What is a Clinical Trial?

A clinical trial is a well-planned research study that tests a drug or treatment to see how well it works on people. In the United States, clinical trials are overseen by the Food and Drug Administration. They are typically carried out in a cancer center, institute, clinic, or other medical facility under the control of a medical team. Clinical trials may involve a variety of different approaches in dealing with cancer. These approaches can include:

• using new drugs
• using new combinations of existing drugs
• using new protocols for administering drugs (for example: different dosing and/or cycle lengths)
• new combinations of chemotherapy and radiation therapy
• employing new methods for dealing with cancer (for example: investigating one of the two main immunotherapy approaches, antibody therapy and vaccine therapy)

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 Clinical Trials?

from "Clinical Trials in Bone Sarcomas" in ESUN V3N2

Clinical trials are generally described as being conducted in a series of phases, I through III. The various phases represent, in order, the steps that a new drug needs to take in order to become approved as a standard treatment. In general, from the standpoint of a patient, their interest would be best served by being treated in the opposite order of that taken by drugs, so that they receive the most proven therapy possible for their tumor. Therefore, in considering participation in a clinical trial, first preference would generally be given to a phase III study.

Most phase III studies are performed in patients with newly diagnosed tumors, in which a standard treatment exists. Although study designs vary, in general, in a phase III study a randomized comparison is being made between treatment that is considered standard and an experimental arm which is hypothesized to be superior to that treatment. Although the experimental arm is hypothesized to be superior, that may not prove to be the case, hence the arms are viewed by the treating physicians as being equivalent. This equivalence is necessary to ethically be able to subject a patient to their treatment being decided randomly. In a well designed phase III study, the standard arm would be the treatment used by the majority of physicians for patients who did not elect to be part of the phase III study. The experimental arm would test something new and promising. In designing a clinical study the number of patients that will be permitted to participate is specified initially. The size of the study is defined so that it is likely to answer the question that is being asked. The parameters that influence the size of the study include the predicted outcome of the patients and the magnitude of the difference the intervention is believed possible of making, among others. The smaller the magnitude of difference anticipated, the larger the number of patients that are necessary for the clinical trial. In phase III studies a comparison is being made between a proven therapy and something which is postulated to provide an incremental benefit, hence by definition, the anticipated difference in outcomes for the treatment arms can not be large. Phase III studies therefore require large numbers of patients and because of the rarity of bone sarcomas necessitate their conduct as part of multi-institutional or cooperative groups over several years. Their performance in this manner mandates review by a large number of institutions and regulatory bodies, ensuring a high level of consideration of patient protection and safety.

Phase II trials are intended to obtain information on the efficacy of a new agent or treatment regimen. Of the three phases of clinical trials the greatest variability exists in the design of phase II studies, as multiple approaches can be utilized to obtain information on efficacy. In the most traditional phase II study design, a new treatment is given as a single therapy to a patient for whom no standard therapy exists. Typically this occurs in the setting of diseases that have recurred after standard therapy. The lack of standard therapy makes use of novel agents or treatment approaches ethically acceptable providing a treatment option, that otherwise would not have existed. In this setting, patients typically have a poor prognosis and therefore the likelihood that a new agent will prove to be effective is low. Phase II trials are also performed of new treatment regimens to pilot their feasibility and obtain a preliminary estimate of their efficacy. These pilot studies can be performed in different patient groups and are conducted for a variety of reasons. Some pilot phase II studies are conducted to demonstrate the feasibility of a regimen that is believed to be more efficacious than standard therapy, in anticipation of it becoming the experimental arm of a phase III study. In many of these studies, standard therapy is felt in some way to be inadequate justifying the use of a new treatment approach. These pilot phase II studies may be conducted in newly diagnosed patients, sometimes selecting patient subgroups which may be anticipated to have a worse prognosis, such as those presenting with metastatic disease. Numerous other phase II trial designs exist including window studies and randomized trials, a full description of which would be beyond the scope possible in this review. As these studies typically are not comparing treatments, these studies are typically smaller and therefore can be performed by single institutions as well as larger groups. It is not uncommon that a single patient may be eligible for more than one phase II trial. Frequently little data exists to provide a rational basis for selecting treatment on a particular phase II trial over other phase II trials or standard therapy. A treating oncologist can usually obtain additional information from the physicians leading each of the clinical trials among other sources and therefore is an invaluable resource in making these decisions.

Phase I trials are intended to demonstrate the safety of a new therapy or combination of therapies. These studies are virtually always performed in patients who have exhausted standard treatment options with alternatives to this therapy usually being other phase I trials or symptom directed care. Most phase I studies are performed with successive small groups of patients being treated at increasing doses to define what side effects occur and at what dose level. Given the nature of the patients being treated and that a proportion of patients will not be treated at the optimal dose of the new agent, the probability of having a response is relatively low, although a theoretical potential for benefit does exist. Similar to phase II trials, patients may be eligible for more than one trial and selecting between them is frequently difficult.

More Information About Clinical Trial Phases
* From SARC
* From M.D. Anderson Cancer Center

What Are the Different Types of Clinical Trials?

from the Sarcoma Alliance for Research Through Collaboration

Prevention Trials
These studies study better ways to prevent disease in people who have never had the disease or to prevent recurrance. These approaches may not involve only medicines or vaccines, but perhaps lifestyle changes, vitamins or minerals.

Early detection/screening trials
This type discovers ways to find or detect early stages of the illness.

Diagnostic trials
These trials discover innovative and improved methods to determine if someone has cancer – and if so, the location of the tumor, how much cancer is actually present, and whether it has metastasized to other parts of the body.

Treatment trials
These trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.

