CEB-01 in Paediatrics With Locally Resectable Abdominal Tumours

CEB-01-RLP01-CT trial is first-in-paediatrics, open label, exploratory, externally controlled clinical trial to evaluate safety, efficacy and pharmacokinetics of 7-ethyl-10-hydroxy-camptothecin (SN-38) formulated as a biocompatible polymeric nanofiber membrane (CEB-01) for treatment, in addition to standard of care, of paediatric patients from birth to less than 18 years of age with de novo or recurrent, locally resectable, abdominal tumors in comparison to standard of care.

The trial population will consist of 80 participants who fulfil all the inclusion and exclusion criteria, allocated in three cohorts:

Cohort 1: 20 participants with abdominal STS, open label treatment arm consisting of CEB-01 plus the standard of care (which may include surgery, with or without radiotherapy and/or chemotherapy). The outcomes will be compared to a well-matched population of about 10 participants from the same participating sites, including historical controls or contemporary controls.

Cohort 2: 20 participants with high-risk NB, open label treatment arm consisting of CEB-01 plus the standard of care (which may include surgery, with or without radiotherapy and/or chemotherapy). The outcomes will be compared to a well-matched population of about 10 participants from the same participating sites, including historical controls or contemporary controls.

Cohort 3: 20 participants with rare abdominal tumors including WT, GCT, eMRT, SS, DSRCT and FL-HCC, open label uncontrolled treatment arm to obtain additional safety and efficacy data.

For measurement of primary safety and efficacy endpoints, follow-up will consist of short-term evaluation at 365 ± 30 days and long-term evaluation at 1095 ± 30 days post-surgery as it is considered sufficient for the assessment of the therapeutic effect of CEB-01 regarding local recurrence.

For pharmacokinetic assessment, blood samples will be collected at baseline and at 9 different time points until 56 ± 7 days post-surgery.

For each participant the trial duration will be composed of a screening period for up to 28 days, one day for surgery and 1095 ± 30 days of follow-up.

A Data Safety Monitoring Board (DSMB) will review data in an unblinded fashion; details are given in the DSMB charter. ScheduledThe scheduled review will be performed by the DSMB once 10 randomised and treated participants have completed 6 months of follow-up. The DSMB can be convened at the request of the sponsor should safety signals be detected

Inclusion criteria

To be eligible to participate in this trial, an individual must meet all the following criteria:

• ≤ 18 years.
• Participants must have a diagnosis of:

• De novo or recurrent abdominal soft-tissue sarcoma.
• De novo or recurrent high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification, regardless of response to frontline therapy, diagnosed either by a former histologic verification of neuroblastoma and/or former demonstration of tumour cells in the bone marrow with increased urinary catecholamines at the time of study enrolment. Participants who were initially considered low or intermediate risk but were then reclassified as high risk are also eligible.
• Other tumours: recurrent Wilms tumour, de novo or recurrent Germ cell tumour, de novo or recurrent extracranial malignant rhabdoid tumour, de novo or recurrent synovial sarcoma, de novo or recurrent fibrolamellar hepatocellular carcinoma, and de novo or recurrent desmoplastic small round cell tumour.
• A histology assessment is required for enrolment of de novo cases. A new histology assessment is not required for enrolment of the recurrent cases, but it will be obtained from the resected tumour to assess whether the histology is identical to the original tumour.
• Participants previously treated with irinotecan will be eligible if they have not had documented progressive disease during treatment.
• Participants might have more than one surgically removable lesion.
• Adequate liver, renal, haematological, and cardiac function.
• Participants must have fully recovered from the acute toxic effects (Grade 3 or above) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this trial.
• Landky or Karnosfsky functional performance status score ≥ 50 at screening.
• Female participants of childbearing potential must have a negative urine betahuman chorionic gonadotropin (beta-hCG) pregnancy test at time of screening.
• Female and male participants of childbearing potential must be willing to use adequate contraception throughout the study and for 6 months after surgery.
• Life expectancy greater than 6 months.
• The participant legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained prior to any protocol screening procedures.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this trial:

• Metastatic lesions.
• Other malignancies within past 2 years except for in-situ cancers or basal/squamous cell skin cancer. Subjects with other malignancies are eligible if they are disease-free for at least 24 months or have a clinically stable concurrent malignancy not requiring tumour-directed treatment.
• Active bacterial, viral or fungal infection.
• Known history of active human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C or chronic liver disease. Testing is not required in the absence of clinical findings or suspicion.
• Impossibility of ensuring adequate follow-up.
• Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Contraindication to computed tomography (CT) scan.
• Major surgery within 14 days prior to the implant of study drug or still in recovery after experiencing surgical complications; neither tumour biopsy nor central line insertion are considered a major surgery.
• Other relevant concomitant illnesses.
• Participant' status post-allogeneic stem cell transplant are not eligible.
• Participants with disease of any major organ system that would compromise their ability to withstand therapy.
• Patients with tumour size requiring CEB-01 implant that exceeds the maximum implantable surface area based on Body Surface Area (BSA) correction.
• Patients with known hypersensitivity to SN-38 or any of the CEB-01 excipients.
• Pregnancy or lactation. Pregnant women are excluded from this study; if the patient is a lactating mother, breastfeeding should be discontinued.