Chapter 11: Creating Networks for Clinical Trials

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Chapter 11: Creating Networks for Clinical Trials

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Dr. Yung begins this chapter by observing that, in 1988, the new Department had expanded and Dr. Field was ready to retire. Dr. LeMaistre wanted to expand neuro services and recruited Dr. Leaven to chair Neuro-Oncology and provided him with a large package to expand the research and clinical operations. Dr. Yung notes that he was still continuing to run his own research. He also took advantage of the NCI's desire to stimulate brain tumor research and he created a network of institutions for running Phase I clinical trials. He describes what he did to create the consortia under NCI guidelines and the lessons learned as the networks were reorganized. Dr. Yung observes that this project resulted in the NCI adding pediatric brain tumors to clinical trials. He explains that brain tumors are the second most common cancers in children. He also provides an overview of the limited array of drugs available for treating brain cancers, with focus now moving from cytotoxic agents to targeted therapies and immunotherapies. He notes that as the Department grew, there were more opportunities to take advantage of patient philanthropy to support research.

Identifier

Chapter 11: Creating Networks for Clinical Trials

Publication Date

6-18-2014

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; Contributions; Activities Outside Institution; Building/Transforming the Institution; Multi-disciplinary Approaches; Discovery and Success; Overview; Definitions, Explanations, Translations; Understanding Cancer, the History of Science, Cancer Research

Transcript

Wai-Kwan Alfred Yung, MD:

Oh yeah because --- so --- so by 1988 --- by 1988 we have --- Oh I don’t even know how many faculty we have. We have several fellows that we trained and --- and stayed with us. But in 1988, you know, Dr. --- Dr. Field was ready to retire and so the --- then Dr. LeMaistre decided to again expand the --- the Neuro-Oncology Group and at that same time Neurosurgery.

Tacey Ann Rosolowski, PhD:

Hmm.

Wai-Kwan Alfred Yung, MD:

You know. Th --- So the --- So the first ex --- the first expanded because Dr. Field retired. So we launch a --- a national search for a Chairman to replace Dr. Field and the search, you know, resulted in recruiting Dr. Victor Levin from UCSF to --- to join the Department of Neuro-Oncology. And --- And he was given a very big package of expanding the program. Both in the research side as well as the clinical side. Tacey Ann Rosolowski Okay. Yeah, how big was that package? I mean do you know the details of it?

Wai-Kwan Alfred Yung, MD:

Oh, I --- I think that it was big because w --- he was given a lot of laboratory space to increase the laboratory presence with, you know --- we --- we --- with I think we --- he brought in two scientists right away and wi --- together with Peter. And then we also recruited another one in the fall. So --- So it’s a big expansion

Tacey Ann Rosolowski, PhD:

Another big expansion.

Wai-Kwan Alfred Yung, MD:

on --- on the laboratory side.

Tacey Ann Rosolowski, PhD:

Right.

Wai-Kwan Alfred Yung, MD:

And then w --- we also give him a few more clinical faculty because we need to expand our faculty side on Neurology as well as Brain Tumor.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

You know, I remain as a Deputy to --- to Victor to --- to really --- I mean he put a lot of focus on --- on --- on the research side and put development with Neurosurgery. And I helped more on --- more the --- the nitty-gritty of developing clinical trial for brain tumor. You know, managing the Neurology Consult Service. You know, doing more of the --- on the --- on this, you know, clinical administration side.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

And cont --- An --- And continued to run my own research because at that time I o --- I ha --- not only I have a IO-1 for my laboratory, I also have a grant to run --- to run a clinical network focusing on Phase 1, Phase 2 trial for brain tumor. There’s a --- NCI created several network in the --- in the late ‘80’s and we --- we completed and I --- I was PI for one of the grant to develop a network of --- of four instuti --- three or four institutions. Tacey Ann Rosolowski Now what was the significance of --- of doing that? What was the aim of doing that?

Wai-Kwan Alfred Yung, MD:

The --- Well the aim is --- is, you know, finding b --- there is no --- there is no --- number one there is no attention paid to brain tumor --- malignant brain tumor treatment other than radiation therapy and surgery.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

Chemotherapy is in a --- really infancy of development. And --- And this is a --- this is a very tough disease.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

So we --- we --- we want to really gain more research. Not only in the laboratory but also in the clinic. And the opportunity came when NCI is willing to increase our funding to create network of _____ () institutions to start some more clinical trial in brain tumors --- specifically in brain tumor. And --- And using the network to --- to really develop, you know, leads and --- and early signals to ____ ( And that is a major --- I mean --- is --- is really a major stimulus to the Clinic Research Committee for brain tumor among the neurologists and neurosurgeons. We --- I --- That is a very important milestone in terms of clinical research for malignant brain tumor for NCI to create these a --- a --- specific brain tumor consortium. You know, because brain tumor is not getting a whole lot of attention in the big cooperative group at that time, you know.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

--- with the group, you know. Tacey Ann Rosolowski So tell me --- I mean since this was so important --- I mean tell me how --- tell me how this worked at the time. So what did you do to help make this happen?

