Clinical Trials

Ewing's Treatments

Cancer-Related Clinical Trials

The following article appeared in the February 2004 issue of the ESUN newsletter.

by Liddy Shriver and Bruce Shriver

In this issue of ESUN, we will briefly discuss how clinical trials may fit into your treatment plan.

First Line Treatments

The treatment for Ewing's sarcoma, like the disease itself, is aggressive. The first line treatment is often 9-12 months long and can consist of 10-14 cycles of chemotherapy, resection surgery to remove the primary tumor, and radiation to the resection site. The drugs used differ a bit depending on the specific protocol the doctor is following. Quite often the first line treatment consists of cycles of vincristine, Adriamycin, and cyclophosfamide alternated with cycles of etoposide and ifosfamide. These and other chemotherapy agents will be discussed in the Drug News section of ESUN. Baseline scans (e.g., CT, MRI, PET, and X-Rays) and baseline blood work is done at the beginning of the treatment regimen. Additional blood work is done after each cycle or two in order to monitor the patient’s response to the chemotherapy agents and to see if the treatment should currently be continued (e.g., to see if your blood counts are high enough for you to continue with the drugs at the current time).

Second Line Treatments

The response of your tumor to the chemotherapy might be able to be seen after 2-4 cycles of chemotherapy by scanning the primary tumor and other areas of your body and comparing the results to your baseline scans for primary tumor growth and for the development of metastatic sites (i.e., indications that your cancer is spreading to other sites). If the first line treatment isn't successful, the chemotherapy regimen is frequently changed to another protocol. There is no particular regimen that all or most oncologists use for the second line treatment of Ewing’s sarcoma at this time. A number of the alternative regimens have been shown to be equally as good as one another. If your tumor appears to be stable (i.e., it responds to a chemotherapy regimen and your cancer has not spread), surgery may be considered for a second line treatment if it was not employed earlier. If your tumor responds to a specific chemotherapy regimen but your cancer has metastasized, your oncologist might recommend that you have stem cells drawn to give you the option of using “high-dose” chemotherapy with stem cell transplant. High dose chemotherapy with stem cell transplant is a very demanding but potential treatment to be considered for metastatic disease.

Clinical Trials

If the cancer fails to respond to the first and second line treatments, you may turn to clinical trials. A “clinical trial” is a well-planned research study that tests a drug or treatment method to see how well it works on people. In the US, clinical trials are overseen by the Food and Drug Administration. They are typically carried out in a cancer clinic, institute, center, or other medical facility under the control of a medical team. Clinical trials involve rigorous testing, reporting and adherence to specific guidelines. Not all patients are eligible to be involved in a clinical trial, even if it includes the specific cancer they have. There are constraints that might make you ineligible to participate in a specific clinical trial, e.g., your age, your previous chemotherapy regimens, and whether or not your cancer has metastasized.

What are the Different Phases of a Clinical Trial?

There can be up to four phases of a clinical trial.

Phase I: A Phase I Clinical Trial tests the safety, dosage levels, and response of a disease to a new drug or treatment method. Phase I Clinical Trials enroll a small number of patients, sometimes less than a dozen.

Phase II: A Phase II Clinical Trial tests if the new drug or method of treatment has an anti-cancer effect (e.g., if it shrinks a tumor, improves blood test results) and whether it works against one or more specific types of cancers.

Phase III: In a Phase III Clinical Trial, the results of people taking a new drug or using a new method are compared with results of people receiving an existing standard treatment. The comparison might include, for example, which group has better survival rates or fewer side effects from the drug or treatment method. Drug and treatment method studies enter a Phase III Clinical Trial only if a drug or treatment method seems to work in Phase I and Phase II Clinical Trials. Phase III trials may include hundreds of people at many clinics and cancer centers nationwide.

Phase IV: This phase evaluates the side effects of a new drug or treatment method that were not apparent in the Phase III Clinical Trial once a treatment has been approved and is being marketed. This phase may involve thousands of people.

Considering and Applying for Clinical Trials

There are a number of sources where you can learn of candidate clinical trials—e.g., from a member of your medical team, from the professional and lay literature, and from searching appropriate websites (see, e.g., the Clinical Trials section of the links page on our website). Clinical trials may involve a variety of different approaches in dealing with cancer; among them are using new drugs, new combinations of existing drugs, new protocols for administering drugs (e.g., different dosing and/or cycle lengths, i.e., “time compression” treatments), new combinations of chemotherapy and radiation therapy, and employing new methods for dealing with cancer (for example, investigating one of the two main immunotherapy approaches, antibody therapy and vaccine therapy). Once you have identified one or more candidate clinical trials—ones that deal with your cancer and for which you meet the eligibility requirements—we recommend that you do your research on the chemotherapy agents, protocols, and/or methods involved and then discuss them and the clinical trials with your oncologist.

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 as possible of time. 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. 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

We note that clinical trials are not only to be considered as third line options. Dr. Albritton recently told us that, “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-comer" 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. We urge you to document your experience in as much detail as possible so that it can ultimately be of benefit to others (see, e.g., our Anecdotal Database project).

Beyond Clinical Trials

Even if you can participate in a clinical trial, it might not be your best course of action. For example, participation at the beginning of a Phase I trial where the amount of chemotherapy received is very small, might have the effect of reducing your eligibility to be considered as a candidate in a future clinical trial. If a Phase I trial is the only current clinical trial option, it might be better to wait for another trial, or to try a chemotherapy agent off-study or in a “compassionate use” context. After a successful clinical trial, the FDA approves a drug for use for one or more cancers. “Off-study” refers to using an FDA approved drug for a cancer other than those for which it was approved. A patient with advanced disease or with no approved treatment or clinical trial options can attempt to get access to a new, unapproved drug outside of participating in a clinical trial. Access to a drug outside of a clinical trial prior to FDA approval is commonly referred to as “compassionate use”. We will discuss compassionate use in more depth in one of our upcoming issues. Useful link: The Cure Our Children Foundation’s new drugs, therapies and clinical trials page.

A "clinical trial" is a well-planned research study (investigation) that tests a drug or treatment method to see how well it works on people. In the US, clinical trials are overseen by the Food and Drug Administration. They are typically carried out in a cancer clinic, institute, center, or other medical facility under the control of a medical team. Clinical trials involve rigorous testing and reporting. Not all patients are eligible to be involved in a clinical trial even if it is involved with the cancer that they have. There are constraints that might make them ineligible to participate, e.g., their age, their previous chemotherapy regimens, and whether or not their cancer has metastasized. There can be up to four "phases" in a drug or treatment method study.

This is the end of the ESUN article.

There is a Lack of Young Adults in Trials

Here are some observations about this phenomena:

Young adults are different biologically than children and may might need different treatments.
Young adults often delay in seeking medical attention. Some feel that they are invincible while others are not covered by medical insurance.
Young adults get different cancers than other age groups; over 50% of the cancers are "pediatric", yet the oncologists are adult. For example, adult oncologists may be less willing to be aggressive with dosing that can be tolerated by the younger patient.
About 50% of children with cancer participate in trials; less than 1% of young adults do.

90% of children with cancer receive care at an institution which participates in NCI-sponsored trials; in the 20-to-29-year olds, this is only 10%.

There are fewer clinical trials for young adults.
Young adults are unwilling to participate in clinical trials.

The relative improvement in the survival rate in young adults has not kept pace with that achieved in younger patients. There may be a correlation between the lack of young adults and this lack of improvement in the survival rate.

Links to Locate Clinical Trials

See the Clinical Trials section of the links page on our website.