A phase II trial of 177Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma (LuDO-N Trial)

Chief investigator: Dr Jakob Stenman

Sponsor: Karolinska University Hospital, Stockholm

The prognosis for children with relapsed or refractory high-risk neuroblastoma is dismal with very few survivors. As neuroblastoma is known to be a relatively radiosensitive tumor, targeted intravenous radiotherapy is an attractive treatment option and 131I-mIBG treatment has been used in a relapse setting, since the 1980’s. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, targeted at somatostatin receptors, has recently evolved, as a possibly less myelotoxic alternative to 131I-mIBG treatment, and this treatment has been both effective and well tolerated in the second line treatment of neuroendocrine tumors in adults. Building on the experience from the first pediatric trial on 177Lu-DOTATATE (LuDO Trial, UCLH, London) we aim to perform a multicenter, stage II clinical trial to evaluate the response to single agent 177Lu-DOTATATE treatment in children with relapsed or refractory high-risk neuroblastoma.

In the LuDO-N trial, an intensified dosing schedule will be utilized to administer 177Lu-DOTATATE in two doses, two weeks apart. The aim is to achieve a cumulative whole-body radiation dose of 2,4 Gy over two courses and not exceeding a cumulative renal dose of 23 Gy, in order to avoid renal toxicity. A weight based activity of 200 MBq kg-1 will be used for the first dose and the activity of the second dose will be based on dosimetry. Due to the risk of myelotoxicity, autologous peripheral blood stem cells will be available for all included study subjects, in order to allow for stem cell transplantation, if needed. Response evaluation will be performed at 1 and 4 months after end-of-treatment.

The study will be led and coordinated by the Karolinska University Hospital in Stockholm, Sweden. Patients will initially be recruited from the Nordic countries, Lithuania and from the The Netherlands. Study centers will be established in all participating countries and the 177Lu-DOTATATE (Lutathera®) treatment will be given at the Karolinska University Hospital and at the Prinses Máxima Centrum. The LuDO-N Trial is scheduled to open on May 19, 2021in Sweden, Norway and Denmark, with Finland and Lithuania soon to follow and in The Netherlands later during 2021. The UK has expressed an interest in joining the Trial in 2022. Recruitment is estimated to continue over a period of 3-5 years. Follow-up of patients will continue until 5 years after treatment of the last patient.

For more details about the trials, please see: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-004445-36/NO