Prospective multicenter clinical trial for risk estimation and treatment stratification in low and intermediate risk neuroblastoma patients - NB2015-LR

Phase 3

Not yet recruiting

• Conditions: low and intermediate risk neuroblastoma

• Registration Number: 2024-517295-37-00
• Lead Sponsor: University Of Cologne

Brief Summary

Improvement of event free survival (EFS) of patients with intensified treatment and no impairment of EFS of patients with reduced treatment after treatment allocation by gene expression based risk

stratification.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-25
• Last Update Posted: 2024-10-25

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 280

Inclusion Criteria

Neuroblastoma diagnosed according to the accepted criteria: histological diagnosis from tumor tissue or presence of distinct neuroblastoma cells in the bone marrow and elevated catecholamine metabolites (HVA, VMA) in blood or urine

MYCN not amplified

Stage and age either: a. localized neuroblastoma INRGSS stage L1/L2/INSS stage 1-3 and age at diagnosis ≥18 months and < 21 years b. INSS Stage 4S/INRGSS stage MS c. INSS Stage 4/INRGSS stage M and age at diagnosis <18 months d. INRGSS stage L1/L2 and age at first diagnosis <18 months with relapse or progression of neuroblastoma

Sufficient tumor tissue available from initial diagnosis available for analysis of RNA expression array

Guardians’ informed consent and/ or patient’s informed consent if appropriate according to age and status of psycho-intellectual development

Exclusion Criteria

Participation in other clinical trials

History of earlier VOD/SOS of the liver

Impaired bone marrow function defined by granulocytes <500/μl and/or thrombocytes <50.000/μl unless clearly caused by bone marrow involvement proven by bone marrow cytology or diffuse abnormal osteomedullary signal in the mIBG scintigraphy

HIV infection because of the antiretroviral medication which potentially interferes with the metabolism of the scheduled investigational drugs

Pregnancy or lactation

Insufficient contraception for sexually active study participants as well as female partners of sexually active male trial participants. Patients must be informed about the need of adequate contraception. Moreover, this need for contraception must be understood by the trial participants. Only contraception with a Pearl index <1% are considered as sufficient. For the purpose of this trial, these are long-term parenteral hormones, progesterone releasing implants, intramuscular progesterone, and intrauterine hormone releasing devices, tubal ligation, and vaginal hormonal contraception. This also holds true for adolescents who are at risk to become sexually active during trial participation

Any concomitant non-protocol anticancer therapy

Incomplete initial staging

Known allergy/hypersensitivity to the scheduled drugs

Impaired cardiac function such as insufficiency, heart rate abnormalities and blood pressure abnormalities corresponding to CTCAE 5.0 grade 2 or higher. Hypertension according to age specific reference values clearly due to neuroblastoma is no exclusion criterion

Impaired renal function defined by a reduced glomerular filtration rate <30 ml/min*1,73 m2 determined by serum creatinine (Schwartz formula) or serum cystatin C

Impaired liver function corresponding to CTCAE 5.0 grade 3 or higher unless liver impairment is clearly caused by neuroblastoma in stage 4S/MS patients. Isolated elevation of the transaminases without evidence of impaired liver function is not an exclusion criterion

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Event-free survival (EFS): Time from diagnosis to event or last follow-up for patients without event; event is defined as death for all reasons, progression and relapse following previous complete remission or secondary malignant disease		Event-free survival (EFS): Time from diagnosis to event or last follow-up for patients without event; event is defined as death for all reasons, progression and relapse following previous complete remission or secondary malignant disease

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS): Because of the importance for the individual patient OS has been chosen as secondary endpoint.		Overall Survival (OS): Because of the importance for the individual patient OS has been chosen as secondary endpoint.
Risk factors to impact on EFS and OS: The risk factors age at diagnosis, stage according to INSS and INRG, and copy number alterations of selected genes have been implemented in the INRG classification. These factors will be assessed by multivariate and subgroup analysis. Moreover, the description of patients’ cohorts by these risk factors is mandatory for international comparison of the trial results.		Risk factors to impact on EFS and OS: The risk factors age at diagnosis, stage according to INSS and INRG, and copy number alterations of selected genes have been implemented in the INRG classification. These factors will be assessed by multivariate and subgroup analysis. Moreover, the description of patients’ cohorts by these risk factors is mandatory for international comparison of the trial results.
Response: In neuroblastoma, response to trial treatment is not clearly correlated to outcome. In this trial, response to trial treatment will be compared to historical controls, with a special focus to the cohort with reduced treatment (group C).		Response: In neuroblastoma, response to trial treatment is not clearly correlated to outcome. In this trial, response to trial treatment will be compared to historical controls, with a special focus to the cohort with reduced treatment (group C).
Regression: The percentage of spontaneous regression will be described in patients where the residual primary is observed without cytotoxic treatment and compared to historical controls.		Regression: The percentage of spontaneous regression will be described in patients where the residual primary is observed without cytotoxic treatment and compared to historical controls.
Incidence rates of toxic events: The administered chemotherapy cycles are known to cause treatment related side effects. To estimate the burden for the patients, kind and intensity of side effects will be compared to historical controls and between the patient groups A-C.		Incidence rates of toxic events: The administered chemotherapy cycles are known to cause treatment related side effects. To estimate the burden for the patients, kind and intensity of side effects will be compared to historical controls and between the patient groups A-C.
Additional molecular analysis: The impact of clinical and molecular risk factors such as copy number alterations, telomere maintenance status and mutation status of candidate genes on EFS and OS will be analyzed.		Additional molecular analysis: The impact of clinical and molecular risk factors such as copy number alterations, telomere maintenance status and mutation status of candidate genes on EFS and OS will be analyzed.
Group D, relapsed patients: Outcome of patients with relapse or progression of neuroblastoma diagnosed at the age < 18 months with unfavorable classification.		Group D, relapsed patients: Outcome of patients with relapse or progression of neuroblastoma diagnosed at the age < 18 months with unfavorable classification.

Trial Locations

Locations (29)

Asklepios Klinik Sankt Augustin GmbH; 🇩🇪 Sankt Augustin, Germany

HELIOS Klinikum Erfurt GmbH; 🇩🇪 Erfurt, Germany

Gesundheit Nord gGmbH Klinikverbund Bremen; 🇩🇪 Bremen, Germany

Universitaetsklinikum Aachen AöR; 🇩🇪 Aachen, Germany

Evangelisches Klinikum Bethel gGmbH; 🇩🇪 Bielefeld, Germany

Universitaetsklinikum Giessen und Marburg GmbH; 🇩🇪 Giessen, Germany

Universitaet Leipzig; 🇩🇪 Leipzig, Germany

Universitaetsmedizin Goettingen; 🇩🇪 Goettingen, Germany

Klinikum Dortmund gGmbH; 🇩🇪 Dortmund, Germany

Charite Universitaetsmedizin Berlin KöR; 🇩🇪 Berlin, Germany

Scroll for more (19 remaining)

Asklepios Klinik Sankt Augustin GmbH

🇩🇪Sankt Augustin, Germany

Harald Reinhard

Site contact

+492241249305

h.reinhard@asklepios.com