Clinical trials for rare tumour types
Dr William Tap – Memorial Sloan-Kettering Cancer Center, New York, USA
Will, welcome to ecancer.tv. William, you’ve got a lot of hot topics here, I’m going to ask you quickly about each one of them. The TH302, now this is exploiting hypoxia finally, at last, and it’s pretty promising, is it?
I believe so. We know that chemotherapy has difficulty penetrating into tumours, into the hypoxic area. Most of the time chemotherapy can just penetrate into the perivascular areas where there’s a blood supply and normoxia. This drug, what happens is it actually diffuses into the hypoxic areas of tumours where it’s reduced into an alkylating agent, an iphosphoramide mustard type of agent and it’s very exciting. It needs to be given with chemotherapy so currently we are running a large phase III study in which TH302 is given with doxorubicin and it’s versus doxorubicin alone. It’s a collaborative effort with SARC, which is our large co-operative group and it’s going to be an international study.
So briefly describe the study, the clinical setting.
The clinical setting would be for patients that have high grade soft tissue sarcomas and they can enter into the trial. It’s an up-front study so no prior treatments for the disease and it’s randomised in a one to one fashion to either get TH302 plus doxorubicin versus doxorubicin alone. There are about 450 patients in the study, there’ll be about thirty centres in the United States, thirty centres in Europe, there will be centres in Israel and Russia and, through the NCIC, also a nice collaboration with Canada. We’re hoping to have about ten centres.
Well that’s for the future, we’ll eagerly await those results. You’ve got a phase II study of a CDK4 inhibitor in what’s called CDK4 amplified liposarcoma, what’s happening here?
That’s a trial that was run by Mark Dickson out of Memorial Sloan-Kettering and it stems from the fact that liposarcomas, which are cancers of fat, most of them, about 95%, have an amplification in CDK4 which helps modulate the cell cycle. The application of this drug is something that we’ve been eagerly waiting in liposarcoma and we ran a study at Memorial Sloan-Kettering with Dr Dickson and we looked at about thirty patients receiving this drug. Those results will be presented tomorrow at the sarcoma session and we’re seeing some very promising results. This is a rare tumour that we’ve needed treatment for for a long period of time and we’re hoping that this type of drug will change the biology of the liposarcoma and affect the course of disease in patients. From the results of this study we’re also in negotiations to see if we can have a larger phase III study to see in a larger population of patients will this drug help them.
Liposarcoma may not be very common but what might be the recommendations?
Liposarcoma is normally large tumours that can develop within the extremities or the abdomens and they are tumours of fat. There’s probably about several thousand cases diagnosed in the United States each year and surgery, right now, is the only conventional therapy we have for them. So the hope is that if we can do a larger study we may be able to gain an application of this drug in liposarcoma.
Now you’ve got another treatment for refractory soft tissue sarcoma using a monoclonal, cixutumumab, together with an mTOR inhibitor, temsirolimus.
Can you tell me what you’re getting on this?
Yes, so this is also another interesting study that was run out of a consortium that was started at Memorial Sloan-Kettering. There has been a lot of excitement, both with the use of mTOR inhibitors and IGF-1R inhibitors, they are inhibitors of the insulin growth factor pathway as single agents. This is a trial that actually looked at the combination and it looked at the combination in several cohorts, including cohorts of patients with soft tissue sarcoma and cohorts of patients with bone sarcoma. We actually screened the patients based on their IGF-1R status and tomorrow Dr Gary Schwartz, who led the trial for Memorial, will be presenting the data. The endpoint, the primary endpoint, which was to see if we could have progression free survival rates improving at twelve weeks was met in all cohorts.
What’s coming out of it for doctors then, potentially?
I think these are two agents, again, that we’re very much looking to apply in sarcomas. We are looking at the combination now in some of the sarcoma subtypes that we believe have tremendous efficacy that we’re pulling out of the trial. So we’re now in negotiations with other companies to see if we can move these drugs forward into larger phase III studies.
So what’s your feeling about some of this news, mainly your own I’m thinking of at the moment, here at ASCO, for busy cancer doctors? What do you recommend them to take home?
I think sarcomas are rare diseases so it’s very important that when they come across sarcomas that they work with some of the larger sarcoma centres in their area. They are also very heterogeneous diseases and we’ve seen over the past few years an explosion in the understanding of the genetic and the molecular abnormalities of these tumours. So now we have a lot of individualised treatments that we can offer patients. When I come to a meeting like ASCO I’m always amazed at the advances that we’re beginning to see. So for diseases that we thought we did not have treatments for a few years ago, we’re really beginning to see some of the new treatments evolve and I think the CDK4 inhibitor in liposarcoma is a perfect example of that.
Thank you very much.