Dr. Linda Austin: And by randomized, it means you flip a coin and they will get the investigational drug or they get placebo plus something else?
Dr. Melanie Thomas: That’s right, exactly. Randomized trials are really the gold standard for showing that something is better than something else. So, in this case, this is actually a fairly exciting trial because the new drugs I’ve been working on for about four years are being compared to Sorafenib, which I mentioned. This agent Sorafenib, which is oral, was approved by the FDA in late 2007. That was the first drug approved for primary liver cancer. It does prolong a patient’s survival over no treatment by a couple of months, but it has a fair number of side effects. And data that we have shows that we can actually do better than that.
The study arm is two drugs, one called bevacizumab (Avastin), which is an IV drug, and the other is called Tarceva, which is an oral drug. The combination, together, seems to be very potent in hepatocellular cancer. Both of those drugs are approved in other cancers, so they’re not truly investigational. They’re approved in colon, breast, lung and pancreas cancer, so they have a good track record.
The investigational arm is the Avastin and Tarceva. Patients will receive that arm or Sorafenib. So, they’ll be receiving the current standard of care or the two drugs to see if the results are better. MUSC is the lead institution, and the study will require about 120 patients, and there are five other sites around the U.S., the University of Miami, Wake Forest, University of Southern California, and UCSF, and there’s one other, M.D. Anderson. This is actually the first trial in the U.S. that is comparing something else to that standard of care.
Dr. Linda Austin: Now, in order to qualify for that study, a patient would have to have a primary diagnosis of hepatocellular carcinoma, correct?
Dr. Melanie Thomas: Correct.
Dr. Linda Austin: I’m sure that there are a lot of other criteria.
Dr. Melanie Thomas: Yes, there are. They can have other previous treatment, such as surgery or even radiation, but if their diseases progress, they can’t have had other previous chemotherapy. So, we call this a frontline trial. It’s the first line of systemic therapy. They have to have a pretty good performance status, in other words, be fairly active, taking care of themselves. The liver eligibility criteria are fairly liberal. The trial is designed for the kinds of patients that we see out in the community. In other words, they don’t have to have perfect liver function. Trials in many other diseases have to have perfect organ function in order to participate.
Dr. Linda Austin: And what is the second clinical trial you’re participating in?
Dr. Melanie Thomas: The second one is also in hepatocellular cancer. This is a trial, also, of an oral agent. Now, this is a second line study, so this is for patients who have already received Sorafenib and failed it, they’re disease grew or they didn’t tolerate it. So, it’s a second line trial, so there is no second line therapy in this disease. This one is also randomized and it’s a randomized Phase II, but it is placebo-controlled. That’s what patients are often asking, well, am I going to get the drug or am I going to get placebo? So, this trial is different in that, yes, it’s placebo-controlled, and it’s blinded. The doctor or the patient will not know which they’re receiving. And, again, in placebo-controlled, there is no standard second line therapy, so there’s nothing to control, to compare it to. So, placebo is really the scientifically sound comparator.
Dr. Linda Austin: Liver cancer really, as you describe how few treatments there are, is at the forefront in an area where there’s a lot of work still to be done. It’s not like some other forms of cancer where there are already very well established, good, therapeutic agents like, say, testicular carcinoma.
Dr. Melanie Thomas: Or breast cancer. Yes. Part of why I’m interested in liver cancer is I find the GI tract and liver very interesting, but also because it is what we term an orphan disease, or an orphan tumor. There’s been so much attention on the cancers that have lots of patients, and that makes sense, you know, breast, lung, colon, prostrate. There are a lot of people affected by those. But I felt, five or six years ago, starting out, that the liver cancer patients were sort of a forgotten group and I didn’t like that, so that’s why I started to focus on this. I felt as though there should not be a cancer for which there’s no therapy.
Dr. Linda Austin: Since a lot of people who may have just had a loved one get this diagnosis may not have medical background, it’s confusing because so often cancers that start somewhere else, like the lung or the breast, will spread or metastasize to the liver, and it’s not that kind of liver cancer, that’s so-called secondary. You’re talking about cancer that starts in the liver.
Dr. Melanie Thomas: That’s right. That is a very common easily confused distinction. So, yes, it’s not for cancers that have spread to the liver. It’s for one type of cancer that starts in the liver. It can go other places but, generally, it’s in the liver.
Dr. Linda Austin: How long do you anticipate this study will go on for? How many subjects are you looking for?
Dr. Melanie Thomas: The frontline, the randomized with the two drugs versus one, 120 patients. We would like to accrue it in about 18 months, and sooner than that if we can. There’s a lot of interest in this trial. At M.D. Anderson, where I was previously, we did a single arm Phase II exploratory study of 40 patients with the Avastin and Tarceva and really saw some very impressive results. Just to give you an idea, the drug Sorafenib was approved by the FDA because it improved survival. For a patient who has primary liver cancer in which there’s no other treatment, such as surgery or radiation, or something enteropathic, their average life expectancy is around seven months, between six to eight months. So, it’s a very bad disease. With Sorafenib, the average survival is about 10 and half months, which doesn’t seem like a lot but that was, statistically, a meaningful improvement over that six to eight.
So, in our trial of 40 patients, and then, actually, 60 patients, the median survival is closer to 15 months. Now, it’s small, and you really can’t compare 60 patients to 600, but that’s why we’re doing this study, to, in the same set of patients, really see how the Avastin and Tarceva stack up to the Sorafenib.
Dr. Linda Austin: And, of course, I think, when people hear those scary statistics, when you average, it’s important to remember that half of the people actually do better than that, will live longer than that, and there may be someone who lives a good bit longer than that out there.
Dr. Melanie Thomas: Yes, absolutely. And in liver cancer, I always tell patients when they ask for that statistic, the first thing I say is, averages don’t apply to you. You’re an individual. They’re just numbers from studies. So, try not to focus on that. But, in liver cancer, in particular, there’s a very broad spread. There are patients who are very sick, mostly from an underlying bad liver disease. That’s part of why this cancer is such a challenge, because it’s a cancer inside a liver that’s, in many cases, very damaged.
Dr. Linda Austin: To begin with.
Dr. Melanie Thomas: To begin with. In certain circumstances, this cancer arises in an otherwise not damaged liver; we can’t find any reason why it developed. But that’s a very small minority. So, most patients, again, have something that has caused underlying liver damage, alcohol, hepatitis B, hepatitis C. Now, something called fatty liver, which is just becoming, I wouldn’t say epidemic, that would probably be overstating it, but with the obesity rate in the United States, we are seeing more and more fatty liver disease, which can lead to cancers and liver failure, and a lot of problems. So, that average, again, is just an average. There are many patients who live substantially longer than that. That’s a good thing.
Dr. Linda Austin: Dr. Thomas, thanks so much for talking with us today.
Dr. Melanie Thomas: Thank you.
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