11 November 2013

One of the first things that might be discussed when you are looking at your cancer treatment options is whether or not there are clinical trials that you might qualify for. While many still view clinical trial participation as being a “guinea pig” in an experiment, it is important to understand that the clinical trial process is designed to protect patients. Any clinical trial needs to be overseen by an Institutional Review Board (IRB), an independent ethics and monitoring body dedicated to protecting human subjects from physical or psychological harm.

If it were not for clinical trials, we would still be performing radical mastectomies on all women with breast cancer – randomized studies have shown us that more aggressive surgery does not lead to improved outcomes. We are able to offer shorter courses of radiation therapy thanks to the data generated from large studies, and medications such as trastuzamab, previously used only in patients with advanced metastatic disease, are now considered first-line therapy in selected patients with early-stage cancer.

The post discussing clinical trials was written by Carmen Gonzalez, Communications Project Manager at Heath Services Advisory Group of California, Inc., and originally appeared on the #BCSM Community Website.

Clinical Trials 101 – Guest Post by Carmen Gonzalez
The world of clinical research can present a hornet’s nest of almost incomprehensible clinical jargon to the average Jane or Joe. Added to that reading burden is finding what study is right for you.  Assuming you have waded through all the public information, there remains the task of asking the right questions so that your experience is productive, worthwhile, and fits your life. In this blog, I will cover “just the basics,” arming you with the essentials to find what you need.

How to Find Them
If you are starting at square one, you probably don’t know how to find clinical studies. First, start by inquiring from trusted sources, including your doctor and other medical professionals with whom you’ve established trust.  If searching for breast cancer-related studies, visit disease-specific sites where patient-centered resources are available which feature clinical studies, e.g. The Susan Love Research Foundation’s Army of Women. Being the empowered patient that you are, expand your knowledge of available studies further by seeking out online clearinghouses, such as BreastCancerTrials.org, a non-profit dedicated to helping breast cancer patients connect with researchers. BreastCancerTrials.org compiles the trials from ClinicalTrials.gov. and Cancer.gov—comprehensive libraries of ongoing studies— into one hub, so it saves you two less searching chores. There’s an added benefit with BreastCancerTrials.org: they use your health history to guide you to the right trial, and they eliminate a lot of clinical jargon that can trip up novices to clinical research. While you can choose to see all the trials available, their screening tools make it easier to find what you need.

If you do decide to explore ClinicalTrials.gov directly to explore clinical studies, be forewarned: technical clinical language lies ahead. Search  trials by inserting general terms, such as “breast cancer,” “stage 2,” and “HER-positive.” To tame what could be a fire hose of responses, insert search terms that narrow your focus, such as the disease topic with your location and other distinctive traits, e.g. “Chicago” AND “breast cancer” AND “metastatic cancer.”

Here are a few rules of the road when considering different categories of studies.  Research trials are either observational or investigational, meaning only as to the latter are patients given a treatment. There are four basic types of investigational studies : Phase I, II, III, and IV studies.

Phase I refers to studies which are being conducted for the first time in humans, having been successfully tested in animal models. Phase I studies are exploring the safety of the drug or device, and are typically involved with  small number of participants.
Phase II studies involve a larger group of study volunteers to test if the drug or device is effective, commonly against a placebo. If a drug or device is successful in its phase I and II stages, then a significantly larger study group is involved in a Phase III study.
Phase III studies help to determine if the drug or device is as good or better than the standard of care. During this phase, issues of safety are also closely watched. While success at the phase III stage poises the drug or device for likely market approval by the FDA, another phase is needed.
Phase IV is imposed to see if late-breaking safety issues arise in the wider marketplace. What does this boil down to for you? The more phases the drug or device has passed successfully, the safer it  has proven to be. Foolproof? No. Remember Vioxx? That’s why Phase IV is so important.

What to Ask About
Whether you are healthy or sick, an appropriate clinical study has to fit into your life for it to be meaningful and worthwhile. That means that you need to have a full understanding of the study’s implications to your health and full knowledge of the obligations before you. Let’s consider these topics separately. First, dig into whether this study offers you significant personal benefit, and if it advances the science in the field. Start by asking how this study advances scientific knowledge and how it improves your prospects of recovering, improving, living longer, or in better managing your disease.
Ask the study team if the research offers a novel treatment, device, or delivery method.  Once you get answers to these questions, mull them over with your doctor if you’re unsure of its potential benefit to you.

Once the overarching considerations meet with your satisfaction, use the following checklist when asking the clinical study team about the study’s logistics:

  • Are there any anticipated side effects? What are they and their severity?
  • How long is my study obligation? (e.g. number of days, weeks, months, years)
  • How many visits in total will require my in-person presence at research clinic?
    • How many visits per week or month does this mean for me?
  • Are there additional visits to other specialists beside the research clinic? (e.g. imaging tests at a radiology lab)
    • How far away are these office from the research clinic?
  • What other study duties are required of me?
    • Is there a diary I have to keep?
    • Am I required to take study medications at home?
    • Is there a medical device I have to use?
    • Are there dietary or activity restrictions?
  • Are there any post-study activities required of me? (e.g. phone check-ins)
  • What is the stipend offered for my participation? Is my travel compensated?
  • When will the study officially end? When and where can I obtain the study’s results?

Once you inquire about what is involved, now ask about the likely impacts on your family. This is often overlooked and leads to unanticipated conflicts, so tackle them beforehand. While you can walk away from any study at any time, it will save you considerable time and frustration to find the right fit upfront. Consider asking the following:

  • Does the schedule conflict with family vacations or other commitments? Is there a way to accommodate these priorities? For example, if study visits are required at a time of day that is inconvenient, will the team consider other time slots or weekends?
  • Does the study impose obligations that conflict with your religion? Take the fasting periods of Ramadan for example, and some studies conducted during the summer might not work with your requirements.

