Therapeutic Trials
In most cases, when a child is managed at the IHOPE, a standard treatment is already on-going to give more chance of recovery with the minimum side effects, in the current state of knowledge. These treatments are often endorsed by scientific societies (SFCE: French Society of children cancer, SIOP international Society of pediatric oncology…) and used by all French even European or international pediatric centres.
What is a therapeutic trial?
- Phase III trials:
They are comparative trials. These randomized trials aim at comparing a standard treatment with an innovative treatment. Since neither the caregivers, nor the experts know whether the innovative treatment is better than the standard one in terms of efficiency and tolerance, a randomized assignment is proposed to the parents and the child. An allocation performed by random software only can guarantee that the two groups of treatment are similar. Neither you nor the physician takes the decision to assign the reference standard treatment or the innovative one to your child. This IT random drawing is often called randomization in English. You are not asked to choose between these two treatments, you are being asked to agree that random makes the decision between those two treatments. Don’t be disappointed if random chooses the standard treatment since no one knows whether the innovative treatment will be more or less efficient, more or less toxic. Parents and/or the child can refuse this random draw, the child will then receive the standard treatment.
Of note, these trials are rigorously regulated by the law, and especially by the law of 09/08/1964, also known as the Huriet Serusclat law.
There is not placebo treatment for children, a treatment which is most likely efficient is thus used.
- Phase II trials:
A new treatment is offered to your child because the standard treatment is not 100% efficient. These trials are usually proposed for a relapse, or when the disease response is low. Inclusion criteria are much regulated for the objective is to always protect your child’s interest and to prevent him from excessive risks.
A phase II trial aims at collecting information on the potential efficiency of a new treatment (a drug or a combination of drugs, or a treatment strategy). The treatment toxicity has already been assessed. Doctors expect it to be efficient for your particular child disease. The benefit expected is not certain: it is about controlling the disease or at least to slow down its progression and to reduce symptoms and signs. In the best case scenario, a complete or partial remission, for a variable time, even a complete recovery can be obtained.
These phase II trials can also be randomized: they are called phase II randomized trials.
- Phase I trials:
The objective is to assess the toxicity of a tested drug (or a combination of tested drugs) and thus tolerance of the organism to the treatment. Thus to define which dose in recommended.
Getting a benefit by controlling the disease is low however not hopeless. The IHOPE is authorized to perform this kind of trials for it is a member of the Innovative Treatment for Cancer in Childhood (ITCC). These trials may be open is other centres and if necessary, doctors from the IHOPE will take the decision to refer your child to these centres with no contest. .
These drugs have most of the time been already tested on adults. They are given straightaway to children at a potentially efficient dose. The dose increases by successive dose levels. The treatment may thus be available when the dose level is open, whereas sometimes it is necessary to wait for the dose level to be available when the immediate becoming of a sufficient number of children, treated with this dose, is studied before possibly moving on to the next dose level.
You can refuse to have your child participating to a phase I trial if you feel that risks are excessive compared to the expected benefit. The physician will then propose a treatment which aims at slowing down the disease or to treat symptoms like pain and discomfort as part of palliative cares.
Most of the time, there are open phase I trials in several worldwide hospitals. Inclusions stop when the number of children who could benefit from the trial is sufficient. Several trials can be open at the same time, often with specific inclusion criteria. Your child may have the possibility to be included in several trials and the choice between these trials will be discussed with you and your child. A child can benefit from several successive trials.
When do we propose a therapeutic trial to your child?
- On one hand because the standard treatment can be modified (to improve its efficiency and/or decrease its toxicity), you will be then proposed a comparative trial.
- On the other hand because the standard treatment is not as efficient as expected and doctors can propose a new treatment to try and increase the odds of recovery.
In both cases, decisions are made during Multidisciplinary Tumour Boards including sometimes other experts, from France or abroad.
If parents and/or the child refuse the inclusion in a therapeutic trial, the quality of cares will be the same; the child will receive the most adapted treatment according to his medical status after an informed discussion with the medical team.
