Is a Clinical Trial Right for You?

Before the U.S. Food and Drug Administration (FDA) approves a medication or treatment for public use, it first must go through several phases of study which is known as a clinical trial. During each phase, researchers evaluate how well the treatment works and take note of any side effects.

Clinical trials are key to bringing new treatments to patients, as we have seen with melanoma. Through the efforts and commitment of many patients, as well as companies, doctors and researchers, there are 11 new melanoma treatments approved by the FDA since MRA’s founding in 2007.

The pharmaceutical or biotechnology companies developing the drug provide funding for the studies. However, their research teams rely on medical organizations, such as cancer centers and patient groups, to find people who are willing to participate in the clinical trials.

Deciding whether or not to join a clinical trial is a complex decision. If you or someone you love is considering a clinical trial, you might consider the following.

Things to Consider About Participating in a Clinical Trial

  • Early access to new, and possibly improved, treatment: One of the goals of a clinical trial is to see if a new treatment, or a combination of existing treatments, works against the disease and what side effects it may have relative to the standard of care that’s currently given. It’s possible that the treatment you receive in a clinical trial will be an improvement over existing treatments. However, there’s no guarantee; just because results look promising in a lab does not mean that a treatment will work well in humans. And sometimes something looks promising in early trials but does not end up being effective once tested in late phase trials. It’s possible that the new treatment will help others, but it won’t help you. (By the way, participants in cancer treatment studies never receive a placebo, or “fake,” treatment. Instead, the new treatment is usually studied in comparison to the current standard therapy.)
  • Side effects: One of the goals of a clinical trial is to figure out a treatment’s side effects and their severity. Medications affect everyone differently. However, it is possible that you may experience mild to severe side effects.
  • Frequent, expert medical attention: Doctors and care teams must closely monitor health-related changes in clinical trial participants and record the effects of a treatment, its side effects, and to gauge how well it’s working. That could mean extra trips to the doctor’s for checkups, blood tests, and biopsies. But that means you will have more one-on-one care.
  • Free or low-cost treatment: The research company may offer the new treatment at no or low cost to you. But even if a research company covers medication costs, you could still be responsible for copays for extra office visits and tests. Check with your insurance provider before you agree to a clinical trial and find out what expenses you have to cover.
  • Help save lives: The melanoma treatments available today exist because other people agreed to try them out. What researchers learn from your participation in a clinical trial could benefit the health of other patients. In general, cancer patients seem highly willing to be part of the movement to improve the nature of treatment for others with this terrible disease. But new treatments could be made available even faster if even more patients participated in the clinical trial process.

Since its founding in 2007, the Melanoma Research Alliance has committed nearly $68 million to fund melanoma research, and has supported 21 clinical trials. With our help – and the help of patients – researchers will continue to explore new ways to fight melanoma and other cancers.

Read more about research funded by the Melanoma Research Alliance and what it takes to develop a new cancer treatment.

 

 

Research Q & A: Dr. Michael Atkins

In the latest blog series, we talked with Dr. Michael Atkins, Deputy Director of the Georgetown-Lombardi Cancer Center at Georgetown University, and a member of the MRA Medical Advisory Panel.

Michael Atkins

How did you get interested in melanoma and your field of research?

I had a couple of high school friends who developed melanoma, including someone who died during high school, so I was aware of the disease. In college, I developed an interest in cell biology and immunology. We knew at that time that soluble/diffusable factors could stimulate the immune system at a distance, but no one understood how it worked. I knew that I was interested in oncology because of my interest in cell biology and immunology and I wanted to be involved with patient care. As an oncologist, you’re always an important part of any patient with cancer’s medical team.

My fellowship in hematology/oncology was right around the time that Interleukin-2 (IL-2) was being investigated at the National Cancer Institute, and I got involved in a laboratory researching immunotherapy. The immunotherapy tended to work best in patients with melanoma. So, I was in the right place at the right time and things just came together.  My research interest in immunotherapy and my clinical and personal interest in melanoma intersected and led me to focus on this area.

