If a clinical trial is open for your child’s particular type and stage of tumor, within days of diagnosis you will be asked to consider enrolling your child in it. You then must choose between the standard treatment and the clinical trial.
Clinical trials are carefully controlled research experiments that use human volunteers to develop better ways to prevent or cure diseases. Pediatric clinical trials attempt to improve upon existing treatments. A clinical trial can involve a totally new approach that seems promising, or it may fine-tune existing treatments by reducing their toxicity or developing new ways to assess responses to treatments. Many children are needed in each clinical trial for the results to be statistically meaningful.
In some cases, such as when a young child has Wilms tumor with favorable histology, the standard treatment has a high likelihood of resulting in complete and lasting cure. For other types of tumors, the prognosis may be poor on the standard treatment, and parents may be more motivated to choose a clinical trial. Occasionally, parents choose to enroll their child in a clinical trial because they want to contribute to better treatments in the future. Other parents may be wary of participating in an experimental program and may opt for standard treatment. There is no right choice. Obtain all the information you can, weigh the pros and cons, and make a decision based on your values and comfort level.
Your treatment team may also tell you about studies that are sponsored by pharmaceutical companies, especially those designed to support patients through the effects of treatment. Such supportive care trials evaluate antibiotics, antinausea drugs, and new agents to raise blood counts, minimize pain, or control other symptoms. The oversight and control of these trials is entirely different than the oncology treatment studies discussed in this chapter. Ask your doctor or nurse to discuss these studies with you if your child is invited to participate in one.
You also may be asked for permission to allow biological studies of your child’s tumor. These studies involve performing specific tests on pieces of your child’s tumor to help develop better treatments. The pediatric surgeon or pediatric oncologist may ask your permission to send any tumor left over after diagnosis to a tumor bank for research. Because solid tumors can have subtle differences (called subtypes), biological studies help researchers better identify and understand the subtypes. Scientists are also using banked tumor cells to test responses to new medications and immunotherapy.
Types of clinical trials
The three main types of clinical trials for children with solid tumors are described below.
• Phase I. Drug studies begin in laboratories, where the drugs are evaluated using chemical or biological models, tissue samples, and other methods to see whether there is a chance the drug might be effective at treating disease. If laboratory evidence suggests a drug may work in humans, it is first tested in a Phase I study. These studies examine how the body processes (metabolizes) the drug, establish the highest dose that can safely be given to a patient (the maximum tolerated dose, or MTD), and evaluate the side effects.
In pediatric Phase I trials, the dose of a new drug is gradually increased in small groups of children until it becomes too toxic; essentially, one small group of children gets a low dose, the next small group gets a slightly higher dose, and so on, until an unacceptable number of children experience unacceptable side effects.
Phase I studies are experiments, and their purpose is not to cure the participants. The true beneficiaries of Phase I studies are future patients. In most cases, parents are not asked to enroll their child in a Phase I study unless all other treatment options have failed. Parents often enroll their children in these trials in the hope that a new and untried drug will be effective against their child’s disease, but they need to recognize that the chances of achieving remission are low. Because they require careful monitoring, Phase I studies are only conducted in a select few hospitals.
• Phase II. Phase II trials refine the safety parameters and evaluate new drugs’ effects on specific tumors. This is the stage at which many drugs fail—meaning they are not as effective as originally predicted or they have unexpected or serious side effects. Occasionally, Phase II trials are designed to test an exceptionally promising agent against a tumor for which no effective therapies exist.
• Phase III trials. These clinical trials determine whether a new treatment is better than the standard therapy. Some Phase III trials are designed solely to improve survival; others are done to try to maintain survival rates while lowering the toxicity of treatment. In pediatric Phase III studies, some children will receive the standard therapy, while others receive a modified version. Modifications include higher or lower doses of medication or radiation, different combinations of drugs, or different types of surgery. Some children will derive direct benefit if a new treatment is superior to the standard therapy. Other children will receive the same therapy they would have received if not enrolled on the study (the standard arm). To ensure the results are accurate, Phase III studies require thousands of participants and take several years to complete.
The National Cancer Institute (NCI) offers several resources to help parents understand the clinical trial process. You can call the NCI at (800) 422-6237 or visit its clinical trials website at www.cancer.gov/clinical_trials.