The caregiver always cares about treating and relieving your child’s pain and discomfort symptoms. A therapeutic trial is a way to meet this requirement. Moreover, according to your child status and your personal and professional situation, a hospitalization at home can be considered.
How does this proposition take place?
Sometimes, trials are only available in other centres, some children can thus be transferred to the IHOPE, from other centres. Similarly, the IHOPE can sometimes refer children in another centre where the trial is available. This point will be discussed with you and your child.
To be included in one of these trials your child must comply with specific criteria, defined in the protocol (inclusion or eligibility criteria). You will be given some explanations and a document that you will read at your discretion. You will then be proposed to sign a document called Informed Consent Form. Next, some “screening” exams will be proposed (blood tests and/or various X-rays) to make sure you child is eligible. At this stage, we sometimes find out with the medical exam outcomes that your child can’t be included in the trial. When possible, another treatment will then be offered.
Information is an essential point for, according to the law, receiving an experimental treatment is a volunteer act which means the patient does understand consequences of his choice. This is why we talk about an Informed Consent Form.
Your child will never participate to a research without your written consent. You will have to sign a consent form. No one will pressure you to get your consent. Your refusal will not modify the quality of cares your child will receive. The law states you can cancel your consent whenever.
Inclusion of your child in a trial does not imply a salary or financial charges for you. Your child will be also informed according to his age. If he disagrees to participate to this trial, the law states that one cannot override his decision. If he is old enough he will be asked for his agreement, he can also, if he wishes so, ask to cancel his agreement: public health code Article L1122 – 2 states that “the underage child or protected adult must also give his consent if he can express his wish. One cannot override his refusal or the revocation of his consent”.
You will be asked to sign a consent form. This signature does not release, in no instance, the doctor from his responsibilities. The consent form indicates that you have been informed and that you agree to participate to this research. It indicated also that your child has been informed, by taking his age into consideration, and that he has not refused to participate to the trial. It recalls your rights, the confidentiality of data and that you can revoke you consent whenever. This consent form comes along with an information letter presenting the trial, the potential benefits and the risks when known, exams and screening that your child will have to go for to make sure he can participate to the trial.
Can a therapeutic trial be suspended?
A therapeutic trial can be suspended if the sponsor has enough information to come to the conclusion that this treatment is efficient or not, or because one treatment is better than the other or because the treatment is not tolerated by your child and the doctor will adapt his treatment. A trial can also be suspended if you or your child (if he is old enough) takes the decision. You can discontinue from a trial whenever you decide without any explanation. Specific procedures are planned when discontinuing a trial and there will be no consequence on the management quality of your child or on the rapport of trust builds up between the medical staff, your child and you.
The law states that if your child refuses to participate to this research, his choice is the most important. He can decide to discontinue from an on-going treatment.
Professionals working by your side during a therapeutic trial.
The investigator of a trial is a physician. It is the physician who takes care of your child or the physician who is in charge of the trial. He coordinates the trial; he is responsible for all its steps and for the good clinical practices regarding the biomedical research. He collects data. This data is anonymous. He is also in charge of adapting your child’s treatment jointly with the laboratory or other physicians. He agrees to inform the sponsor in case of serious adverse events. Regular meetings take place with the other centres to make sure no unexpected reactions occur: in these cases you would be informed and measures are taken at once to modify or suspend the trial if necessary.
All trial must have a sponsor who is a natural person or a company or an institution that initiates a biomedical research. This sponsor is accountable before the authorities for the trial and for the dissemination of information regarding the safety of people participating to the research. He must inform truthfully the patient and his family, the authorities and the industrial when this later provides a drug.
A Clinical Research Nurse (CRN) can contact you and your child to help you throughout the treatment. The nurse is specialized in clinical research and makes sure the trial takes place according to what is required in the protocol.
A Clinical Research Technician (CRT) can contact you and your child. The technician is in charge of collecting your child’s data and to transfer it to the sponsor. A follow-up booklet will help you to write any information which seems important or not. The technician works in the pediatric clinical study unit located in the IHOPE.
Do not hesitate to contact the doctors, CRN, CRT should you need more information.