Explain how your research is making a difference for people with melanoma.

One of the most surprising and gratifying aspects of my work has been seeing how many patients with melanoma can actually respond to immunotherapy. The identification of the immune checkpoints that dampen the immune response and subsequent successful efforts to block them and restore anti-tumor immunity with checkpoint inhibitors has revolutionized the way we treat advanced melanoma and some other cancers. I am continually impressed at how many patients have immune cells that can recognize and destroy their tumors once re-activated.

Further, our advances in melanoma immunotherapy have paved the way for similar advances in patients with all kinds of cancers, many of which we never dreamed of being responsive to the immune system.

Have there been any recent advances in treatment/your research that are particularly encouraging?

In my mind there are three important areas that the melanoma community is actively researching:

  1. Integrating immune therapy with molecularly targeted therapy. We’re looking at the impact of one treatment on the potential responsiveness of other treatments. What’s the appropriate sequence in patients with tumors bearing a BRAF mutation? Does the sequence make a difference? It’s an important practical question that physicians face every day.
  2. Recent work on checkpoint inhibitors suggests combination checkpoint inhibitors have an advantage over single agents. Studies are showing that patients are experiencing better outcomes if we target the multiple immune checkpoints simultaneously, so combination therapy has to be explored and we have to look at which combinations are most active in particular patients.
  3. Using biomarkers to make treatment recommendations. We’re trying to answer important questions, like who can respond best to combination or single agent therapy, and can you “rescue” patients given single agent after they have been given it if it doesn’t respond?

How has MRA funding helped your work?

We’re trying to better understand how other therapies, like molecularly targeted therapies, affect immune responses in the tumor microenvironment. MRA supports my research related to a clinical trial where we perform serial biopsies on patients’ tumors who are receiving BRAF inhibitor therapy. Our goal is to determine if there is an optimal time to start immune therapy after BRAF inhibitor therapy, and if giving it even makes sense.

Five years ago, median survival for patients with advanced melanoma was still 6-9 months and had remained constant for decades. When MRA stepped on the scene, there were new potential targets – like BRAF, CTLA4 and PD1– that had recently been identified. Funding from the MRA has been critical to expediting our understanding of how to optimally exploit these various targets. As a consequence, there is essentially no median survival for patients with advanced melanoma. We may have been able to get to this position eventually without the MRA, but the MRA support has enabled us to do so at practically light speed.

A Father Shares His Family’s Journey with Melanoma

By Skip Grinberg

In this guest blog post, Skip Grinberg shares his family’s experience with melanoma and his drive to advance research.

Skip Grinberg and his extended family

Skip Grinberg and his extended family

Life can occasionally throw you a sharp-breaking curveball. As a result, you may find yourself involved in issues and campaigns that you never could have anticipated. My interest in melanoma and participation with the Melanoma Research Alliance (MRA) fall into this category.

Two years ago my son, Lee, called to tell me that he had been diagnosed with melanoma that had metastasized to his brain. It was one of those phone calls you never want to receive – one that completely refocuses your life.

Lee had surgery a few days later to remove two brain tumors. After surgery he began investigating treatment options, including immunotherapy drugs, most of which were only available in clinical trials. He was fortunate to contact another melanoma patient, Jeff Rowbottom, who has been very active with MRA. With the help of Jeff and MRA, a new universe of information opened, assisting Lee in his understanding of the disease and treatment options. In December 2013, Lee entered a clinical trial – he received a combination of nivolumab and lirilumab, experimental immunotherapy drugs developed by Bristol-Myers Squibb.

As I followed Lee’s treatment, I became aware of the sharp rise in the number of melanoma cases and, in particular, the disturbing increase in diagnosis of young adults. I also became aware of the progress made in the past few years in the treatment of melanoma and the leadership role that MRA has played in funding research grants that have made these advancements possible.