The information in the rest of this chapter pertains to Phase III trials that are reviewed and funded by the NCI. Enrolling in Phase I and Phase II trials is very different, as is enrolling in trials sponsored by pharmaceutical companies.
Design of clinical trials
In 2000, four pediatric cancer research groups merged to form a single pediatric cancer research organization called the Children’s Oncology Group (COG), which is supported by NCI. Approximately 200 institutions that treat children with cancer are members of COG (www.childrensoncologygroup.org). Researchers from these institutions contribute to the design of new clinical trials for children with cancer. In addition, the NCI and some large children’s hospitals design their own clinical trials for children. When designing pediatric clinical trials, the first priority is to protect the children from harm. Researchers are ethically bound to offer treatments they think will be at least as safe and effective as the standard of care.
Phase III clinical trials sort participants into different groups (called arms) that receive different treatments. Every Phase III trial has one arm that is the current standard of care, called the standard arm. Each of the other arms contains one or more experimental components, such as the following:
• New drugs
• Old drugs used in a new way (e.g., different dose or new combinations of old drugs)
• Duration of treatment that is shorter or longer than standard care
• The addition, deletion, or change in dose of certain treatments (e.g., radiation therapy or surgery)
• The use of new supportive care interventions (e.g., preventative antibiotics or new drugs to control nausea)
Sean missed the deadline for enrolling in a clinical trial when he was diagnosed. However, when his tumor regrew we did enroll him on a trial. The particular trial he was in was a randomized computer trial that decided if he was getting one or two chemotherapy agents. We felt if we enrolled him in the trial, maybe the results would help other children.
Phase III trials require a process called randomization, meaning that after parents agree to enroll their child in a clinical trial, a computer randomly assigns the child to one arm of the study. The parents will not know which treatment their child will receive until the computer assigns one. The purpose of computer assignment is to ensure that children are evenly assigned to each arm without bias from physicians or families. One group of children (the control group) always receives the standard treatment to provide a basis for comparison to the experimental arms. At the time the clinical trial is designed, there is no conclusive evidence to indicate which arm will be superior. As a result, it is impossible to predict whether your child will benefit from participating in the study.
We had a hard time deciding whether to go with the standard treatment or to participate in the study. The “B” arm of the study seemed, on intuition, to be too harsh for her because she was so weak at the time. We finally did opt for the study, hoping we wouldn’t be randomized to “B.” We chose the study basically so that the computer could choose and we wouldn’t ever have to think “we should have gone with the study.” As it turned out, we were randomized to the standard arm, so we got what we wanted while still participating in the study.
Researchers closely monitor each ongoing clinical trial and modify it if one arm is identified as superior during the course of the trial or if an arm has unacceptable side effects.
Supervision of clinical trials
The ethical and legal codes governing medical practice also apply to clinical trials. In addition, most research is federally funded or regulated and has rules that protect patients. For example, all COG trials are federally funded and have review boards that meet at prearranged dates for the duration of each trial to ensure the risks of the trial are acceptable relative to the benefits.
The treating institution is required to report all adverse side effects to COG, which reports them to the U.S. Food and Drug Administration. If concerns are raised, the study may be put on hold while an independent Data Safety and Monitoring Board and the study committee review the situation. If one arm of the trial is causing unacceptable side effects, that arm is stopped, and the children enrolled are given the better treatment.
All institutions that conduct clinical trials also have an Institutional Review Board (IRB) that reviews and approves all research taking place there. The purpose of the IRB—made up of scientists, doctors, nurses, and citizens from the community—is to protect patients. Funding agencies (e.g., National Cancer Institute) also review and approve trials before children are enrolled.
Questions to ask about clinical trials
To fully understand the clinical trial proposed for your child, here are some important questions to ask the oncologist:
• What is the purpose of the study?
• Who is sponsoring the study? Who reviews it? How often is it reviewed? Who monitors patient safety?
• What tests and treatments will be done during the study? How do these differ from standard treatment?
• What are the possible benefits?
• What are all possible disadvantages?
• What are the possible side effects or risks of the study? What are the side effects of the study compared to those of standard treatment?
• How will the study affect my child’s daily life?
