CEB-01 in Paediatrics With Locally Resectable Abdominal Tumours.
- Conditions
- Locally Resectable Paediatrics Tumours
- Interventions
- Procedure: Standard surgery
- Registration Number
- NCT06986811
- Lead Sponsor
- CEBIOTEX
- Brief Summary
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 a localy resectable abdominal tumours including neuroblastoma soft-tissue sarcoma, Wilms, germ cell tumours and other tumours, in comparison to standard of care.
Study treatment CEB-01: It is an investigational medicinal product consisting of a novel formulation for local release of chemotherapy. It is composed of a biocompatible and biodegradable nanofiber membrane poly(lactic-co-glycolic acid) (PLGA) which is loaded with the drug SN-38 (the main metabolite of irinotecan). The membrane is inert, non-toxic, and has shown efficacy in cell lines and xenograft models. In the preclinical setting, CEB-01 prevents relapse of surgically excised tumours and is based on a unique technology of biodegradable nanofibers, which can deliver anti-tumour SN-38 directly into the resected tumour bed. This targeted delivery thus eliminates remnant cancer cells after surgical procedures and effectively controls residual microscopic disease.
The potential benefit of a local treatment with CEB-01 to avoid local recurrence is highly supported by several animal models and a clinical trial in adults with de novo or recurrent STS, although the clinical experience, gathered so far, is limited.
- Detailed Description
1. Primary and Secondary Objectives and Endpoints Objective primary (1) To assess the efficacy of CEB01 in locally resectable abdominal neuroblastoma, soft tissue sarcoma, Wilms, germ cell tumours and other tumours in paediatrics.
Endpoint: Adverse Events (AE), serious and non-serious, with theirfrequency, severity, and relatedness to study drug and coded according to the most updated version of the Common Terminology Criteria for Adverse Events (CTCAE).
Objectives secondary (2) To assess the efficacy of CEB-01 in locally resectable abdominal neuroblastoma, soft- tissue sarcoma, Wilms, germ cell tumours and otherntumours in paediatrics.
Endpoints:
* Progression-free survival (PFS).
* Overall survival (OS).
* Local recurrence-free survival (LRFS).
* New lesions either distant or metastatic by RECIST 1.1.
* Quality of Life Questionnaire (QoL) (3) To characterise the pharmacokinetics of SN-38.
Endpoints:
* Area under the concentration-time curve (AUC0-inf) of SN-38.
* Maximum concentration (Cmax) of SN-38.
* Time of maximum plasma concentration (Tmax) of SN-38.
* Terminal half-life (t1/2) of SN-38.
2. Overall Design.
Design: Three cohorts of 20 participants each, plus 20 subjects from well- matched external populations. Intervention Model: Parallel group. Control: External control arm treated with standard of care (SOC). Trial Intervention Assignment Method: Open label, with external well-matched control arm.
Population Type: Paediatrics.Population Diagnosis or Condition: Male and female patients aged from birth to less than 18 years with a locally resectable tumours including soft-tissue sarcoma (STS), neuroblastoma (NB), and other tumours such as Wilms tumour (WT), germ cell tumours (GCT), extracranial malignant rhabdoid tumour (eMRT), synovial sarcoma (SS), desmoplastic small round cell tumour (DSRCT) and fibrolamellar hepatocellular carcinoma (FL-HCC).
Population Age: From birth to less than 18 years old at screening. Site Distribution: Single site: Paediatric Cancer Center Barcelona (PCCB) at Hospital Sant Joan de Déu, Barcelona, Spain.
Number of Cohorts: There will be 3 cohorts described as follows:
* Cohort 1: Abdominal STS, in 20 participants, open label treatment arm CEB-01 plus SOC (consisting of surgery with/without radiotherapy and/or chemotherapy) compared with a well-matched population of approximately 10 patients, from the same participating sites, including historical controls (e.g. within the last 10 years) or contemporary controls (e.g. subjects that fulfil inclusion and exclusion criteria, but do not desire to receive experimental treatment) treated with SOC (consisting of surgery with/without radiotherapy and/or chemotherapy) will be the external control arm.
. Cohort 2: High-risk NB, in 20 participants, open label treatment arm CEB-01 plus SOC (consisting of surgery with/without radiotherapy and/or chemotherapy) compared with a well-matched population of approximately 10 patients, from the same participating sites, including historical controls (e.g. within the last 10 years) or contemporary controls (e.g. subjects that fulfil inclusion and exclusion criteria, but do not desire to receive experimental treatment) treated with SOC (consisting of surgery with/without radiotherapy and/or chemotherapy) will be the external control arm.
* Cohort 3: Abdominal tumours including WT, GCT, eMRT, SS, DSRCT and FL-HCC in 20 participants. Open-label uncontrolled treatment arm to obtain additional safety and efficacy data.
Blinding: This is an open label clinical trial. Number of Participants: 60 participants split in 3 cohorts plus 20 from 2 well matched-external cohorts of ten participants each.
Arms and Duration: For each participant, there will be an enrolment period of up to 28 days for screening and a follow-up of 3 years. Day 1 will be the day of surgery with or without implant of the membrane, and measurement of the primary endpoint on Day 3 ± 30 days from the day of surgery. The total enrolment period will be approximately 12 months, therefore from First Participant First Visit (FPFV) expected to be in Q1 2025 to Last Participant Last Visit (LPLV) expected to be in Q1 2029.