In February 2014, I joined Lee at the MRA Annual Scientific Meeting in Washington. I was thoroughly impressed by the dedication of the researchers, the extent of the research being explored and its implications for the future – not only for the treatment of melanoma but also for other forms of cancer.  Although the research presentations were way over my non-scientific head, I was able to digest enough “big-picture” information so that I could explain immunotherapy to my friends and family.  The meeting also provided an opportunity to network with other melanoma patients and their families and many of the professionals working in this field. The experience further emphasized how MRA has been instrumental in the advancement of knowledge that has benefited Lee and many other patients, giving them something that had rarely existed in the world of metastatic melanoma – hope for the future.

I was very grateful and knew I had to do my part. I created a personal letter telling Lee’s story and sent it to friends and relatives, probably about 150 letters in total. The goal was twofold: to raise funds for MRA and to educate people on the seriousness of melanoma and the progress being made in its treatment. The response was overwhelming and personally very gratifying. Not only did MRA receive a significant number of contributions, but many people called to thank me for informing them about melanoma and to express support for Lee and wish him well. I am now starting to work on the second phase of my personal campaign for MRA. I am excited about it and hoping it is as successful as the first. In addition, our entire family supported #SunHatSat last Memorial Day weekend, to raise awareness about melanoma prevention. We took a photo of four generations of our family wearing hats that weekend at a family picnic.

As I said at the beginning, I never would have expected to be involved with MRA, but I am so glad I am because of the positive impact the organization is having on Lee and thousands of other patients. Our entire family is forever grateful.

Ups and Downs for Melanoma. But Staying Focused.

By Louise M. Perkins, PhD

Chief Science Officer Louise Perkins Headshot

This time a week ago I was jubilant. The SU2C-MRA Melanoma Dream Team’s paper describing a precision medicine approach to treating patients had just been published. And in the middle of the week an important article published in the prestigious scientific journal Cell describing the comprehensive genomic landscape of over 300 melanomas by The Cancer Genome Atlas team – an enormous work that allows us to better understand and target melanoma.

Clearly, with all of this information at our fingertips, with new immunotherapy treatments, with targeted therapy options and new ways to precisely match treatments to patients we have never been closer to defeating this disease. So much progress! I was so excited.

This week I got a text that brought me back to the real world.

In April, I met a businessman at the Milken Institute Global Conference. He told me of his friend, J, who had advanced melanoma. He asked if I might try to help J in some way. I spoke with her and learned that fortunately, she was already connected with some of the leading docs in melanoma. She’d gotten all the new treatments. But she wasn’t doing great and felt like she needed to move back home to be closer to her mom. I had a chance to learn her story and get to know her a tiny bit and was hopeful that things might turn out well.

The text I awoke to let me know that J. died earlier this week. At 32, she’d lost her fight to melanoma.

Earlier this week, MRA met with folks from the FDA along with two leading melanoma experts (Michael Atkins and Paul Chapman) to discuss the latest in the field from the recent cancer meetings. These conversations help to identify new opportunities and help keep the focus on melanoma. The FDA colleagues are great, by the way, and have been amazing partners in bringing new treatments to patients with melanoma very quickly.

In the discussion, both Drs. Atkins and Chapman pointed out that older melanoma patients, the ones who would typically be least likely to tolerate and respond to chemotherapy, actually seem to respond to AND tolerate checkpoint therapy (anti-CTLA-4 and/or anti-PD-1) treatment better than younger folks. The reasons for this aren’t quite clear but two possible explanations spring to mind. Perhaps the tumors in these older individuals have more mutations acquired over a long life and so have more ‘hooks’ for the immune system to latch on to and recognize as foreign. Another hypothesis is that the older folks have immune systems that aren’t as robust as those in younger patients. That robust immune system might get a little overactive in young folks – harming good cells alongside the tumor ones (leading to more side effects) and also prematurely turning off the anti-tumor response.

