ESMART (different tumor types)

Active, not recruiting

Who can enter

Children and teenagers with cancer in whom the disease has returned (relapse) or responded insufficiently to treatment (refractory).
Age: up to 18 years.

Goal

The goal of this study is to assess how safe and effective a drug (or a combination of drugs) is that matches a molecular alteration in the tumor of children with cancer.

Background

Cancer arises by the accumulation of multiple changes in the DNA, also called molecular alterations. These changes can for example result in uncontrolled growth and division of tumor cells, or insufficient sensitivity to chemotherapy. Therefore, more and more drugs are being developed that are specifically aimed at certain molecular alterations in the tumor.

Previously, the iTHER-study determined which alterations are present in the tumor (the so-called ‘molecular profile’) of children with relapsed or refractory disease. When such an alteration is present, treatment with a drug directly targeting this alteration may be possible in certain cases. This is also called ‘precision medicine’ or ‘targeted therapy’. These treatments are part of the clinical study ESMART.

The ESMART study is divided into different treatment options (so-called ‘arms’). In doing so, we try to choose a drug that matches the molecular alteration in the tumor.

The following ‘arms’ have started (at the moment, all arms are closed for inclusion):

Study arms

Ribociclib is a drug that inhibits so-called CDK enzymes. These enzymes enable tumor cells to proliferate. Ribociclib is already used for the treatment of women with breast cancer, but has not yet been registered for the treatment of children. TOTEM has already been used in children, especially in neuroblastoma. By adding ribociclib to the treatment with TOTEM we hope that the treatment will be more effective.
Irinotecan is a chemotherapeutic drug that causes DNA-strand brakes. Olaparib blocks the so-called PARP enzyme, involved in DNA repair, thus preventing damaged cancer cells from repairing themselves. This way, the cancer cells die. Adding olaparib to the treatment with irinotecan may enhance its efficacy. In a recent study among adults with colon cancer, combination of olaparib with irinotecan resulted in stable disease in a number of patients.
The drugs lirilumab and nivolumab are both antibodies, each targeting a different so-called ‘immune checkpoint’. Tumor cells use these immune checkpoints to put a brake on the immune system. Lirilumab and nivolumab release this brake, and enhance the activity of the immune system against tumor cells. Combining lirilumab with nivolumab may be more effective. Nivolumab has been used in children before, but in a different setting. Lirilumab has not yet been used in children, but has been used in adults, also in combination with nivolumab.

This study was initiated by ITCC, an international collaboration that promotes drug research for children with cancer in Europe.

This study is momentarily closed for inclusion.

Last reviewed

September 16, 2025

Study details
Official title
‘European proof-of-concept therapeutic stratification trial of molecular anomalies in relapsed or refractory tumors.’
Cancer type
- Hematologic malignancies
- Solid tumors
Phase
1/2, multi arm
Maximum number of patients
280, of whom 25 are expected to participate in the Netherlands
Start date
April 5, 2018
Status
Closed for inclusion
Local principal investigator
Dr. N. van Eijkelenburg
Sponsor
Institut Gustave Roussy, Villejuif, France
Approval
The study of this new treatment has been reviewed by an accredited medical research ethics committee. This committee has decided that it is justified to ask patients to participate in this study. More information can be found at: CCMO.
Trial registry number
EudraCT number 2016-000133-40

The above information is intended as a brief summary only and may not reflect the most up-to-date information. For full details and the current status of a protocol, physicians can contact the Princess Máxima Center directly.

ESMART (different tumor types)

Who can enter

Goal

Background

Study arms

Arm A: Ribociclib in combination with topotecan and temozolomide (TOTEM)

Arm C: AZD1775 in combination with carboplatin

Arm D: Olaparib in combination with irinotecan

Arm I: Enasidenib

Arm J: Lirilumab in combination with nivolumab

Last reviewed

Study details

Study details