Your Questions about Clinical Trials are Important

The Sarcoma Alliance for Research through Collaboration (SARC) is a non-for-profit consortium of sarcoma experts who collaborate together to do clinical research. A goal of this organization is to design and conduct clinical research that will result in new and better treatment options for patients with sarcoma.

Given SARC members have expertise in sarcoma clinical research, I would like to invite you to pose your questions to these experts and I will have them respond to them via the SARC website.

Whether you are considering becoming involved in a clinical trial, are already enrolled in one, or have completed one, I am very much interested in questions that you might have about clinical trials. Please take time to download and complete the Questions and Concerns about Clinical Trials questionnaire. You can either e-mail it to me or send it to me by surface mail.

	Click here for a Microsoft Word version of the questionnaire.
	Click here for an Adobe PDF version of the questionnaire.

For more on SARC, see Dr. Robert Maki's Op Ed piece, Sarcoma Alliance for Research through Collaboration (SARC): An effort to perform clinical trials efficiently and effectively for people with sarcoma, which appeared in the December 2007 issue of ESUN.

Sarcoma Clinical Trials

Points to Consider

Kelly Scheu, MS, NP-C

Foote Hospital, Oncology Services

Jackson, Michigan

Sarcomas are an uncommon type of cancer. Over the past forty years, sarcomas have been treated with chemotherapy. Standard chemotherapy unfortunately has not been effective for all patients. New treatment options are needed. Sarcoma clinical trials are one way to identify new therapies. Sarcoma clinical trials provide an opportunity to have access to new drugs which have the potential to improve outcomes and hopefully cure sarcoma.

The words “clinical trial” may evoke uneasiness for some people. The thought of having a new drug that is still in the process of being studied may be concerning. Understanding the different phases of clinical trials and as well as having strategies to navigate the clinical trial system may help alleviate concerns.

There are 4 phases to clinical trials.

	Phase 1 clinical trials are the earliest stage of drug development. A phase 1 trial attempts to determine the dosing of a particular drug and the side effects through rigorous monitoring of the patients and frequent testing of blood at timed intervals. Phase 1 clinical trials are generally not specific to any one type of cancer. Often small numbers of volunteers are enrolled in these types of trials.
	Phase 2 trials include more volunteers who have a certain type of cancer that the researchers believe may be helped by the new treatment. In phase 2 trials, researchers seek to gather further safety data (information about side effects) and evidence of potential beneficial effects. If the drug proves to be effective and the side effects acceptable, a drug may then be studied in a Phase 3 clinical trial.
	Phase 3 trials study a drug in a large number of volunteers with a specific cancer. This phase further tests the drug’s effectiveness and in some cases compares a new drug to a standard therapy to see if one is better than the other. Phase 2 and Phase 3 clinical trials can sometimes involve a “control” which means one person will get the new drug and another will get the standard therapy or placebo. The process is usually determined by randomization which is like a “flip of a coin”.
	Phase 4 trials are conducted after a product is already approved and on the market to find out more about the treatment’s long-term benefits and risks.

Many drugs used in treatment today, were initially evaluated in phase 1, 2 or 3 clinical trials prior to approval by the FDA. Clinical trials have rigorous regulations and guidelines to ensure the safety of all volunteers.

There are several important things to remember when considering a clinical trial.

	Identifying what trials are available is the first step. The internet may be helpful. The National Cancer Institute has a website for the Cancer Information Service that lists trials that are currently open for patient participation. The web address is www.cancer.gov/clinicaltrials or the telephone number is 1-800-422-6237. Many major sarcoma centers have the trials that are open for participants listed at their institutional website. Healthcare providers may have information about studies being conducted at other sarcoma centers as well as patient advocacy groups may be a helpful resource for locating clinical trials.
	Second, it is important to consider the impact participating in a clinical trial will have on one’s personal life, such as the time requirement, travel and expense. Discussing the potential impact with family and friends can help a patient and family be prepared.
	Third, it is helpful to know and understand what the trial is about. Asking questions and understanding your rights as a trial participant is imperative. It is important to understand that a person may withdraw from a clinical trial if at anytime they feel it is no longer in their best interest to participate. The more knowledge one has can lead to a more confident decision.
	Finally, it is important that an individual decide what is best for them. One can consult with family and friends but ultimately it is the decision of the individual.

Clinical trials provide valuable new options for treatment in the fight for a cure. The best way to determine effective new treatments is through systematic evaluation done within clinical trials.

