Evaluation of 2 Intensification Treatment Strategies for Neuroblastoma Patients With a Poor Response to Induction

• Status: Recruiting
• Trial end date: 2026-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The main objective is to evaluate the efficacy of two intensified consolidation strategies in very-high risk neuroblastoma (VHR-NBL) patients in terms of event-free survival from randomisation date. This evaluation will follow a hierarchical testing procedure: each experimental treatment will be first evaluated as a single-arm phase 2 study, and in case of positive conclusion, the relative efficacy of both arms will then be evaluated comparatively.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Collaborators: French National Cancer Institute; National Cancer Institute, France; SIOPEN
• Treatments: Thiotepa; Topotecan

Criteria

Inclusion Criteria:

1. Metastatic neuroblastoma (NBL)

2. Patient previously treated within the ongoing High Risk Neuroblastoma SIOPEN study or treated with the current standard treatment for very high risk neuroblastoma off-trial

3. mIBG scintigraphy positive at diagnosis and after induction chemotherapy (pre BuMel evaluation).

4. Metastatic response after induction chemotherapy lower than the ongoing High Risk Neuroblastoma SIOPEN trial criteria to be eligible for High Dose Chemotherapy (metastatic response worse than partial response (< PR) or SIOPEN score > 3)

5. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use acceptable and appropriate contraception while on study drug and for one year after stopping the study drug. Acceptable contraception are defined in CTFG Guidelines "Recommendations related to contraception and pregnancy testing in clinical trials". Female patients who are lactating must agree to stop breast-feeding.

6. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local regional or national guidelines.

7. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.

Exclusion Criteria:

1. Parenchymal brain metastasis (even one)

2. Progressive disease at study entry

3. Previous high-dose therapy and Autologous Stem Cell Reinfusion

4. Performance status (Karnofsky, Lansky) <70%

5. Patient having received other therapy for cancer treatment than those allowed as per the ongoing High Risk Neuroblastoma SIOPEN trial or as defined in the future frontlines protocol (for HRNBL1 trial : after induction + 2 TVD)

6. Impaired organ function (liver, kidney, heart, lungs)

• Shortening fraction <28%, or ejection fraction <55%, or clinical evidence of congestive heart failure or uncontrolled cardiac rhythm disturbance

• Dyspnea at rest and/or pulse oxymetry <95% in air

• ALT, Bilirubin > 2 ULN

• Creatinine clearance and/or GFR < 60 ml/min/1.73m^2 and serum creatinine >/= 1.5 mg/dl

7. Any uncontrolled intercurrent illness or infection that in the investigator's opinion would impair study participation

8. Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines

9. Patient allergic to peanut or soya

10. Chronic inflammatory bowel disease and/or bowel obstruction

11. Pregnant or breastfeeding women

12. Known hypersensitivity to the active substance or to any of the excipients of study drugs

13. Known hypersensitivity to dacarbazine

14. Concomitant use with St John's Wort