Archive for July, 2016

Talking About Metastatic Breast Cancer Trials 

Welcome to our summer newsletter“Talking about Trials” or, more specifically, talking about metastatic breast cancer trials.
No one knows precisely how many people are living with metastatic breast cancer. The Metastatic Breast Cancer Network reports the number is estimated to be more than 155,000. What we do know is that up to 10 percent of women diagnosed with breast cancer have metastatic disease, and that up to 30 percent of all breast cancer cases will become metastatic. We also know that metastatic breast cancer kills about 40,000 women each year.
Clinical trials are important options all breast cancer patients should consider. They are especially critical for those with metastatic disease, because it can give these women access to the new targeted therapies and immunotherapies that are being developed. As this interactive chart developed by Metastatic Breast Cancer Alliance (MBCA) shows, as of July 2015, there were 204 metastatic breast cancer trials underway–and more have been added since then.
To get results, these trials need to enroll close to 27,900 patients. We are proud to be a member of the MBCA research task force, and be contributing to the Alliance’s aim to ensure all women with metastatic breast cancer know their participation in research trials is needed.
As part of this effort, and with support from the Avon-Pfizer Metastatic Grant Program, we worked over the past year with five other breast cancer advocacy groups to launch Metastatic Trial Search, the first and only clinical trial search engine specifically for people with metastatic breast cancer.
In this issue, we speak with two breast cancer researchers who want to see new areas explored in metastatic clinical trials–Dr. Patricia Steeg and Dr. Gabriel Hortobagyi. We hope you enjoy learning about their ideas and insights. We also hope that this issue leaves you inspired to explore trials for yourself as well as share this information with others you know, especially those living with metastatic disease.

Elly Cohen, Ph.D., Program Director, BreastCancerTrials.org

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July 6, 2016 at 11:42 pm Leave a comment

Q & A with Dr. Patricia Steeg, Ph.D.

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Dr. Patricia Steeg

To reduce deaths from metastatic breast cancer, Dr. Steeg believes researchers need to conduct a new type of trial—one that would test drugs that laboratory studies have shown can prevent new metastases from developing. BCT spoke with Dr. Steeg about this new approach to clinical trials.

Q: Why do you think changing the way clinical trials are designed can reduce breast cancer deaths?

A: If we change the way trials are designed, we can enroll patients at different points, treat them with different types of targeted therapies, and use different end points that will still be relevant to patients’ quality and quantity of life.

I am advocating for metastasis prevention studies. The bulk of the preclinical data (studies done in cells and mice) says we can prevent metastases much better than we can shrink ones that have formed. So the question is: Is that true or is that just something we see in mice?

Q: How can you find out?

 A: That’s where the problem is. You can’t do an adjuvant trial that enrolls 1,000 people for each drug that might prevent metastases. (Adjuvant treatment is given after surgery to prevent recurrence.) So, I’m advocating we run smaller trials that enroll either super high-risk patients in the adjuvant setting or patients with limited metastases. The endpoint would be the development of a first or a new metastasis.

Q: Why do you think researchers are resistant to trying this?

A: It is something new. Every time I present this concept to oncology groups they say ‘Pat, of course you are right—but this is not the way we have done trials.

There is limited funding for clinical trials and they are going with what they know. So there is an element of habit, of risk-aversion. Also, I don’t think companies are going to fund these kinds of trials because they have yet to lead to a drug that has been approved by the Food & Drug Administration (FDA). It will take a few brave people with money to run these trials and say, ‘Yes, it works.’ Then more will jump in.

You can learn more about all of the breast cancer trials taking place at the NCI Center for Cancer Research here.

Q: How does what you are talking about differ from regular trials?

A: The trials with the high-risk patients would be mini-adjuvant trials to see if they reduce the risk of recurrence. For the patients with metastases, the trial would look at whether the drug prevents more metastases.

Q: Are there drugs that might stop new metastases from developing?

A: They are called Src inhibitors. They target an enzyme in the cancer cell that plays a role in cell movement and colonization—two things that happen in the metastatic process but don’t happen in a cell sitting still. There were two Src inhibitors that were studied in metastatic trials but those trials didn’t show the drug was effective. But what was measured was whether they shrunk existing tumors. Yet, the literature shows that they prevent new tumors—not shrink ones that are already there. And that’s what needs to be measured—whether they prevented new tumors from developing.

Q: If they could prevent new metastases, how might they be used?