Is it possible this is like the Spanish Flu where younger, fitter patients were more at risk than older patients? Researchers are working on understanding the differences between responders and non-responders to try to determine what might be tweaked to elicit more and more responses in patients. One of the key takeaways from the meeting with the FDA was the need to continue to focus on those patients who aren’t fully benefiting from current therapy to understand the unique features of their melanoma and work together to beat it. We talked about sub-types that form in the eye, the mucosal surfaces and on non-sun-exposed sites like soles of the feet. We talked about melanoma that has metastasized to the brain – a vexing problem for too many. All of these patients who don’t respond to treatments, old or young, need better options.

Unfortunately, it is too late to help J, or Jackie, or Tara – the young women MRA got to know in the last two years – or Claire, the 17 year old who went to my high school. The deaths of these young women put a fine point on the urgency to keep the pressure on for all melanoma patients to find a cure.

Thanks to all of you for funding the research to understand what’s different and what to do to change the outcomes for patients like these young women – and all of those with advanced melanoma. We’re committed and appreciate your commitment, too.

About the Author

Louise M. Perkins, Ph.D., joined the Melanoma Research Alliance (MRA) as Chief Science Officer in 2013 where she is responsible for the development and implementation of MRA’s scientific strategy.

On the Path to Precision Medicine for Melanoma Patients

By Louise M Perkins, PhD
Chief Science Officer

There is no denying the transformative success of new treatments for melanoma ranging from molecularly targeted agents for BRAF-mutant melanoma to immunotherapies like anti-CTLA4 and anti-PD-1 drugs. Indeed, the treatment of BRAF-mutant melanoma is a prime example of Precision Medicine; that is, matching treatments to a patient’s specific disease.

Yet, despite the progress, about half of melanoma patients lack a BRAF mutation and treatment resistance to immunotherapy is far too common. New strategies for these patients cannot come quickly enough.

Expanding Precision Medicine in Practice

Since 2012, the SU2C-MRA Melanoma Dream Team has been working on one such strategy, a Precision Medicine approach – similar to what President Obama advocated just a few months ago – with joint funding by both the Melanoma Research Alliance (MRA) and Stand Up to Cancer (SU2C).

The first publication describing the pilot phase of the Melanoma Dream Team’s genomically guided therapy study appeared online recently in the journal Molecular Cancer Therapeutics. The team piloted its approach to ensure that state-of-the-art genomic information could be produced with biopsies from patients with melanoma that could be useful for treatment decision-making in a timely way. While this idea may sound simple, it is no easy feat, with many real-world logistical and technical challenges.

Teamwork is a key feature in overcoming many of these challenges, including starting and running a complex trial of this sort involving multiple centers and high-tech analyses. But state-of-the-art science is also needed. The team’s cutting-edge sequencing machines and expertise in genomics is critical to produce and analyze the genomic data. This genomic data can help spot tumor-specific mutations that might be susceptible to therapeutic treatment. Together, the teamwork, expertise and technology provide the means to unlock a better understanding of how to offer treatments tailored to the unique genomic features of one’s own tumor.

Sharing Lessons Learned

The important lessons learned in this pilot have already been shared widely in meetings with researchers to speed the startup of similar studies across cancers. And participants from programs like NCI-MATCH and LungMAP have been actively sharing information on this topic, too. It is gratifying to see the Melanoma Dream Team’s programmatic advances disseminated world-wide through this recent publication.

What’s Next?

It is important to ask how well such a Precision Medicine approach works with larger numbers of melanoma patients, as the field continues its efforts to overcome resistance to available treatments and work toward wider adoption of Precision Medicine.

To that end, the Melanoma Dream Team has several sites around the country that are enrolling eligible patients with melanoma who have progressed on (or are ineligible for) approved immunotherapies and who lack a BRAF V600 mutation that would qualify them for molecularly targeted treatments.

