Clinical Trials

Additional clinical trial resources

Is a clinical trial right for you?

Research has shown again and again that the best way to improve treatment is through the clinical trial process.  This process sets up a rigorous set of scientific questions and the criteria needed to answer them.

Clinical trials require resources, in the form of funding to run them, and patients to enroll in them.  Without patients willing to enroll on trials for new treatments, it isn’t possible to determine whether new treatments are indeed better than the current standard treatment.  And yet, less than 10 percent of adults with cancer enroll on clinical trials.  In contrast, up to 90 percent of children with cancer are routinely enrolled on clinical trials. This high participation rate undoubtedly has contributed to the substantial increase in childhood cancer survival rates over the last generation.

The low participation in adult clinical trials is so worrisome to cancer researchers that the National Cancer Institute (NCI) and the American Society of Clinical Oncologists (ASCO) held a symposium in 2010 to discuss ways to improve accrual to trials.

Considering that many sarcomas do not have standard treatments that work well, one would think that patients would be clamoring for clinical trials.  On the contrary, many sarcoma trials have closed without obtaining results due to low patient accrual. The many misconceptions about clinical trials are likely a contributing factor. Therefore, the Sarcoma Alliance is providing this information to help you determine if a clinical trial is right for you.

What are Clinical Trials?

Medical research is done through studies called clinical trials. The clinical trial process is conducted in steps, or phases, that are intended to identify treatments that will be effective while keeping patients safe.  Cancer clinical trials may be for new treatments, for new methods of screening or diagnosis, for new supportive care agents, or for quality of life and survivor issues.  The focus for the information presented here is mostly for TREATMENT TRIALS.

Trial Phase
Goal of Research
Patient Enrollment
Pre-Clinical•Test a new treatment in cell lines or animal models
•Establish Good Manufacturing Processes (GMPs)
•Make enough for human trials
•No people at this phase
•If the treatment does not work in the pre-clinical phase, it will not be carried forward to treat patients
Phase I•Test the safety of the treatment in humans
•Analyze how the treatment works and is metabolized in the body
•Secondary goal of effectiveness.
•Can test a brand new drug or a combination of established treatments
•Relatively small numbers of patients
•Patients may have exhausted other treatment methods first, or there is no known effective treatment.
Phase II•Tests how effective the new treatment is for a particular type of cancer or subtype of cancer (eg, sarcoma)
•Secondary goal of monitoring safety
•Relatively small numbers
•Patients usually have been treated previously
•If no efficacy here, treatment unlikely to be carried forward
Phase I/II or Pilot•Usually speeds up evaluation of an experimental agent
•Primary goal is how effective is the treatment
•Relatively small numbers
•Used for rarer cancers, often for childhood cancers where the agent has already gone through Phase I trials in adults
Phase III•Primary goal is to compare treatments, frequently a head-to-head comparison of the efficacy of a new treatment to a standard one
•Secondary goals of safety, side effects, dosages
•Requires a large number of patients
•Patients may be randomly assigned by computer to different treatment arms
Phase IV•This is usually after acceptance of a new treatment
•Looks at longer-term safety and side effects
•Large numbers
•Not often done for cancer treatments

FAQ:

What is the benefit to me to be treated on a clinical trial? There are several medical and psychological benefits of being on a clinical trial, including: you are being treated with the latest treatments; your physician will be following your progress more closely as clinical trials require more data collection; you will have the knowledge that you helped in the development of better treatments.

Should I ask my physician about applicable trials?  Yes!  You should always ask about any treatment options, whether or not they are clinical trials, and whether or not they are available at your doctor’s institution.  If you are seeing a sarcoma specialist, they may have several recommendations for trials.  The Sarcoma Alliance has a list of 20 questions to ask when deciding between treatment options. http://sarcomaalliance.org/what-you-need-to-know/becoming-an-expert/  Remember that for sarcomas, we recommend being treated by a sarcoma specialist. These physicians are most likely to know what treatment options, including trials, are available.

Should I do my own research into available clinical trials?  Certainly, if you want to.  Two very useful sources of clinical trial information are on the National Institutes of Health website, www.clinicaltrials.gov, and the National Cancer Institute website, www.cancer.gov.  These websites can be searched using a number of criteria such as type of cancer, location of trial, and treatment agent. They list trials throughout the world that are run by public and private sponsors, and indicate if they are actively enrolling patients.  The information on them may be a little out of date, but this is an excellent way to start the search for trials.

Are clinical trials only options of last resort?  No!  As indicated above, clinical trials come in many phases. For example Phase III trials test which is more effective, a new treatment that has shown efficacy (in a phase I and II clinical trial) or an older treatment (that has already been approved because it was shown to be effective by an older clinical trial). Although Phase I trials are sometimes last options, they may be first-line treatments if no effective therapy is known. And remember, every effective cancer drug was once in a Phase I clinical trial. 