• What are the possible long-term impacts of the study compared with the standard treatment?
• How long will the study last? Is this shorter or longer than standard treatment?
• Will the study require more hospitalizations than standard treatment?
• Does the study include long-term follow-up care?
• Will you compare the study versus standard treatment in terms of possible outcomes, side effects, time involved, costs, and quality of life?
• Will our insurance cover the costs of the clinical trial?
After discussing the clinical trial with the oncologist, you will need a copy of the information to review later. Many parents record the coversation or bring a friend to take notes; others write down all the doctor’s answers for later reference.
Things to consider about clinical trials
A clinical trial involving very high-dose chemotherapy followed by stem cell transplant was proposed for our 2-year-old daughter. We asked numerous questions, and I wrote down all the answers in my notebook. The two primary questions were: How many kids die during and after this treatment? Are her chances of long-term survival worth the pain we were going to put her through? We struggled with the concept of hurting her if it wasn’t going to do any good. We also asked about the specific drugs, their side effects, and what to expect from each treatment. It was a very difficult process and decision.
Deciding whether to enroll your child in a clinical trial is often difficult. The following lists describe why some families choose to enroll and why others choose not to enroll. These lists may help clarify your feelings about this important decision.
Why some families choose to enroll:
• Children receive either state-of-the-art investigational therapy or the best standard therapy available.
• Clinical trials can provide an opportunity to benefit from a new therapy before it is widely available.
• Children enrolled in clinical trials may be monitored more frequently throughout treatment.
• Review boards of scientists oversee clinical trials.
• Participating in a clinical trial often makes parents feel they did everything medically possible for their child.
• Information gained from clinical trials will benefit children with cancer in the future.
Reasons why families choose not to enroll:
• The experimental arm may not provide treatment that is as effective as the standard, or it may cause additional side effects or risks.
• Some families do not like the feeling of not having control over choosing the child’s treatment.
• Some clinical trials require more hospitalizations, treatments, clinic visits, or tests that may be more painful than the standard treatment.
• Some families feel additional stress about which arm is the best treatment for their child.
• Insurance may not cover investigational studies. Parents need to carefully explore this issue prior to signing the consent form.
Before a child is enrolled in a clinical trial, the parents need to sign an informed consent form. True informed consent is a process, not merely an explanation and signing of documents. Informed consent requires that:
• All treatments available to the child have been explained—not just the treatment available at your hospital or through your doctor, but all the treatments that could be beneficial, wherever they are given.
• The parents and, to the extent possible, the child, have discussed these options and chosent the treatment they want.
• The option selected is thoroughly discussed, with all its benefits and risks clearly explained.
• Aspects of the study that are considered experimental and those that are standard are clearly described.
An informed medical decision is one that weighs the relative merits of a therapy after full disclosure of benefits, risks, and alternatives. During the discussions between the doctor(s) and family, all questions should be answered in language that is clearly understood by the parents and child or teen, and there should be no pressure on parents to enroll their child in a study. The objective of the informed consent process is that all family members are comfortable with their choice and can comply with it. Studies show that the more questions parents ask during the informed consent process, the better they understand what they are agreeing to.
We had many discussions with the staff prior to signing the informed consent to participate in the clinical trial. We asked innumerable questions, all of which were answered in a frank and honest manner. We felt that participating gave our child the best chance for a cure, and we felt good about increasing the knowledge that would help other children later.
Informed consent is a process that occurs over several meetings. During the meetings, the pediatric oncologist provides information and the parents ask questions (and get answers). However, the informed consent process does not always work as it should for a variety of reasons, including the parents’ state of mind, the communication style of the doctor, and the system in place to discuss treatment options. Usually, this situation is the result of miscommunication arising from some combination of the following:
• No formal meeting times were established in advance to discuss treatment options, so parents did not understand the importance of the discussion they were having with the doctor and the treatment team.
• Parents, who are tired, confused, and mentally numb, appear to understand things they are barely hearing.
• The doctor is unconsciously promoting the choice she believes is the best one and she interprets the lack of questions as agreement.
• There is no one in the room except the doctor and the parents; therefore, there is no one to help with communication.
