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

Phase 2

Terminated

• Conditions: Very High Risk Neuroblastoma
• Interventions: Radiation: mIBG; Drug: Thiotepa; Drug: Topotecan; Procedure: Autologous stem cell transplant

• Registration Number: NCT03165292
• Lead Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Brief 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 p...

Detailed Description

High-risk metastatic neuroblastoma is not cured by a single treatment. All patients who have become long-term survivors have received sequential treatments with various drugs.
...

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2017-05-23
• Study First Submitted QC: 2017-05-23
• Study First Posted: 2017-05-24
• Study Start: 2018-10-01
• Primary Completion: 2023-08-28
• Study Completion: 2024-03-28
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-14
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

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.

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan	mIBG	The trial will evaluate two randomised arms. Each arm includes * three cycles of Temozolomide-Irinotecan, similar in both arms, * a specific consolidation course detailed hereinafter, * a BuMel sequence, followed by an ASCT, similar in both arms, * external radiotherapy as appropriate, and/or local surgery of the tumour residues as appropriate.
Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan	Autologous stem cell transplant	The trial will evaluate two randomised arms. Each arm includes * three cycles of Temozolomide-Irinotecan, similar in both arms, * a specific consolidation course detailed hereinafter, * a BuMel sequence, followed by an ASCT, similar in both arms, * external radiotherapy as appropriate, and/or local surgery of the tumour residues as appropriate.
Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan	Topotecan	The trial will evaluate two randomised arms. Each arm includes * three cycles of Temozolomide-Irinotecan, similar in both arms, * a specific consolidation course detailed hereinafter, * a BuMel sequence, followed by an ASCT, similar in both arms, * external radiotherapy as appropriate, and/or local surgery of the tumour residues as appropriate.
Arm B: High dose Thiotepa	Autologous stem cell transplant	The trial will evaluate two randomised arms. Each arm includes * three cycles of Temozolomide-Irinotecan, similar in both arms, * a specific consolidation course detailed hereinafter, * a BuMel sequence, followed by an ASCT, similar in both arms, * external radiotherapy as appropriate, and/or local surgery of the tumour residues as appropriate.
Arm B: High dose Thiotepa	Thiotepa	The trial will evaluate two randomised arms. Each arm includes * three cycles of Temozolomide-Irinotecan, similar in both arms, * a specific consolidation course detailed hereinafter, * a BuMel sequence, followed by an ASCT, similar in both arms, * external radiotherapy as appropriate, and/or local surgery of the tumour residues as appropriate.

Primary Outcome Measures

Name	Time	Method
Event Free Survival (EFS)	From the randomisation into the VERITAS trial to 3 years

Trial Locations

Locations (9)

Gustave Roussy; 🇫🇷 Villejuif, Val De Marne, France

St. Anna Kinderspital GmbH; 🇦🇹 Vienna, Austria

Fondazione IRCCS Istituto nazionaleTumori; 🇮🇹 Milano, Italy

Meyer children's Hospita; 🇮🇹 Florence, Italy

Princess Maxima Center; 🇳🇱 Utrecht, Netherlands

Ospedale Pediatrico Bambino Gesù; 🇮🇹 Roma, Italy

Hospital Universitario y policnico La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario Cruces; 🇪🇸 Cruces, Spain

Medizinische Universität Innsbruck; 🇦🇹 Innsbruck, Austria