Very High Risk NeuroblastomaPhase 2VERITASNCT03165292
Evaluation of 2 Intensification Treatment Strategies for Neuroblastoma Patients With a Poor Response to Induction
A Phase 2 study testing mIBG, Topotecan and Thiotepa in people with Very High Risk Neuroblastoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 9 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Very High Risk Neuroblastoma
- What is being tested?
- mIBG, Topotecan and Thiotepa
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 9 sitesin 5 countries
- Study dates
- 1 Oct 2018to 28 Mar 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Metastatic neuroblastoma (NBL)
- 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
- mIBG scintigraphy positive at diagnosis and after induction chemotherapy (pre BuMel evaluation).
- 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)
- 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.
- 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.
- Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
Who cannot join
- Parenchymal brain metastasis (even one)
- Progressive disease at study entry
- Previous high-dose therapy and Autologous Stem Cell Reinfusion
- Performance status (Karnofsky, Lansky) <70%
- 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)
- Impaired organ function (liver, kidney, heart, lungs)
Show all 18Show fewer
- 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
- Any uncontrolled intercurrent illness or infection that in the investigator's opinion would impair study participation
- Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines
- Patient allergic to peanut or soya
- Chronic inflammatory bowel disease and/or bowel obstruction
- Pregnant or breastfeeding women
- Known hypersensitivity to the active substance or to any of the excipients of study drugs
- Known hypersensitivity to dacarbazine
- Concomitant use with St John's Wort
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
Italy3 sites
Meyer children's Hospita
Florence, 50139
Fondazione IRCCS Istituto nazionaleTumori
Milan, 20133
Ospedale Pediatrico Bambino Gesù
Roma
Austria2 sites
Medizinische Universität Innsbruck
Innsbruck, 356020
St. Anna Kinderspital GmbH
Vienna, 1090
Spain2 sites
Hospital Universitario Cruces
Cruces, 48903
Hospital Universitario y policnico La Fe
Valencia, 46026
About this study
Official title: An International Multicenter Phase II Randomised Trial Evaluating and Comparing Two Intensification Treatment Strategies for Metastatic Neuroblastoma Patients With a Poor Response to Induction Chemotherapy
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.
Read the 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.
For this reason, this trial does not compare two single treatments, but compares two sequential treatment strategies. In these two strategies, most of the components are evidence-based best practice, although the level of evidence supporting each component varies. There is one experimental component in each strategy. Indeed, none of these two treatment schedules can be considered as standard therapy, and none has been previously compared with any standard therapy in a randomised trial.
Although it might be considered that this trial should have a standard therapy arm as a comparator, analysis of patients treated in the SIOPEN HR NBL trial 1 who have failed to meet the R1 criteria has shown a wide heterogeneity of treatments. Therefore, there is no recognised or accepted standard treatment in this very high-risk patient group, and no guidelines exist for poor responders. Survival in this very high-risk group is currently very poor. Considering all these points, it is considered ethical to compare two experimental schedules without a standard comparator.
This trial compares two such strategies in a randomised way. Patients are eligible for entry into the trial if they fail to have an adequate response to induction and therefore cannot proceed directly within the high-risk study to BuMel PBSCR. Eligible patients will be randomised at that time point, even though further standard treatment will be administered before the randomised element, and there may be circumstances when an individual patient although randomised to a particular strategy, is unable to receive the randomised element of treatment. For example, if it proves impossible to perform an adequate PBSC harvest. All randomised patients will be analysed on an intention to treat basis.
Following randomisation, all patients will continue with standard dose chemotherapy with irinotecan and temozolomide for three courses to allow for PBSC harvest (it is not mandatory to have clear bone marrows before attempting a harvest) and to facilitate scheduling of the randomised element of the study which may necessitate referral to another centre.
The patients will then receive one of two investigational intensification therapies according to random allocation:
- high administered activity 131I-mIBG and topotecan and ASCR.
- high-dose thiotepa and ASCR Then all patients will proceed to second high-dose chemotherapy: BuMel and ASCR.
The intensified consolidation chemotherapy will be followed by external radiotherapy as appropriate, by local surgery of the tumour residues as appropriate.