It is a good idea to ask the treatment team immediately after diagnosis when and how the treatment decision will be made and to ask for specific meeting dates and times to discuss treatment, even if it means a slight delay before starting treatment. Parents may want to invite a trusted friend or their child’s pediatrician to attend this meeting to ensure they understand their options.
When my son was diagnosed, we were told we had two options: a clinical trial or standard treatment. We decided to get a second opinion before making our decision. Our pediatrician, my husband, and I met in the pediatrician’s office for a telephone conference with a pediatric oncologist from a major treatment center. We each presented our concerns. Our pediatrician thought of some issues neither my husband nor I had considered. I think we all came away better informed of our options.
Some families seek a second opinion to help sort out their options. It is most useful to get a second opinion from a center that treats significant numbers of patients with your child’s diagnosis. Most pediatric oncologists are willing to arrange the second opinion for you.
Studies have shown that when treatment team members who are not doctors are present during the informed consent meetings, parents have a better understanding of their choices. You may want to ask for a nurse or a social worker to be present during the meetings.
Two days after my child was diagnosed, the oncologist told me it was time to begin treatment. I do remember him talking a lot, but I swear it actually sounded like “Wah, wah, wah, protocol, wah, wah, wah, very successful, wah, wah, wah, sign here.” And I did. It was several days before it sank in that I had authorized an experimental treatment protocol and not the standard of care. The irony is that I worked in clinical research. I knew how this was supposed to go. But I was alone and tired and frightened and went along like a sheep. Did he railroad me? Maybe; but I don’t think he meant to and in the end it was my responsibility to hold it together and ask what needed to be asked. But it just wasn’t in me at the time. Later, I told the doctor this and he was astonished to learn that I hadn’t heard a word he said.
Assent means that children and adolescents are involved in decisions about their treatment. Children younger than age 18 do not have the legal right to refuse standard treatment for their cancer. They do, however, have the right to accept or reject experimental treatments. All clinical trials are considered to be experimental treatments. Regardless of whether children will receive the standard treatment or an experimental treatment, they have the right to have the disease, treatment, and procedures explained to them at an age-appropriate level.
Doctors and parents are required to allow children to make their wishes known about their treatment. According to the American Academy of Pediatrics (AAP), assent means that the child:
• Is aware of the nature of his or her disease.
• Understands what to expect from tests and treatments.
• Has had his or her understanding assessed.
• Has had an opportunity to accept or reject the proposed treatment.
Parents can read or download a copy of the AAP policy statement (“Informed Consent, Parental Permission, and Assent in Pediatric Practice”) from the APP website. In part, the policy states, “In situations in which the patient will have to receive medical care despite his or her objection, the patient should be told that fact and should not be deceived.” This policy applies to standard treatment.
Clinical trials, however, are research, and Internal Review Boards (IRBs) decide whether the child’s assent is necessary. If parents and the child or teen disagree about treatment, discussions are usually held with a mediator (for example, a social worker or pediatric psychologist) to try to reach an agreement. If parents and their child or teen still disagree, an advocate for the child is appointed and a decision about treatment is made by the hospital ethics committee.
In short, parents can legally make decisions about standard care, but both parents and children have decision-making rights about whether or not to participate in clinical trials.
Table of ContentsAll Guides
- 1. Diagnosis
- 2. Bone Sarcomas
- 3. Liver Cancers
- 4. Neuroblastoma
- 5. Retinoblastoma
- 6. Soft Tissue Sarcomas
- 7. Kidney Tumors
- 8. Telling Your Child and Others
- 9. Choosing a Treatment
- 10. Coping with Procedures
- 11. Forming a Partnership with the Medical Team
- 12. Hospitalization
- 13. Venous Catheters
- 14. Surgery
- 15. Chemotherapy
- 16. Common Side Effects of Treatment
- 17. Radiation Therapy
- 18. Stem Cell Transplantation
- 19. Siblings
- 20. Family and Friends
- 21. Communication and Behavior
- 22. School
- 23. Sources of Support
- 24. Nutrition
- 25. Medical and Financial Record-keeping
- 26. End of Treatment and Beyond
- 27. Recurrence
- 28. Death and Bereavement
- Appendix A. Blood Tests and What They Mean
- Appendix B. Resource Organizations
- Appendix C. Books, Websites, and Support Groups