A: The Src inhibitor could be given after standard treatment. I think it would be a maintenance regimen. A patient would have the standard of care and then take the inhibitor for a long time. We are seeing this in lung cancer, where studies are having patients take a low dose of a maintenance drug, and seeing some benefit.

Q: Are you going to do this type of trial?

A: At the NCI we are developing a trial to see if the oral chemotherapy drug temozolomide (which is used to treat some types of brain cancer) can prevent new brain metastases. We found in mice that a low dose of the drug will prevent brain metastases. So we are going to enroll patients with 1-5 brain metastases and treat them with stereotactic radiosurgery (radiation directed at the brain metastases) and then randomly assign half to also start on temozolomide. So, it’s following the standard of care and looking to see if we can prevent new metastases.

The trial Dr. Steeg is developing will take place at the NIH Clinical Center in Bethesda, Maryland. You can learn more about all of the breast cancer trials taking place at the NCI Center for Cancer Research here. Some of these trials cover participants travel expenses to and from the NCI.

You can read more about Dr. Steeg’s ideas about clinical trials in this article published in Nature in May 2012. You can listen to her discuss these ideas here

July 6, 2016 at 11:42 pm Leave a comment

Q & A with Dr. Gabriel Hortobagyi, MD

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Dr. Gabriel Hortobagyi

In 2001, Dr. Gabriel Hortobagyi published an editorial in the Journal of Clinical Oncology that reviewed what was known at that time about treating breast cancer patients with very few metastatic sites. This limited metastases is called oligometastases. BCT spoke with Dr. Hortobagyi about what types of clinical trials are needed to move forward in this research area.

Q: How has research into oligometastases advanced over the past 15 years?

A: This is an uncommon situation, and the problem with uncommon situations is it takes a long time to do research. There’s been very little additional data since I wrote that piece. The reality remains that there is a small percentage of patients with metastases—somewhere around 5 percent—who have oligometastases and, of these, one in three or one in four could potentially be cured with systemic treatment plus surgery or radiation or both.

The data we have show that these patients tend to be younger, in good physical condition and have metastatic disease that can be removed surgically with clean margins in the lungs, liver, brain and maybe some soft tissue. It also seems that patents with hormone-negative tumors are more likely to be cured, which is probably because their tumors are more responsive to chemotherapy.

Q: Does this mean women should have more screening so that more women would be found with fewer metastases?

A: That’s the controversy. It is a huge question, whether we move away from having the guidelines that say no tests should be done regularly and women should just be alert to possible symptoms. Some of us believe that the studies on which those guidelines are based, which were done in the 1980s, need to be repeated with modern technology.

Q: Could this be done?

A: The problem is that it would take 10,000 to 15,000 patients followed for at least five years, and most likely 10 years. And it would cost between $40 and $100 million to demonstrate, or not, that closer monitoring and earlier diagnosis of metastases will identify a subset of patients who could be treated and never develop additional metastases.

Q: Is money the only obstacle?

A: No. There are other concerns. Because so few women develop oligometastases, the majority of the women in the trial would not experience any benefit. So, it is a complicated issue because whenever you deal with uncommon or rare events you face this situation.

Q: Do new technologies create new possibilities?

A: Right now, the tools we have aren’t at a point where we could do this kind of study. But let’s say in two to three years we have the perfect circulating DNA test and we can show that out of 100 patients we find 30 who have circulating DNA and no other abnormality and that all 30 develop metastatic disease—and none of the others do. Then we’d have something much more solid and something we can rely on. But we don’t have that today.

Also, having a test like that means we wouldn’t need such a large clinical trial. We’d only need to identify 200 patients who test positive on the circulating DNA test and then randomize them to treatment or no treatment and that would only cost maybe $3 million as opposed to 40 or 100 million.

Q: Are we getting closer to that type of test?

A: We’re doing research right now to develop this kind of circulating DNA test, with clinical trials at MD Anderson and through SWOG. (SWOG is a worldwide network of researchers that is part of the NCI’s National Clinical Trials Network.)

I know it’s frustrating for patients. It seems like, ‘why are these guys taking all their sweet time doing this when women are dying of breast cancer’ and I am acutely aware of this frustration. But, unfortunately, this is the way things work and it’s the reality of clinical trials. We need to develop solid preliminary data before we can move to more advanced trials. Most of the trials we complete are negative and they don’t move the field forward they just tell us things don’t work. But we still have to do them.

You can learn about trials open at MD Anderson here.

You can learn more about SWOG-sponsored trials here.

July 6, 2016 at 11:41 pm Leave a comment



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