Quality of life/supportive care trials
This type seeks to improve the comfort and quality of life for patients and their families, or find advancements in palliative care.

 

Clinical Trials Key Terms

from the Sarcoma Alliance for Research Through Collaboration

General Terms

Trial Sponsors/Supporter: 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.

Protocol: A protocol is a detailed plan that explains what will be done in a clinical trial and why. It outlines things like the trial objectives, the PI's name and affiliated institution, how many patients will take part in the clinical trial, inclusion and exclusion criteria for participation, what medical tests patients will need to complete and how often, and the overall treatment plan. Before a protocol can be made available to patients, an institutional review board (IRB) must review and approve the study.

The Institutional Review Board (IRB): These boards consist of a committee of people, such as scientists, doctors, social workers, nurses, attorneys and patients, who are responsible for making sure that the trials follow federal laws to protect the rights of the clinical trial's participants. Before a trial begins, the IRB reviews and approves the protocol (sometimes altering or amending it) to make certain it is based on reliable scientific evidence and will not be harmful to the patient. After a clinical trial begins, the IRB monitors the trials - and reviews its progress, usually at least once a year. If any concerns about the saftey of participating patients arise throughout the process, the board can and will call a hault to the trial.

The Office for Human Resources Protections (OHRP) is part of the US Department of Health and Human Services. The primary objective of the office is to ensure patient safety and welfare in federally funded clinical trials. The OHRP guides the IRBs and helps enforce protective regulations.

Terms describing patient response

Response to treatment in a clinical trial can be described in the following terms:

Stable disease: A doctor may use the term “controlled” or “stable disease” if your tests or scans show a situation that remains unchanged over time. These terms mean that the tumor is showing no significant growth or decrease in size (that is, there maybe some growth or reduction but not enough to be categorized as a partial response or progressive disease). Some tumors can stay the same for a long period of time due to treatment, but some remain stable without any treatment.

Progressive disease: In clinical trials if the cancer does grow, it is deemed “progressive disease.” Most clinical trials define a tumor as a progressive tumor when there is a 20-25% measured growth in the tumor (although this also is specific to the clinical trial you are participating in). Tumor growth means that the tumor is getting bigger, but it may also mean that the tumor is spreading. Progression generally indicates that treatment has stopped working. The bottom line is that your cancer is not getting better.

Refractory cancer: For many reasons, cancer may not respond (or is thought to be resistant) to treatment. Some cancer cells have ways of defending themselves against many different types of therapies, termed refractory disease.Refractory cancer may shrink, but not to the point where the treatment is determined to be effective. Most of the time, this type of tumor will remain stable or continue to grow despite the treatments administered.

Complete Response: Doctors describe a complete response to treatment as that which completely gets rid of all tumors that were able to be measured on various tests. It may also be referred to as remission. After your cancer has been treated, your doctor will do some tests to see if any cancer cells are still present in your body. If your doctor can't find any cancer cells over a specified amount of time, you are thought to be in remission.

Partial Response: A partial response means your cancer responded and there has been a decrease in tumor size to some extent, but not completely, to your cancer treatment. If you are in a clinical trial this usually is defined more precisely, according to the parameters set forth in the protocol. A partial response is usually defined as a less than 50% reduction in measurable tumor, but in other trials a reduction in tumor size of at least 30% may be defined as a partial response.

More Clinical Trials Terms
* Glossary of Clinical Trials Terms from ClinicalTrials.gov

"Types of Clinical Trials" and "Clinical Trials Key Terms" © Sarcoma Alliance for Collaboration
Additional Content ©Liddy Shriver Sarcoma Initiative

When to Consider Clinical Trials

Clinical trials may be worth considering at different times when dealing with sarcoma. Dr. Karen 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.

Choosing a Clinical Trial

There are a number of sources where you can learn about candidate clinical trials: from a member of your medical team, from the professional and lay literature, and from searching appropriate websites.

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 by 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?

See "Participating in a Trial: Questions to Ask Your Doctor" from the National Cancer Institute

Visiting the Clincial Trial Physician or Team

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. 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.
  
  

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.

Off-Study

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.

Compassionate Use

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. See the following resources:

• Compassionate Use from CancerActionNow
• Compassionate Drug Use from the American Cancer Society
• The Abigail Alliance: working for better access to developmental drugs

 

Searching for Clinical Trials

The search for a clinical trial usually involves several steps. To get started, simply search for trials that involve a specific type of sarcoma. Your search will yield targeted clinical trials for that particular disease. Most of these studies will be in Phase II or III.

Click on a term below to view open trials for a specific type of sarcoma at ClinicalTrials.gov. Results will include clinical trials in all locations. To limit your search to a specific country or state, click "refine search" and scroll down to choose locations.

Alveolar Soft Part Sarcoma | Angiosarcoma | Clear Cell Sarcoma | Chondrosarcoma | Chordoma | Ewing's sarcoma | Fibrosarcoma | GIST | Leiomyosarcoma | Liposarcoma | Malignant Fibrous Histiocytoma | Mesenchymal Chondrosarcoma | Malignant Peripheral Nerve Sheath Tumor | Osteosarcoma | Rhabdomyosarcoma | Synovial Sarcoma

Broadening your search

Some clinical trial descriptions do not include specific types of sarcoma; they use more general terms instead. In order to explore all trial options, you will need to expand to an advanced search that includes broad terms that apply to your situation, like:

• sarcoma
• bone tumors
• solid tumors (these trials often include soft tissue and bone tumors)
• sarcoma AND metastasis
• sarcoma AND recurrent
• sarcoma AND unresectable
• pediatric sarcoma OR childhood sarcoma