Clinical Trial FAQ

What is a Clinical Trial?

Clinical trials are research studies that test a new treatment approach. Clinical trials are designed in one of the three categories below.  NANT is focused on doing Phase 1 and 2 trials for relapsed/refractory neuroblastoma.  New treatments that show promising results in NANT Phase 1/2 trials are evaluated for Phase 3 trials, usually performed in a larger clinical trials consortium, such as the Children’s Oncology Group (COG).  NANT investigators participate in COG, and NANT leadership interacts with COG leadership in neuroblastoma to facilitate taking a promising new treatment from a NANT lab to a Phase 3 trial in COG.  

Phase 1 Clinical Trials

Phase 1 clinical trials are the first studies that test new treatments in people after they have shown promise in laboratory research (pre-clinical research).  The main purpose of Phase I studies is to find out what dose and schedule of a new treatment is safe, and to determine the side effects.  These studies usually enroll 3-6 patients at a time at gradually increasing doses. Studies stop entering new patients for a short time while the prior group of patients is evaluated for side effects. In this manner the optimal dose that can be tolerated by patients is defined and can then be tested in a successor trial in larger numbers of patients.  Not all Phase 1 studies go on to more trials. This decision is based on safety, any evidence of anti-tumor activity, and drug availability.

Phase 2 Clinical Trials

Phase 2 trials test the anti-tumor effects of the new treatment using the dose level that was determined in the phase 1 trial. The main purpose of a Phase 2 trial is to find out if certain types of cancer will respond (i.e. tumor sites will get smaller or resolve) to the treatment. Phase 2 trials also provide additional information on the safety of the new treatment.  Some Phase 2 trials are randomized: this means each patient is assigned treatment randomly (like a flip of a coin) to one of 2 or 3 different new treatments to see which one has the best rate of tumor response following treatment..

If Phase 2 trial results show that a significant number of patients have a tumor response, the treatment is well tolerated by patients, and the drug(s) is (are) available, then the new treatment is considered for a Phase 3 trial.

Phase 3 Clinical Trials

Phase 3 trials are large studies, usually enrolling approximately 400 patients over 3-5 years, that test a new treatment compared to the current standard treatment to determine if the new approach improves outcome (measured by the number of patients whose tumors relapse and number of patients who survive).  Patients are randomly (like a flip of the coin) assigned to one of 2 or 3 different treatments (with one choice as the current standard treatment, and the other choices as new treatments).   If a new treatment demonstrates better outcome than the standard treatment, then the new treatment may become standard therapy.  Past Phase 3 trials in neuroblastoma have established high dose chemotherapy with peripheral blood stem cell transplant, isotretinoin, and immunotherapy as standard therapy for newly diagnosed high-risk neuroblastoma. 

Correlative Biology Studies

All phases of clinical trials include “correlative studies”.  This involves taking samples of patients’ blood, bone marrow, and/or tumor for testing in a research lab to learn more about the new treatment, so that future clinical trials can be improved based on this information.  Correlative studies may include measuring drug levels, analyzing tumor genetics, learning more about the mechanism of how the drug works and/or why certain tumors don’t respond, novel methods that can detect minimal amounts of tumor in the blood/bone marrow, and evaluating the patient’s immune function and/or function of normal cells that are known to support tumor growth.  Correlative studies are explained during the informed consent for the specific trial.

How do I know what trials are appropriate for my child?

Every child with relapsed/refractory neuroblastoma is different. Each patient needs to be considered on an individual basis to determine the best possible course of treatment. It is important to discuss treatment options with your primary physician or a physician at a NANT site to choose the optimal therapy based on both medical and personal considerations. Factors such as genetic abnormalities of an individual tumor, prior therapy, organ function, disease sites, tumor MIBG uptake, and availability of peripheral blood stem cells (PBSC) may affect if a child is eligible for a specific NANT study.

It is also important that you choose a study that you feel comfortable with, and that all of your questions are answered. Please contact us for more information.

Why should my child participate in a clinical trial?

When a patient participates in a clinical trial, they receive a treatment that has been developed and extensively reviewed by a team of physicians and laboratory investigators who specialize in the disease being studied.  Clinical trials provide access to new therapies for relapsed/refractory patients that have failed standard therapy. They also contribute to the knowledge about that tumor that helps to design better treatments for the future.  In some cases, clinical trials have also helped to achieve significant advances in survival for children with cancer.

How are NANT clinical trials developed?

The development of a NANT clinical trial begins in a research laboratory, where neuroblastoma tumor cells from patients that have failed standard treatments are used to test the effectiveness of new treatments and how they work. When this laboratory data shows promise for activity against neuroblastoma, the investigator proposes a clinical trial to the NANT Executive Committee, composed of NANT physician leadership. After Executive Committee approval, studies are reviewed by the Scientific Review Committee (SRC) whose members include NANT leadership, pediatric oncologists from NANT sites, collaborating lab investigators, NANT Operations Center leadership, statisticians, parent advisory (NANT-PAC) representatives, NANT external clinical advisors with expertise in neuroblastoma and clinical trial development, and the chair of the COG Neuroblastoma Committee.  After the SRC approves the new clinical trial, a Study Development Committee is formed to finalize the study design, write the study protocol, and complete all the infrastructure needed to perform the trial.  After a study is opened for patient entry, its conduct is overseen by the Study Chair, NANT SRC, and the Operations Center.

Is there a treatment roadmap for relapsed/refractory neuroblastoma?

There is not a definitive treatment roadmap for relapsed/refractory neuroblastoma, since there is not a specific treatment that is successful for all patients. Treatment selection is based on a number of different pieces of information that may include:

1. The timing of the relapse and when it occurred in relation to prior therapy (e.g., during or after the completion of standard therapy).

2. The current tumor location(s) and the pace (aggressiveness) of growth of the relapsed disease.

3. The type of treatment that the patient has received previously.

4. The biologic and genetic characteristics of the tumor. This testing can be done as part of the NANT 04-05 Biology study.

5. Whether or not the tumor has uptake of MIBG on MIBG scans

6. Whether or not the patient has peripheral blood stem cells (PBSC) available to support further therapy.

7. How well the patient’s organs (kidney, heart, liver, lungs) and bone marrow are functioning.

8. The family and patient’s perspectives on quality of life, desires on how to deal with the disease, access to certain hospitals/trials, and medical insurance guidelines.

Selecting a treatment option for relapsed neuroblastoma is very individualized to the patient and is based on the factors above plus many other important considerations which may be unique to specific therapies available. Overall, the treatment pathway for relapsed/refractory neuroblastoma must be individualized and requires discussions between the patient, the patient’s family, and the patient’s primary oncology physician.  NANT sites’ physicians are available to provide medical consultation and to work with the patient’s primary oncology team to enable access to NANT clinical trials.