Be realistic about where you are in your emotional life as well. If you are undergoing grieving for a marriage or loss of a loved one, you might not be ready to be a study volunteer. Acknowledge your own expectations and biases regarding the study and discuss those reservations and hopes with the study team. They can provide able counsel to help you determine if participation makes sense at this moment.

What To Expect
If you are placed in a control group—study volunteers who are not receiving the active study medication or device—then any positive response you experience will be attributed to what is called the “placebo effect.” You won’t know whether you were assigned to a placebo or “active” group, as that would defeat the scientific process. However, sustained dramatic improvement tends to suggest that patients were in the “active” group. For patients to gain answers to which groups they were in and the overall impact of the study, they must wait for the trial’s conclusion. In the U.S., study teams are required to post their results on ClinicalTrials.gov upon completion, but faithful adherence is spotty at best. To ensure you get the answers you need, aside from your personal outcome, request the results from the study team and create a tickler on your calendar to remind those in charge to keep you posted.

If during the course of the study, you experience unwanted side effects, immediately report your symptoms to the study team right away for intervention. Depending on the study, there are some minor  side effects that are anticipated, but in all cases, report your experience no matter what. For patients with multiple pre-existing medical conditions, there may be fewer studies for which they are eligible, but that rarely rules out everything.

In studies that span several months or years, the mere slogging pace of the study can impose a weariness commonly called “study fatigue”—not an ailment, but an acknowledgement of growing impatience. Be honest with yourself if you can endure a long-term study and the duties that come with it. While you can’t predict all the events that might upset your study schedule commitments, understanding and knowing how you manage everyday routines will give you a candid idea of your likely study visit consistency. Armed with these tips, you can make better decisions concerning study involvement.

PBS Need to Know: Dispelling the Myths Surrounding Cancer Trials

3 August 2013

What’s in a name? In the case of cancer, there are myths, fears, and misinformation – more than perhaps any other illness.

Cancer encompasses hundreds of different diseases and each one is complex. Even women diagnosed with exactly the same “type” of breast cancer and who undergo the same treatment can have very different outcomes. Not all cancers are equal and not all cancers are lethal.

While early detection and treatment were once equated with improved survival, we now know that tumor biology (characteristics governing the behavior of spread and response to treatment) plays an extremely important role in the prognosis of an individual cancer. There is an increasing recognition that current screening tests, meant to diagnose cancer in the earliest stages, will often diagnose lesions that have minimal potential to become aggressive or lethal. As our screening technology improves, we are detecting more patients in early stages or with pre-cancerous conditions and we are treating those patients with surgery and other potentially toxic therapies.

In 2012, the National Cancer Institute convened a working group to “evaluate the problem of ‘overdiagnosis’ which occurs when tumors are detected that, if left unattended, would not become clinically apparent or cause death.” Unrecognized overdiagnosis, they stated, “generally leads to overtreatment”1.

The recommendations of this panel were recently published in the Journal of the American Medical Association: Overdiagnosis and Overtreatment in Cancer, An Opportunity for Improvement.  The authors provide five recommendations:
1. Physicians and patients alike need to acknowledge that screening results in overdiagnosis – especially in breast, lung, prostate and thyroid tumors.
2.  The term ‘cancer’ should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated.
3.  Create observational registries for low malignant potential lesions in order to better understand prognosis and best treatment options.
4. Mitigate overdiagnosis with an ultimate goal of preferential detection of consequential cancer while avoiding detection of inconsequential disease.
5. Expand the concept of how to approach cancer progression by controlling the environment in which cancerous conditions arise.

While these are certainly laudable goals, some important points should be made, especially in regards to breast cancer and ductal carcinoma in-situ – the most important being that we do not currently have biomarkers or other indicators that can clearly distinguish a potentially lethal cancer from a more indolent one. The field of cancer genomics is rapidly changing, and today more than ever, we can obtain very sophisticated prognostic information regarding an individual’s tumor. Despite that, Dr. Larry Norton, medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center, stated “Which cases of DCIS will turn into an aggressive cancer and which one’s won’t? I wish I knew that. We don’t have very accurate ways of looking at tissue and looking at tumors under the microscope and knowing with great certainty that it is a slow-growing cancer”2.

Regarding the modern management of DCIS, there are three points to remember:
1. When DCIS lesions diagnosed by needle core biopsy are surgically removed (which involves removal of substantially more tissue from the abnormal area), there is an approximately 15% rate of ‘upstaging’ to invasive ductal cancer 3. Put another way, one cannot always reliably predict the behavior of an entire lesion based on a core biopsy specimen.
2. During surgery for DCIS, axillary lymph node metastases have been demonstrated up to 20% of the time, usually indicating missed microinvasion or invasion 4.
3. Finally, if DCIS recurs, 50% of the time it is invasive 5.

What is important to be aware of is that any woman with breast disease, including DCIS, should be presented with the information necessary so that she may gain an understanding of where her diagnosis stands in the biological spectrum and the wide array of choices she has for treatment. DCIS is far from simple, and it is not to be taken lightly. Clearly there are cases where ‘watchful waiting’ is safe – but we cannot always reliably predict who will truly benefit from treatment. Moving forward, we need to be aware of the facts – what medical technology can provide the patient and the physician now, and we need to ask how we can drive this conversation in the future.

Deanna J. Attai, MD, FACS
Michael S. Cowher, MD