Wai-Kwan Alfred Yung, MD:

The --- The, you know, so-called research --- request for application. You know, I --- because, you know, --- CTEP at that time working some consultation with --- with the different groups say well it will be --- it will be, you know, great and necessary if you want to stimulate more research in the brain tumor area is to create, you know, network that can focus on early stage trial of brain tumor using the NCI drug. So at that time they decid --- NCI decided to fund three small groups. They ask people to create three small groups. These small groups called consortium. Each group could have up to five centers in them. And --- And so we --- so --- so the comu --- so the --- the --- the --- the --- the group of research of center decided to --- so we all talk and then we --- somehow we gravitate into three group of people. I de --- I, you know, develop a group together with --- with D -- -Dr. Fine (Feun?) (0) and Dana Farber. And then we have Dr. Fine, Dana Farber what do we --- who else did we have --- I think kind of --- kind of little break in the --- in the number. So I organize a group with three centers

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

and there is a fellow called Stuart Grossman at Hopkins, he crea --- he develop with another five centers and UCSF --- I think UCSF had ano --- also created a group with five centers. So these five centers form a --- what we call collaborative consortium. We will, you know, construct clinical trials together

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

with --- with NCI’s drug --- the --- the --- they have NCI --- working with --- with NCI to develop drug that they give us to develop trial

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

And NCI give us funding to manage the data, to develop the protocol, and enter patient into the trial, you know. So there are three network.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

Yeah. And after the first four years we, you know --- NCI decided that, you know, probably be better to consolidate the strength.

Tacey Ann Rosolowski, PhD:

Huh.

Wai-Kwan Alfred Yung, MD:

So we --- we take the center of the three network and --- and group into two networks. So the next phase of funding is go from three network into two network. So w --- I, you know, as the PI of my network I merged my network with the UCSF network.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

You know. Tacey Ann Rosolowski What did you --- What did you learn from that process? I mean, it sounds like a pretty amazing thing to get all these people working together.

Wai-Kwan Alfred Yung, MD:

Well we learn how to get people work together.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

We --- We --- We also learn to really, you know, sort of divide up some of the emphasis among the three groups. And we learn how to run trial together.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

We also learn, you know, really establish better relationship with --- with NCI to be able to really, you know, get actually more NCI attention not only in the clinical side, also in the research side and say hey we could not do cl --- clinical research because we don’t have enough basic science research in this area . Tacey Ann Rosolowski How interesting.

Wai-Kwan Alfred Yung, MD:

_____ (0 Tacey Ann Rosolowski So it really revealed some gaps

Wai-Kwan Alfred Yung, MD:

So we revealed some gap, you know. And so it --- it actually increased a lot of attention from, you know, --- from the NCI side. So much so that actually NCI also create a network for childhood brain tumor.

Tacey Ann Rosolowski, PhD:

Oh wow.

Wai-Kwan Alfred Yung, MD:

Beside the three adult network.

Tacey Ann Rosolowski, PhD:

Huh.

Wai-Kwan Alfred Yung, MD:

La --- Later on they also fund a pediatric brain tumor network.

Tacey Ann Rosolowski, PhD:

Hmm.

Wai-Kwan Alfred Yung, MD:

You know. Tacey Ann Rosolowski I hadn’t --- I mean, you know --- stupidly I hadn’t even thought of that. I mean I was interviewing Eugenie Kleinerman [Oral History Interview] this morning

Wai-Kwan Alfred Yung, MD:

Uh-huh

Tacey Ann Rosolowski, PhD:

who of course talks a lot about how Pediatrics is often not thought about in clinical trials and of course this would be an area particularly in rare cancers.

Wai-Kwan Alfred Yung, MD:

Yeah. So --- So we --- So we actually through the --- the --- the development of three adult consortium --- so NCI also later on they --- oh we need to have a pediatric consortium

Tacey Ann Rosolowski, PhD:

Pediatric. Yeah.

