Who can enter
- Children and young adults with high-risk solid tumors or central nervous system tumors in whom the disease has recurred (relapse) or has not responded sufficiently to standard treatment (refractory).
- Age: 6 up to and including 21 years.
Goal
In this study, we first established the safe dose of combination therapy for children and young adults. In the second phase, we will evaluate the effect of the combination therapy on the disease in different groups. These groups are divided based on the presence of certain characteristics of the tumor. We will also assess what side effects possibly may be caused by the treatment.
Background
For children and adolescents with cancer in whom the disease has returned after treatment (relapse) or has responded insufficiently (refractory), the treatment options are limited. Therefore, we are looking for new therapies.
In this study, INFORM2 NivEnt, we investigate the combination of the drugs nivolumab and entinostat. A number of drugs are known to have an effect if certain genetic characteristics are present in the tumor. Nivolumab and entinostat could have an effect in the presence of a highly increased number of mutations, an increased level of the protein PD-L1, or multiple copies (so-called amplification) of the MYC(N) gene.
Nivolumab is not chemotherapy but an antibody (immunotherapy). It blocks the protein PD1, thereby removing the brake on the immune system. This allows the body's own immune system to become active against the tumor cells again. Entinostat may have a direct effect on tumors with MYC(N) amplification. There is also evidence suggesting that entinostat may enhance the action of nivolumab.
Nivolumab is approved (registered) in Europe for the treatment of several types of cancer in adults, such as metastatic melanoma or a special type of lung cancer. It has not yet been registered for use in children. Entinostat is a new drug and not yet approved by the authorities. The combination of nivolumab and entinostat has also not yet been approved for the treatment of childhood cancer.
The INFORM2 NivEnt study was set up by ITCC, a partnership that promotes drug research for children with cancer in Europe.