Will my insurance pick up the cost of a clinical trial?  The cost to you of clinical trials is usually comparable to that of standard treatment.  Talk to your physician about potential costs. Your out-of-pocket costs for a clinical trial may be identical to those of standard treatment, but this can depend on what costs are being picked up by the trial sponsor and what will be covered by insurance. Also, be sure to contact your insurance provider regarding possible coverage for clinical trials under the new Affordable Care Act.   http://www.cancer.org/treatment/treatmentsandsideeffects/clinicaltrials/statelawsregardinginsurancecoverage/clinical-trials-state-laws-intro 

Does my doctor get paid if I participate in a trial? Clinical trials cost money to run, as additional tests and data collection can be costly.  Usually, the institution that your physician works for is compensated to cover these additional expenses. Ask your doctor about this, or visit http://www.cms.gov/Regulations-and-Guidance/Legislation/National-Physician-Payment-Transparency-Program/index.html.

Will I have to travel to participate in a clinical trial? Access to trials may be limited by the need to travel to the specific locations where the trials are being held.  Some trials are likely to be at only one or a few locations; others, particularly Phase III trials, are likely to be held in numerous locations. Travel may add to out-of-pocket costs, but some organizations help defray travel costs, for example see the list of organizations that Sarcoma Alliance has compiled (http://sarcomaalliance.org/financial-assistance/). For some trials, you may be able to have most of the treatment and follow-up tests done near your home even if the official trial location is far away.

What is randomization, and can I avoid it? If a new treatment is being tested against an existing treatment, then patients will be assigned to either the old or the new treatment arm randomly by computer.  You will not be able to specifically choose the new treatment arm; the choice will have been made for you.  Remember there is no guarantee the new treatment will work better than, or even as well as, the standard treatment. Some trials will allow you to crossover between treatments if it appears that one arm is indeed doing better than another.    

What happens if I’m in the control group? The control group is the standard against which the outcome of a new treatment is measured. Many clinical trials will have a control group determined by randomization, and the control group receives the standard treatment.  Other trials, particularly for rare cancers, may use “historic” controls, in other words the results are compared to outcomes of previous studies with different treatments.  In general, using historic controls makes the best use of small number of eligible patients as everyone can be on the experimental arm.  However this isn’t the preferred way to control an experiment; for example, due to newer diagnostic methods, the disease stage or subtype of the present and historic patient groups might not be identical.

Could I wind up receiving a placebo (sugar pill) instead of treatment?  Cancer trials sometimes use a placebo as one of the randomized arms for cancer treatment.  One case where a placebo might be used is if “watch and wait” is the standard treatment. In other words, if no chemotherapy drugs would be used as the standard treatment compared to a new drug treatment, a placebo might be given so that both arms are “doing something” (basically, that’s the placebo effect).  Another case is where a new drug is being added to a standard treatment, and in order to “blind” the treatment arms (so that no one knows which is which) a placebo is added to the standard treatment.  In addition, a placebo might be used to compare a new drug that is intended to control side effects.

How would I know if I could get a placebo? When considering a trial, ask your doctor what exactly the treatment arms would include. Also read the informed consent information that you would be given before signing up for the study.  Feel free to ask why the placebo is included if indeed one is in the trial.

Why are some trials “blinded”? Blinding is used if it is important that the patient or doctor does not know which treatment arm is which.  Blinding is often used when the trial is measuring something subjective (for example, how well does this drug suppress nausea). It is also used for some targeted cancer treatments. Unlike traditional cytotoxic chemotherapy treatments for which efficacy is measured by tumor shrinkage, targeted treatments may stop tumors from growing but not make them shrink.  Thus, time to progression (the time it takes for a tumor to start growing again) could be the measured outcome.  Time to progression may be difficult to judge objectively, and blinding is likely to result in more objective determinations of if and when there is progression.

Are clinical trials as safe as standard treatments?  There is always the potential for some risk with new treatments, but that risk is minimized with the phases of the clinical trial process, which examine safety of a drug before efficacy.  Usually, trials monitor treatment effectiveness and side effects more often and sometimes in greater depth than standard treatments.  In addition, rigorous regulations control the process of approving research studies on people. 

How do I sign up for a trial? All trials will have a form called an “informed consent” for you to read and discuss with your doctor before agreeing to a trial.  The informed consent will include information on why the treatment is being tested, what the treatment entails, potential risks from the treatment, requirements for tests that are specific to the research questions asked rather than treatment, potential cost to you, and other information that is important for you to know before you agree to participate.  The informed consent should be written in non-technical language, rather than medical jargon.  Discuss your options thoroughly with your doctor, and ask questions if you don’t understand anything.

What is a trial protocol?  The protocol for the trial spells out exactly what the rationale for the trial is, including why the new treatment should be of value and what scientific questions are being asked; what the treatment regimens are; what tests and data will be collected during the trial and when they will be collected; and what follow up tests are needed after the treatment is complete.  In most cases your doctor should be able to provide you with a copy of the protocol, although unlike the informed consent it will be written in very technical language.

Can I opt out of a trial after I’ve signed up for itAbsolutely. You always have the right to leave a clinical trial at any time, for any reason.

Eligibility:

In addition to location or cost limitations, eligibility may restrict a patient’s access to a particular clinical trial.  The specific trial information on www.clinicaltrials.gov and www.cancer.gov always includes eligibility and exclusion criteria, but it might not always be obvious why there are certain exclusions.