Wai-Kwan Alfred Yung, MD:

to --- to stimulate pediatric. Because pediatric brain tu --- tu --- brain tumor in children is a second cancer. Tacey Ann Rosolowski What do --- What do you mean?

Wai-Kwan Alfred Yung, MD:

The most common cancer in

Tacey Ann Rosolowski, PhD:

Oh.

Wai-Kwan Alfred Yung, MD:

children is leukemia.

Tacey Ann Rosolowski, PhD:

Right.

Wai-Kwan Alfred Yung, MD:

And the mo --- And the second most common cancer in children is brain tumor.

Tacey Ann Rosolowski, PhD:

I had no idea.

Wai-Kwan Alfred Yung, MD:

Yeah.

Tacey Ann Rosolowski, PhD:

Wow.

Wai-Kwan Alfred Yung, MD:

Yeah because you look at pediatric cancer, leukemia and lymphoma but it’s actually more leukemia than --- leukemia is number one. Among the solid tumor, brain tumor is. So right now brain tumor is probably the number one --- number one cancer killer in children. Because leukemia treatment is --- is --- has so --- has made so much advance. Tacey Ann Rosolowski Wow. I had no idea.

Wai-Kwan Alfred Yung, MD:

Yeah.

Tacey Ann Rosolowski, PhD:

That’s really something. Huh. So, I mean, just --- just for the record what were some of the drugs that you were testing during this time? I mean, if you can recall.

Wai-Kwan Alfred Yung, MD:

Yeah. We would --- that’s --- that is also one of the issue we have, you know. We actually don’t have very good drug

Tacey Ann Rosolowski, PhD:

Oh, I see.

Wai-Kwan Alfred Yung, MD:

for brain tumor. Most of our trial has been --- has been, you know --- had not been very successful. I mean, we basically test almost all the drugs that we use in --- in solid tumor. Cis-platinium, methotrexate, 5-FU, CCNU, BCNU, you name it. All the cancer --- All the --- All the, you know, chemotherapy drug that is available for solid tumor we tested in --- in glioblastoma. Tacey Ann Rosolowski Uh-huh. Back in the ‘80s.

Wai-Kwan Alfred Yung, MD:

Back in the ‘80s and ‘90s. Uh-huh. You know, nothing really come up better than BCNU and CCNU which is approved for specific for brain tumor. And that was the main drug for --- from the ‘80s to the ‘90s until temozolomide came along in 1995, you know. And that was the second, you know, active drug, which is strictly speaking, not that much better than BCNU or CCNU.

Tacey Ann Rosolowski, PhD:

Oh. Wow.

Wai-Kwan Alfred Yung, MD:

You know, so brain tumor research follow cancer research at large. You know, we move from cytotoxic drug to targeted drug because now the biology come along identifying specific proteins, specific mutations, specifically targeting in --- in --- brain tu --- glio --- glioblastoma. And then there is some drug available for those. For example the first target that we usually make very popular is EGF receptor.

Tacey Ann Rosolowski, PhD:

Uh-huh.

Wai-Kwan Alfred Yung, MD:

You know, so we test EGF receptor inhibitors in --- in brain cancer. And --- And so we follow that development. There’s also a --- a --- a big effort in --- among the clinical trial group in developing immunotherapy. In fact, I think immunotherapy for brain tumor is one of the early applications. One of the disease cited very early on developing immunotherapy with vaccine --- with tumor vaccine. But the early --- the early development of tumor vaccine in brain in tumor is very crude. You know, mince up the tumor make a --- make a vaccine --- or mince up the tumor stimulate some T-cell, you know. And we go through active immunotherapy to adoptive immunotherapy but

Tacey Ann Rosolowski, PhD:

Very resistant

Wai-Kwan Alfred Yung, MD:

Yeah, very --- very --- you know, most of the result is kind of disappointing. You know. So we --- its --- I mean I think with the --- with the development of the consortium with the, you know, funding of the NCI, you know, research in Neuro-Oncology has growth --- I think vastly expanding, you know. But yet we are still, you know, in search of the magic bullet right now. But on the other hand, the --- the --- the --- the --- the opportunity is much better. Availability of drug is much better. Availability of funding is much better. We also was aided --- I think ---- We’re also, you know, fortunate that we were also aided by some private funding. There are more, you know, foundations established by patient family and philanthropy group. So that also was developed in the --- you know, in the ‘90s and 2000s. Tacey Ann Rosolowski So it sounds like

Wai-Kwan Alfred Yung, MD:

And --- And I think we are front and center in that, really, phase of development at Anderson.

Chapter 11: Creating Networks for Clinical Trials

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