The Latest in Melanoma Research: News from the Two Biggest Cancer Meetings

By Louise Perkins, PhD
Chief Science Officer

There’s been a lot of news on melanoma treatments in the last couple of weeks coming out of the two largest cancer conferences held each year: the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) annual meetings. The results – particularly in the area of immunotherapy – really are exciting for the field of melanoma and cancer, at large.  On the Diane Rehm Show this week, melanoma was described as the “poster child for immunotherapy,” which it certainly has been.

So what’s new, and what does it mean now and for the near future?

Melanoma drugs circa 2014

In September and December 2014, two new melanoma treatments were approved by the FDA for advanced metastatic melanoma. These are the anti-PD-1 drugs pembrolizumab (pembro, Keytruda®) and nivolumab (nivo, Opdivo®). Pembro and nivo release the so-called “brakes” on the immune system, to help the body’s own immune system fight cancer. Another drug, ipilimumab (ipi, Yervoy®), is an anti-CTLA-4 drug and was FDA-approved in 2011.  Check out our video that describes how these immunotherapies work.

The latest news from early 2015
Researchers have been trying to answer a few important questions about these new immunotherapies, such as:

  1. Is anti-PD-1 (pembro, nivo) treatment better than anti-CTLA-4 (ipi) in patients who have not had any prior therapy?
  2. Do anti-CTLA-4 and anti-PD-1 in combination work even better than either treatment alone for patients who have not had any prior therapy?

MRA-funded investigator Jedd Wolchok, MD, PhD, and colleagues addressed the latter question in a Phase 3 trial at ASCO. The study involved more than 900 previously untreated metastatic melanoma patients and compared three different therapies:

  1. Ipi alone
  2. Nivo alone
  3. Ipi and nivo in combination

They found that nivo either alone or in combination with ipi had better results for patients than ipi alone.

This is similar to what was reported at AACR by Antoni Ribas, MD, in a Phase 3 study of the other anti-PD-1 drug pembro, which showed that pembro was better than ipi in previously untreated patients.  More trials are underway to confirm whether or not the combination allows patients to live longer (overall survival) versus single-agent therapy.

One important piece to note is that recent studies found that the increased benefit of the combination also comes with increased side effects; in fact, approximately one-third of patients discontinued therapy due to side effects.

At ASCO, Michael Atkins, MD, summarized these clinical findings that have been presented over recent months:

  • Nivolumab is better than ipilimumab alone
  • Pembrolizumab is better than ipilimumab alone
  • Nivolumab and ipilimumab in combination are better than ipilimumab alone

What does this mean for melanoma patients?

Believe it or not, things are moving amazingly fast. So what does all of this mean for patients in June 2015, just 9 months after the first anti-PD1 treatment was approved by FDA?  Well, one leading cancer guideline group, the National Comprehensive Cancer Network, already updated its melanoma treatment guidelines in March to recommend that oncologists consider a single-agent anti-PD1 (either nivo or pembro) as first line treatment for advanced metastatic melanoma patients (pembro and nivo were FDA approved for patients who have progressed on prior therapies).

More research is needed to determine if and when and for which patients the combination of anti-PD-1 and anti-CTLA-4 should be used.

Breakthrough Medicine: Highlights from Milken Institute’s Global Conference

Earlier this week, Melanoma Research Alliance Chief Science Officer Louise Perkins, PhD, moderated a panel at the 2015 Milken Institute Global Conference. Titled “Breakthrough Medicine: Will Finding a Cure Be Just the Start of Saving Lives?” the panel featured experts across the medical landscape, from industry to practitioners to insurers. With new therapies showing real promise and a national focus on precision medicine, this is an exciting time for science, yet challenges remain.

“The cost to create breakthrough drugs threatens to break the innovators who develop them, as well as the institutes who pick up the tab to pull them forward,” said Dr. Perkins.

Read more about the panel on the Milken Institute’s Currency of Ideas blog or watch the video.