- Conditions
- Very High Risk Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mIBGRadiation
Day 1 131I-mIBG course 1: about 444MBq/kg with in vivo whole-body dosimetry Day 15 131I-mIBG course 2: the target is to deliver a combined whole-body radiation dose of 4 Gy
TopotecanDrug
Day 1-5 Topotecan 0.7 mg/m2 daily Day 15-19 Topotecan 0.7 mg/m2 daily
ThiotepaDrug
Day 1-3 Thiotepa
Autologous stem cell transplantProcedure or surgery
ASCT as soon as radiation level allows it in ARM A
| Study group | Role | What they receive |
|---|---|---|
| Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan | Experimental | 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. Receives: Radiation: mIBG; Drug: Topotecan; Procedure: Autologous stem cell transplant |
| Arm B: High dose Thiotepa | Experimental | 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. Receives: Drug: Thiotepa; Procedure: Autologous stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival (EFS)
Measured: From the randomisation into the VERITAS trial to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2017
- Study start1 Oct 2018
- Primary completion28 Aug 2023
- Study completion28 Mar 2024
Why it stopped: The Sponsor has been notified of an interruption in the international supply, and there is a possibility that 131I-mlBG would be unavailable to patients randomised to arm A of the trial
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Very High Risk NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France
- Responsible party
- Sponsor
- Investigators
- Dominique Valteau-Couanet, MD, PhD, Principal investigator, Gustave roussy Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03165292
- Sponsor's protocol ID
- 2015-003130-27
- Other IDs
- 2015/2294, 2015
- Acronym
- VERITAS
- Status last verified
- Aug 2025
- First submitted
- 23 May 2017
- Last updated
- 2 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International Multicenter Phase II Randomised Trial Evaluating and Comparing Two Intensification Treatment Strategies for Metastatic Neuroblastoma Patients With a Poor Response to Induction Chemotherapy
- ClinicalTrials.gov ID
- NCT03165292
- Acronym / sponsor ID
- VERITAS / 2015-003130-27
- Conditions
- Very High Risk Neuroblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor has been notified of an interruption in the international supply, and there is a possibility that 131I-mlBG would be unavailable to patients randomised to arm A of the trial
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Collaborators
- National Cancer Institute, France
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 28 Aug 2023 (actual)
- Study completion
- 28 Mar 2024 (actual)
- First posted
- 24 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
For this reason, this trial does not compare two single treatments, but compares two sequential treatment strategies. In these two strategies, most of the components are evidence-based best practice, although the level of evidence supporting each component varies. There is one experimental component in each strategy. Indeed, none of these two treatment schedules can be considered as standard therapy, and none has been previously compared with any standard therapy in a randomised trial.
Although it might be considered that this trial should have a standard therapy arm as a comparator, analysis of patients treated in the SIOPEN HR NBL trial 1 who have failed to meet the R1 criteria has shown a wide heterogeneity of treatments. Therefore, there is no recognised or accepted standard treatment in this very high-risk patient group, and no guidelines exist for poor responders. Survival in this very high-risk group is currently very poor. Considering all these points, it is considered ethical to compare two experimental schedules without a standard comparator.
This trial compares two such strategies in a randomised way. Patients are eligible for entry into the trial if they fail to have an adequate response to induction and therefore cannot proceed directly within the high-risk study to BuMel PBSCR. Eligible patients will be randomised at that time point, even though further standard treatment will be administered before the randomised element, and there may be circumstances when an individual patient although randomised to a particular strategy, is unable to receive the randomised element of treatment. For example, if it proves impossible to perform an adequate PBSC harvest. All randomised patients will be analysed on an intention to treat basis.
Following randomisation, all patients will continue with standard dose chemotherapy with irinotecan and temozolomide for three courses to allow for PBSC harvest (it is not mandatory to have clear bone marrows before attempting a harvest) and to facilitate scheduling of the randomised element of the study which may necessitate referral to another centre.
The patients will then receive one of two investigational intensification therapies according to random allocation:
- high administered activity 131I-mIBG and topotecan and ASCR.
- high-dose thiotepa and ASCR Then all patients will proceed to second high-dose chemotherapy: BuMel and ASCR.
The intensified consolidation chemotherapy will be followed by external radiotherapy as appropriate, by local surgery of the tumour residues as appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan | Experimental | Radiation: mIBG, Drug: Topotecan, Procedure: Autologous stem cell transplantThe 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 | Experimental | Drug: Thiotepa, Procedure: Autologous stem cell transplantThe 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Metastatic neuroblastoma (NBL)
- 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
- mIBG scintigraphy positive at diagnosis and after induction chemotherapy (pre BuMel evaluation).
- 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)
- 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.
Key exclusion criteria (18 listed)
- Parenchymal brain metastasis (even one)
- Progressive disease at study entry
- Previous high-dose therapy and Autologous Stem Cell Reinfusion
- Performance status (Karnofsky, Lansky) <70%
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mIBGDay 1 131I-mIBG course 1: about 444MBq/kg with in vivo whole-body dosimetry Day 15 131I-mIBG course 2: the target is to deliver a combined whole-body radiation dose of 4 Gy | Radiation | Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan |
| TopotecanDay 1-5 Topotecan 0.7 mg/m2 daily Day 15-19 Topotecan 0.7 mg/m2 daily | Drug | Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan |
| ThiotepaDay 1-3 Thiotepa | Drug | Arm B: High dose Thiotepa |
| Autologous stem cell transplantASCT as soon as radiation level allows it in ARM A | Procedure or surgery | Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and Topotecan, Arm B: High dose Thiotepa |
Primary outcome
Event Free Survival (EFS)
Time frame: From the randomisation into the VERITAS trial to 3 years
Results and safety
The study was stopped early (reason given: The Sponsor has been notified of an interruption in the international supply, and there is a possibility that 131I-mlBG would be unavailable to patients randomised to arm A of the trial). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- Individual participant dataSharing planned: Yes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique Valteau-Couanet, MD, PhD principal investigator
Gustave roussy Paris, France
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing mIBG, Topotecan and Thiotepa in people with Very High Risk Neuroblastoma, run by Gustave Roussy, Cancer Campus, Grand Paris at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy, Austria, Spain, France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The Sponsor has been notified of an interruption in the international supply, and there is a possibility that 131I-mlBG would be unavailable to patients randomised to arm A of the trial). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event Free Survival (EFS) (time frame: From the randomisation into the VERITAS trial to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025.