Transcript

My name is Dr Gentry King. I am one of the GI medical oncologists here at Seattle Cancer Care Alliance. I am an assistant professor at the University of Washington and the Fred Hutchinson Cancer Research Center.

I am going to be talking about one of the trials that we have in progress that was recently presented at ASCO GI this past week. It is a feasibility study of a multiomic platform-based testing in patients with localized and resectable biliary tract cancers.

This testing platform includes the generation of tissue organoids, and also a serial monitoring of circulating tumor DNA in both the perioperative space, which means that we get a sample before and after an operation, and also throughout adjuvant chemotherapy.

As a way of background, biliary tract cancers, as we know, are an uncommon/rare subtype of cancers. They are composed of a heterogeneous group of cancers, namely gallbladder cancer, and bile duct cancer, otherwise known as cholangiocarcinoma.

Cholangiocarcinomas are anatomically and biologically different within themselves. There is an intrahepatic cholangiocarcinoma, a perihilar cholangiocarcinoma, and a distal extrahepatic cholangiocarcinoma.

When someone has a localized biliary tract cancer, the treatments and the only shot that a patient has for cure would be to completely resect or remove the tumor from the body. Thereafter, however, there is a high likelihood that these cancers come back without doing any chemotherapy thereafter.

In treating these cancers, when someone gets a resection, typically, we recommend what we call adjuvant chemotherapy. Adjuvant chemotherapy for biliary tract cancers consist of a pill called capecitabine. This is typically given for six months.

There is a situation, however, that is somewhat peculiar. When these cancers are removed, there is no evidence that we can see of cancer in there. When we are giving adjuvant treatment, we do not have a barometer to figure out if chemotherapy is working or not.

This poses a challenge. This is one of the challenges that we hope to address with this study. This study involves taking the resected tumor sample and creating organoids out from that tumor sample. Organoids are a mini cancer in a petri dish that we can run high throughput drug testing. We are hoping to get some insights onto the tumor biology from these organoids.

Hopefully, we can also get more insight on the sensitivity and relative resistance of some of the chemotherapy agents that we use for these cancers, and also some of the targeted therapies that we use for these cancers.

The other aspect of this study is to do what we call serial circulating tumor DNA testing. Circulating tumor DNA testing is an emerging strategy that is able to detect very low levels of residual cancer in patients who had a resection.

This is a strategy that is already in use in colon cancer. It is a very powerful tool that still needs to be developed further in other cancers, like biliary tract cancers. We are hoping to evaluate the kinetics and the dynamics of the presence of circulating tumor DNA before an operation, after an operation, and also, throughout patients getting adjuvant chemotherapy.

Circulating tumor DNA has the potential to be a very sensitive tumor marker. Although we have tumor markers today that we use for bile duct cancers like CA 19-9 and CEA, they are not very sensitive, nor are they very specific.

We are hoping that circulating tumor DNA can be a test that is more sensitive and specific and can help guide clinicians and researchers in developing treatment strategies for patients with resected bile duct cancers.

Bile duct cancers and gallbladder cancers are not common. There are in some series called rare cancers. Doing adjuvant clinical trials for these cancers in this setting is difficult. In fact, the clinical trial that got capecitabine approved took about 10 years in many different cancer centers.

That is a barrier to moving the needle forward with regards to developing therapeutic strategies in the adjuvant setting for these cancers. We are hoping that with the data that we are potentially going to be obtaining from this study, that the data can inform the developments and the design of rational clinical trials.

Typically, with adjuvant clinical trials, the endpoint is usually overall survival, in which we would need to wait many years for that endpoint to result. There is emerging data that the clearance of circulating tumor DNA from a patient who has a positive level of circulating tumor DNA can be one of those surrogate markers.

If that pans out to be the case in biliary tract cancers, that would certainly accelerate and move the development of therapeutic strategies forward in this very difficult to treat and rare cancer. For this study, we aim to accrue 15 patients for the feasibility and to get preliminary data.

Although these cancers are rare, our center here at the University of Washington has done a great job accruing to the study. We are halfway. So far, this has been a feasible strategy. Mind you that the circulating tumor DNA is actually a clinically-available test.

The organoid generation is not, but we are obtaining some interesting data from organoid drug testing. We are hoping that the study will be completed in the next six to eight months. We look forward to publishing our results then.