Some common types of exclusion criteria you might see include items such as:

  • Prior therapy with the treatment agents (chemo, radiation).  It makes sense to exclude patients whose tumors haven’t responded to some of the treatment agents, and some drugs even have a maximum safe dose that has been reached already.
  • Serious side effects from prior treatment, such as cardiomyopathy (heart damage)Until shown otherwise, there is always the concern that new treatment agents might make the condition worse.  
  • Prior cancer treatment within a short time frameSince cancer treatments can take a few weeks or even more time to show responses, it might not be possible to determine if the previous treatment or the experimental one was responsible for a response.
  • No measurable tumors.  Most trials are set up to measure tumor shrinkage, or time to tumor size progression, as a result of treatment. Thus if tumors cannot be measured (as is the case for some types of metastases), it isn’t possible to determine if the treatment worked.
  • Central nervous system involvementBecause many of the drugs used to treat sarcomas are thought to not cross from the bloodstream into the brain or spinal cord (the blood-brain barrier), metastases in the central nervous system may make a patient ineligible for a trial.
  • Females who are pregnant or breast-feedingExperimental cancer treatments are never assumed to be safe for developing babies, as they are usually intended to stop cell division or kill cells outright.
  • Active infections.  Most anti-cancer treatment agents suppress the immune system, so having an active infection at the start of treatment could be very dangerous.
  • Other medical conditions that could affect the health of the patient. If your physician feels that your health could be compromised if you were on the trial due to other medical conditions you have, you should not be enrolled on it.

 

Sponsors:

Trials can be sponsored by a variety of institutions.

Government.  In the U.S., agencies such as the National Cancer Institute and other agencies fund cancer clinical trials.  These trials may be located at just the institution, or could be located at several locations.

Cooperative Groups.  These groups are consortiums of hospitals that specialize in doing research on cancer.  They are usually funded mostly by government agencies.  The benefit of cooperative groups is the ability to combine resources, particularly patient numbers, to get faster answers to research questions.  Of all the types of sponsors, Cooperative Groups are likely to have the most locations at which a trial is open.  Sarcoma Alliance for Research Collaboration (SARC) and Children’s Oncology Group (COG) are examples of cooperative groups.

Single Institution. These are universities and hospitals that set up their own trials.  These institutions usually have a large enough patient population to have good accrual rates to the trial.  Sometimes, several institutions will band together to form a multi-site trial that can get accrual and thus answers faster.

Individual.  These are specialist physicians who have a research interest and a large enough patient population to set up a trial and get results within a reasonable time frame.

Companies.  Companies sponsor clinical trials to show that their new treatment agent works better than existing treatments, which allows them to get approval for their agent.  They often will do the trial in coordination with a cooperative group, institutions, or individuals who are the ones who see the patients.

Results:

How often are results checked? Clinical trial data is checked for safety frequently while the trial is running by a monitoring committee made up of people who are not otherwise involved in the study.  If any safety problems arise during the review of data, the trial could be stopped or modified to protect people. Similarly, if it appears that one arm of a randomized trial is doing much better than another arm, the trial would be stopped.  Except for these safety conditions, outcome data usually will not be analyzed until the trial has closed to accrual.

How are results used? The clinical trial has a protocol that spells out what scientific questions are being asked, and the results will be analyzed statistically to determine whether the study answered the questions in a positive way (for example, the new treatment is better) or negative way (we couldn’t show that the new treatment was better).

Will I find out the results?  In general, yes, although it might take several years depending on how long the trial is open, and how long patients are being followed after the trial ends. There has been a big push to get results back to trial participants, and more and more physicians are making efforts to do that.  The National Cancer Institute requires that federally funded trial results be published within a certain time frame. Check if the informed consent has information on whether you will receive results, and talk to your doctor if you have any questions.

Summary of Pros and Cons of Clinical Trials

Trial Feature
Pros
Cons
CostCost may be completely covered by the sponsor.If cost isn’t completely covered, insurance may not pay for all trial costs (although this is rare).
LocationsThe trial is likely to be done by specialists or at specialist institutions where you can get the best care.You may have to travel for at least part of the treatment.
Medical TestsYou will be more closely followed by your oncologist than if you are on a standard treatment, which can provide better information on how well the treatment is doing as well as controlling side effects.You may need to do more doctor visits and more types of tests than with a standard treatment.
RandomizationRandomized trials are designed to have “equipoise”: in other words, there isn’t an expectation at the start that either treatment is better than the other.You might not get the experimental treatment, and it could turn out that the treatment you received, experimental or standard, was not the superior arm.
Involvement in TreatmentParticipants have made an active choice in their treatment and are often more aware of their options.Randomization may make some people feel that they have less control over their treatment.
EfficacyYou will be getting at least the standard treatment, and may be getting a better treatment.The trial may not benefit you personally.
Helping OthersClinical trials are the best way to improve treatment for people diagnosed with sarcoma in the future.There is no downside to helping others; remember that if a treatment works now, it is because previous patients enrolled in past clinical trials.