Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03165292
Recruitment Status : Recruiting
First Posted : May 24, 2017
Last Update Posted : June 3, 2021
Sponsor:
Collaborator:
National Cancer Institute, France
Information provided by (Responsible Party):
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 positive conclusion, the relative efficacy of both arms will then be evaluated comparatively.

Condition or disease Intervention/treatment Phase
Very High Risk Neuroblastoma Radiation: 131I-mIBG Drug: Topotecan Drug: Thiotepa Procedure: Autologous stem cell transplant Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: Arm A: High administered activity 131I-mIBG radiolabelled with iodine-131 and 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.
Radiation: 131I-mIBG
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

Drug: Topotecan
Day 1-5 Topotecan 0.7 mg/m^2 daily Day 15-19 Topotecan 0.7 mg/m^2 daily

Procedure: Autologous stem cell transplant
ASCT as soon as radiation level allows it in ARM A

Experimental: Arm B: High dose 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.
Drug: Thiotepa
Day 1-3 Thiotepa 300 mg/m^2/day

Procedure: Autologous stem cell transplant
ASCT as soon as radiation level allows it in ARM A




Primary Outcome Measures :
  1. Event Free Survival (EFS) [ Time Frame: From the randomisation into the VERITAS trial to 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03165292


Contacts
Layout table for location contacts
Contact: Dominique VALTEAU COUANET, MD, PhD 0142114211 ext +33 dominique.valteau-couanet@gustaveroussy.fr
Contact: Habiba ATTALAH, PhD 0142114211 ext +33 Habiba.ATTALAH@gustaveroussy.fr

Locations
Layout table for location information
France
Gustave Roussy Recruiting
Villejuif, Val De Marne, France, 94805
Contact: Habiba ATTALAH, PhD    0142115886 ext +33    habiba.attalah@gustaveroussy.fr   
Principal Investigator: Dominique VALTEAU COUANET, MD, PhD         
Netherlands
Princess Maxima Center Recruiting
Utrecht, Netherlands
Contact: Kathelijne Dr. Kathelijne Kraal, MD       K.C.J.Kraal@prinsesmaximacentrum.nl   
Contact: Jaap Mur, PhD       J. <J.Mur@prinsesmaximacentrum.nl>   
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
National Cancer Institute, France
Investigators
Layout table for investigator information
Principal Investigator: Dominique Valteau-Couanet, MD, PhD Gustave roussy Paris, France
Layout table for additonal information
Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT03165292    
Other Study ID Numbers: 2015-003130-27
2015/2294 ( Other Identifier: CSET number )
First Posted: May 24, 2017    Key Record Dates
Last Update Posted: June 3, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Clinical Study Report (CSR)

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Topotecan
Thiotepa
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs