Moon Shot deploys policy help, education and clinical trial innovation
against tobacco use
Clayton Boldt, Ph.D.
November is Lung Cancer Awareness Month, and the third Thursday of each November is designated by the American Cancer Society as the Great American Smokeout – a day focused on encouraging Americans to quit smoking.
Tobacco cessation and prevention have long been an area of focus and expertise for MD Anderson, and has been a critical component of the Lung Cancer Moon Shot® since its inception. The effort is part of MD Anderson’s Moon Shots Program®, a collaborative effort designed to accelerate the development of scientific discoveries into clinical advances that save patient’s lives.
To explain more about these prevention efforts and an innovative new cessation trial, Cancer Frontline spoke with Paul Cinciripini, Ph.D., chair of Behavioral Science and leader of the Moon Shot’s prevention flagship.
Q: Why is cancer prevention such an important area of work for the Lung Cancer Moon Shot?
A: I think cancer prevention is important, not only for the Moon Shot, but for all of MD Anderson, for the same reasons. It costs less and we can accomplish more in terms of reducing the burden of cancer and other diseases by doing something preventive.
In our case, we’re after smoking: the single most important risk factor for 12 different types of cancer, including lung cancer. Quitting smoking at the time of cancer diagnosis can reduce risk of dying 20-40%. Smoking remains the leading cause of premature death and disease in our country, and by helping people to quit or preventing them from starting tobacco use, we can a have dramatic impact on public health.
Q:What have been some of the key projects and successes of the prevention flagship thus far?
A: We’ve focused on several aspects of prevention since our efforts began. We’ve had a continuing investment in adult smoking cessation, and the Lung Cancer Moon Shot has supported several clinical trials in this area. This has also enabled us to secure additional grant funding to expand our efforts and broaden our research.
We also have a focus on youth prevention, and early on that started with the re-facing of ASPIRE (A Smoking Prevention Interactive Experience), a program created by Dr. Alex Prokhorov. We completed the update of ASPIRE, and the new version is being implemented in multiple schools across the country.
Additionally, we have worked with our EndTobacco® team to serve as clinical and scientific resources for legislators considering important public health policies. Just this year, Texas legislators voted to increase the minimum legal sale age for tobacco and nicotine products from 18 to 21. This is an important step to protecting the health of our young people.
Another area the Moon Shot has focused on is professional education and development, which led to two major projects. Working again with EndTobacco, the Moon Shot supported the development of the Certified Tobacco Treatment Training Program to offer training and certification to providers interested in offering tobacco cessation. We utilize the Project ECHO telementoring model to provide sustained learning opportunities for those providers as well.
Finally, EndTobacco spurred the creation of the Eliminate Tobacco Use initiative through The University of Texas System. This effort started in 2015, and we have worked with all UT System institutions to help them become tobacco-free as well as develop their cessation and prevention capacity. We’ve since expanded to include other universities and groups across Texas and the country, and we’ve been really pleased to see all this come together so well.
Q: What projects are you currently most excited about?
A: Our focus now in on Project PISCES, which is the most innovative and largest trial we’ve ever done. PISCES will provide the scientific basis from which we will design a tool to “personalize” smoking cessation pharmacotherapy, by assigning patients to the treatment that optimizes their chance at success.
Its’ a two-part trial, and in PISCES-I we use a “SMART” design. Most clinical trials are done by assigning participants to different treatments and comparing the treatments at the end of a set time period to see which did better. In a SMART design, a patient is assessed for success after an initial treatment, then given a subsequent treatment early on if the treatment fails.
In PISCES, participants will be randomized to one of the best two currently available treatments, either dual nicotine replacement or varenicline. After five weeks, we’ll assess their progress.
If they’ve successfully quit, they’ll remain on their current treatment. If they haven’t quit, we’ll randomize them again, either to remain on the same treatment for a longer period, switch to an alternate therapy, or augment the current one by adding another medication and/or increasing the dose. Nothing like this has been done before. We call this second phase of the trial the rescue treatment, because we’re working to help those who haven’t been able to quit or have relapsed.
For this to be successful, we’ll be recruiting 2,000 current smokers from across Texas. The only way we can accomplish this is by doing all treatments remotely, using a smartphone and digital platform developed specifically for PISCES. This complete remote pharmacological and behavioral intervention is another first.
The reason it’s so large is because our purpose is to learn about the individual differences among our participants that will predict their response to a given treatment. We’re looking at baseline characteristics such as nicotine dependence, psychiatric co-morbidities, mood, cravings, age, gender and race, as well as a panel of genetic markers we have previously found predictive of overall abstinence and severity of nicotine withdrawal.
The idea then will be to say, based on these characteristics, “What is the best treatment choice for a given individual?” In PISCES-II, we’ll take information we’ve learned from PISCES-I to build an algorithm that will take all these characteristics into account and prospectively assign people to the best treatment for them.
We’ll compare the success rates of those assigned to treatment using the algorithm relative to success rates of those given usual care – standard nicotine replacement and counseling. If we can show this algorithm performs better than usual care, this could change clinical practice by giving providers a means to personalize treatments and optimize a patient’s success. We plan to develop an app that providers can use to choose the initial treatment assignment, as well as the best possible rescue therapy if that should fail.
Q: How is your work enabled by the Moon Shots Program and its infrastructure?
A: A trial like PISCES would be too large for any one treatment center to do. By making it all digital, we’ve been able to produce an innovation we would never have been able to without Moon Shot support. These are high-risk, high-gain studies that are rarely funded by NIH. We could only do a trial like this with Moon Shot support. That’s paid off thus far, because we’ve been able to leverage this support for our other trials to obtain NIH and CPRIT funding.
We know we can be successful, because we’ve already been able to use Moon Shot support to develop a prototype of the algorithm, using data obtained from several of our past trials.
In my mind, that’s what the Moon Shots Program was designed for in the first place – to really take risks. To think of what you could do that would have the biggest impact. So we’re very grateful for the Moon Shot support because there’s no way we could have made this many strides, or done this kind of innovative trial, without it.
Paul Cinciripini, Ph.D., says Project PISCES “is the most innovative and
largest trial we’ve ever done. PISCES will provide the scientific basis
from which we will design a tool to “personalize” smoking cessation
pharmacotherapy, by assigning patients to the treatment that optimizes
their chance at success.”