Clinical Trials from a Participant's Perspective

Peaks, Potholes & Paralyses

Marcia E. Baker, D.O., FACOI

Grosse Point, Michigan

Living inside a clinical trial is a journey of peaks and potholes. Peaks are easy. The highest is waking up alive. Potholes litter the path too and are usually annoyances or inconveniences. When they occur, I try to remember what G. K. Chesterton said, “An inconvenience is an adventure wrongly considered.”

The busy ER provided one such recent adventure. Sick babies, strokes, motor vehicle accidents, and traumas from the nearby tornado hit to a motor home park filled the nooks and crannies of a small town in southwestern Missouri in January. When CODE BLUE was announced overhead, my first impulse was to rush to Room 214 and save the day. Then I remembered I hadn’t saved anyone’s day for eighteen months when metastatic leiomyosarcoma caused me to leave my beloved internal medicine practice. I was in the ER not as a physician but as a cancer patient whose oncologist had referred for evaluation of a suspected deep vein thrombosis (DVT). My port used for chemo was inflamed and tender. After twelve hours of waiting for the true emergencies to be seen, I was told the Doppler was negative and released.

The deepest pothole in my journey came with the news that without chemo I had less than a year to live. My options included several unappealing traditional chemo regimen and ET-743, a promising drug available only via clinical trial in limited supply in only a few sites across the country. Through the intervention of my oncology team, I was referred to another center for consideration of an expanded access clinical trial. Five months into my clinical trial, I am filled with hope. My CT scans have demonstrated no progression of metastatic disease. Stable disease is considered a response.

Gratitude continues to be a constant companion that I have been given this chance to participate in this drug trial. Every day I live breeds hope that I will survive to benefit from advances in research that may bring more definitive treatment. In between the peaks of gratitude and hope exists the reality of traveling six hundred miles round trip for a 24-hour infusion of chemo every twenty-one days. Although my physical side effects are limited to annoying potholes of nausea, gastroesophageal reflux, constipation, anorexia, and fatigue, my mind and soul suffer more limiting blows. A life-suffocating fatigue breeds a mental paralysis that dulls my ability to experience pleasure, animation, or hope.

Fortunately, this paralyzing inertia lasts for only a week or so of the cycle. This shadow self is transient and precedes a rebirth of desire, joy, and hope. During these peaks I have enjoyed traveling to the Rocky Mountains, Greece, Grand Cayman, and spending more time with my family. There is nothing like the loss of vitality to make its return a cause for uninhibited celebration. Life is a gift. It is precious beyond description. I will be forever grateful for those who continue to do cancer research and champion the cause of those like me who depend on the kindness of strangers for our very life. 

Additional Considerations

The Liddy Shriver Sarcoma Initiative has an extensive set of abstracts of clinical trials on its website for sarcoma patients and clinicians to consider. Click here to view them. Here are some additional insights shared on the pages of the Liddy Shriver Sarcoma Initiative's clinical trial web pages.