Committees: A Data Safety Monitoring Board (DSMB) will review data in an unblinded fashion; details are given in the DSMB charter. 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.
3. Trial Schema Cohort 1 Screening: Up to 28 days before surgery. Population: paediatrics with locally resectable abdominal soft-tissue sarcoma.
Treatment: On Day 1, CEB-01 single implantation of one or multiple membranes adjusted to individual patient needs based on area of the surgical bed plus a small 1 cm margin immediately following tumour resection surgery. The minimum paediatric membrane size implanted to be 15 cm2 corresponding to a SN-38 dose of 0.75 mg.
Primary endpoint: Safety and efficacy up to Day 1095 ± 30 days.
Cohort 2 Screening: Up to 28 days before surgery. Population: paediatrics with locally resectable abdominal neuroblastoma.
Treatment: On Day 1, CEB-01 single implantation of one or multiple membranes adjusted to individual patient needs based on area of the surgical bed plus a small 1 cm margin immediately following tumour resection surgery. The minimum paediatric membrane size implanted to be 15 cm2 corresponding to a SN-38 dose of 0.75 mg.
Primary endpoint: Safety and efficacy up to Day 1095 ± 30 days.
Cohort 3 Screening: Up to 28 days before surgery. Population: Population: paediatrics with locally resectable abdominal tumours including Wilms tumour, Germ cell tumour, extracranial malignant, rhabdoid tumour, synovial sarcoma, desmoplastic small, round cell tumour and fibrolamellar hepatocellular carcinoma.
Treatment: On Day 1, CEB-01 single implantation of one or multiple membranes adjusted to individual patient needs based on area of the surgical bed plus a small 1 cm margin immediately following tumour resection surgery. The minimum paediatric membrane size implanted to be 15 cm2 corresponding to a SN-38 dose of 0.75 mg.
Primary endpoint: Safety and efficacy up to Day 1095 ± 30 days.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
To be eligible to participate in this trial, an individual must meet all the following criteria:
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≤ 18 years.
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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.
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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.
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Participants previously treated with irinotecan will be eligible if they have not had documented progressive disease during treatment.
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Participants might have more than one surgically removable lesion.
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Adequate liver, renal, haematological, and cardiac function.
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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.
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Landky or Karnosfsky functional performance status score ≥ 50 at screening.
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Female participants of childbearing potential must have a negative urine betahuman chorionic gonadotropin (beta-hCG) pregnancy test at time of screening.
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Female and male participants of childbearing potential must be willing to use adequate contraception throughout the study and for 6 months after surgery.
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Life expectancy greater than 6 months.
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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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard surgery and CEB-01 implant after surgery Standard surgery Procedure/Surgery: Standard surgery The location and size of the tumor determine the type of surgery. Drug: CEB-01 It is novel formulation for local release of chemotherapy. It consists of a biocompatible and biodegradable nanofiber membrane made of poly(lactic-co-glycolic acid) (PLGA), which is loaded with the anti-tumor drug SN-38 and implanted in the surgical bed after tumor removal. Standard surgery and CEB-01 implant after surgery CEB-01 Procedure/Surgery: Standard surgery The location and size of the tumor determine the type of surgery. Drug: CEB-01 It is novel formulation for local release of chemotherapy. It consists of a biocompatible and biodegradable nanofiber membrane made of poly(lactic-co-glycolic acid) (PLGA), which is loaded with the anti-tumor drug SN-38 and implanted in the surgical bed after tumor removal. Active Comparator: Arm 2 standard surgery Standard surgery Procedure/Surgery: Standard surgery The location and size of the tumor determine the type of surgery.
- Primary Outcome Measures
Name Time Method Frequency of Adverse Events (AEs) (Safety) Through study completion, average 3 years Adverse Events (AE), serious and non-serious, with their frequency, severity, and relatedness to study drug and coded according to the most updated version of the Common Terminology Criteria for Adverse Events (CTCAE).
- Secondary Outcome Measures
Name Time Method Time of maximum plasma concentration (Tmax) of SN38. During 60 days Time from the surgery to the moment with the highest concentration of SN-38 in the peripheral blood samples taken at sequential timepoints
Terminal half-life (t1/2) of SN-38 During 60 days he time required for the plasma concentration of SN-38 to fall by 50% from the Cmax
Progression-free survival (PFS) Rhrough study completion, average 3 years Defined as the time from surgery to objective tumour progression or death from any cause.
Overall survival (OS). Through study completion, average 3 years Defined as time from surgery to death from any cause.
Local recurrence-free survival (LRFS) Through study completion, average 3 years Defined as the time from surgery until the progression of the disease in the area of implanted CEB-01.
New lesions either distant or metastatic by RECIST 1.1. Through study completion, average 3 years Number of new lesions either distant or metastatic by RECIST 1.1.
Area under the concentration-time curve (AUC0-inf) of SN-38 During 60 days Represents the total SN-38 exposure in the peripheral blood across time
Maximum concentration (Cmax) of SN-38. During 60 days The highest concentration of SN-38 in the peripheral blood samples taken at sequential timepoints
Trial Locations
- Locations (1)
Hospital Sant Joan de Déu
🇪🇸Esplugues de Llobregat, Barcelona, Spain