Suppose you are going to visit with the team conducting the clinical trial to see if you are a candidate for it. Here are some suggestions about what you should bring to your first appointment with the clinical trial doctors. Your medical history. The more of your medical history the doctor has, the “better” the appointment might go. The medical history is used to determine if you can participate in the trial or not. Details of the chemotherapy drugs that you have had (which drugs, their frequency, dosing, etc), pathology reports, CT scans, MRI scans, and X-Rays can often be very useful to aid the medical staff in making this determination. Fill out as much of the paper work ahead of time as possible. Have your insurance company approve your participation and provide the cancer center with the appropriate approval information before your visit. Your questions about the clinical trial itself. What can you expect? What will be done, how often, when, and for how long? Under what set of circumstances would you not be allowed to continue on the clinical trial after you have started it? Since clinical trials involve the collection of research data for the oncologists and research staff, there are frequent blood tests (called "PK" studies, where PK = pharmacokinetic) which are collected over the first 2-3 cycles of the treatment. These PK studies normally have to be done at the cancer center where the clinical trial is being conducted Your questions about the drugs that will be used, their frequency, dosing, side effects, precautions, known results, etc. Your questions about the tests you’ll need and where they can be done. You may also have to undergo baseline and post treatment tests (e.g., CT scans, MRIs, PET scans, and/or X-Rays) as appropriate. These tests may or may not be able to be done elsewhere (e.g., near your home). Where these tests are done may be a consideration if the site conducting the clinical trial is relatively far from your home. You may need to plan to stay overnight near the cancer center depending on the location of the cancer center, how long the treatment takes, how long you are to be observed after the treatment, and when and where any after-treatment tests are scheduled. There are programs that might be able to help family with travel expenses associated with getting to and from cancer treatment centers (see the Sarcoma Post-It® Links note in the right hand column, above). Make sure when you call and make the appointment to get detailed directions to the cancer center facility, particularly if it is another city or state. When considering if a clinical trial is “worth” your time (in contrast to only “aiding science” by your participation in it), you probably want answers to a number of questions. You can get help in obtaining answers to your questions and in understanding the issues involved from establishing a relationship with the Research Assistant or Research Nurse associated with the clinical trial. Remember to do your research before applying for a clinical trial. Some sample questions for the Research Assistant or the Research Nurse are: Are there currently or have there been patients with my cancer on the trial? Known results? Are there currently or have there been similar trials elsewhere in the US or abroad? What was learned about dosing and types of cancer the drugs have been successful with in these trials? Is this a multi-center trial? Are there any results known from using the drugs in other centers? Has the protocol been used on a “compassionate use” basis? Compassionate use is discussed below. Making Your Decision Clinical trials are not only to be considered as third line options. Dr. Albritton once commented, “I think it’s important to understand when to consider what phase of a clinical trial might be appropriate for you. Sometimes untreated patients enter Phase III clinical trials. Indeed, at initial diagnosis of Ewing’s sarcoma, you would only want to consider a Phase III clinical trial. At first relapse or progression of the disease, you would want to consider Phase II trials that are specific to Ewing's sarcoma. Third line, you would want to consider phase II trials perhaps for all types of sarcoma or solid tumors. Fourth line, you would want to consider Phase I trials. If you have tried these other routes and have moved more to a mode of realizing there is unlikely to be a drug that will cure the disease, but still want to be getting a drug, and contributing to advancement of Ewing's treatments, this may be time for becoming involved in a Phase I trial.”.   In the end, you will contrast participation in the clinical trial with your other treatment options. Do the possible outcomes and risks seem acceptable to you and your cancer given the currently known results about the chemotherapy agents involved? How will your participation affect your ability to participate in future clinical trials involving the same or other drugs? Will there be some other, more appropriate or more interesting clinical trials that might be opening up soon? None of these are easy questions to answer. You will want to seek the advice of your oncologist and your family. If you do decide to enter a clinical trial, be prepared to complete additional forms and paperwork and to establish a specific schedule of visits for treatments and tests, so be sure to allow enough time and to bring your calendar with you to do this. We urge you to document your experience in as much detail as possible so that it can ultimately be of benefit to others.

Mini Glossary

Taken from NCI Dictionary of Cancer Terms

Clinical trial

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

Endpoint

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

Expanded access trial

A way to provide an investigational therapy to a patient who is not eligible to receive that therapy in a clinical trial, but who has a serious or life-threatening illness for which other treatments are not available. Expanded access allows a patient to receive promising but not yet fully studied or approved cancer therapies when no other treatment option exists. Also called compassionate use trial.

FDA

The Food and Drug Administration (FDA) is an agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The FDA also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe.

Investigator

A researcher in a clinical trial or clinical study.

IRB

A group of scientists, doctors, clergy, and consumers that reviews and approves the action plan for every clinical trial. There is an IRB at every health care facility that does clinical research. IRBs are designed to protect the people who take part in a clinical trial. They check to see that the trial is well designed, legal, ethical, does not involve unnecessary risks, and provides safeguards for patients. Also called Institutional Review Board.

Placebo

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Placebo therapy

An inactive treatment or procedure that is intended to mimic as closely as possible a therapy in a clinical trial. Also called sham therapy.

Placebo-controlled

Refers to a clinical study in which the control patients receive a placebo.

Protocol

An action plan for a clinical trial. The plan states what the study will do, how, and why. It explains how many people will be in it, who is eligible to participate, what study agents or other interventions they will be given, what tests they will receive and how often, and what information will be gathered.

Statistically Significant

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant. [Author's addition: Statistical significance is achieved when the results of a trial are deemed sufficiently reliable (not having occurred by chance) to support a given hypothesis.]

Additional Terms

EMEA

The European Medicines Agency (EMEA) is a decentralized body of the European Union with headquarters in London. Its main responsibility is the protection and promotion of public health, through the evaluation and supervision of medicines for human use.

Sponsor

Pharmaceutical companies, nonprofit organizations, or other institutes, the National Cancer Institute for example, may sponsor clinical trials. Pharmaceutical companies fund studies because they must prove their new medication or treatment is safe and effective via success in a clinical trial, in order for it to become available to the public.