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New treatment option for High-Risk Neuroblastoma
Official title High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)
ClinicalTrials.gov ID: NCT04221035
What this study is testing
What is Vincristine?
Vincristine is an investigational medicine, being studied as a potential treatment for high-risk neuroblastoma.
Also referred to as L01CA02.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is an international multicenter, open-label, randomized phase III trial including three sequential randomizations to assess efficacy of induction and consolidation chemotherapies and radiotherapy for patients with high-risk neuroblastoma.
- Phase 3: a large, late-stage study
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages up to 21
You may be able to join if
- Enrollment in HR-NBL2 will be performed:
- at diagnosis before the beginning of chemotherapy or
- up to 21 days after one course of Carboplatin-Etoposide for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN...
- up to 21 days after one course of the current protocol for R-I randomisation (RAPID COJEC/GPOH) low/intermediate risk neuroblastoma in...
- Established diagnosis of neuroblastoma according to the SIOPEN- modified International Neuroblastoma Risk Group (INRG) criteria, High-risk...
You likely can't join if
- at diagnosis, patients can still be enrolled in HR- NBL2 trial with parents'/patient's consent before or within 3 weeks from the beginning of...
- \- Stage M neuroblastoma above 365 days of age at diagnosis, any MYCN status, EXCEPT patients with stage M or Ms 12-18 months old with numerical...
- Age \< 21 years at the time of randomization
- Complete response (CR) or partial response (PR) at metastatic sites:
- Bone disease: mIBG uptake completely resolved or SIOPEN score ≤ 3 and at least 50% reduction in mIBG score (or ≤ 3 bone lesions and at least 50%...
- Bone marrow disease: CR and/or minimal disease (MD) according to International Neuroblastoma Response Criteria
See the full eligibility criteria
Who can join
- Enrollment in HR-NBL2 will be performed:
- at diagnosis before the beginning of chemotherapy or
- up to 21 days after one course of Carboplatin-Etoposide for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification or patients with metastatic neuroblastoma treated in...
- up to 21 days after one course of the current protocol for R-I randomisation (RAPID COJEC/GPOH) low/intermediate risk neuroblastoma in Germany/Netherlands for patients with localized neuroblastoma or infants with...
- Established diagnosis of neuroblastoma according to the SIOPEN- modified International Neuroblastoma Risk Group (INRG) criteria, High-risk neuroblastoma defined as:
- Stage M neuroblastoma above 365 days of age at diagnosis (no upper age limit) and Ms neuroblastoma 12-18 months old, any MYCN status or
- L2, M or Ms neuroblastoma any age with MYCN amplification, or focal high level MYC or MYCL amplification. In Germany, patients aged less than 18 months with stage M and without MYCN amplification will not be enrolled in...
- No previous chemotherapy or up to 21 days after one cycle of Carboplatin-Etoposide chemotherapy for patients with localized neuroblastoma or infants with metastatic neuroblastoma with MYCN amplification or patients with...
- Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use acceptable and appropriate contraception...
- Written informed consent to enter the HR-NBL2 protocol from patient or parents/legal representative, patient, and age-appropriate assent.
- Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
- Patients should be able and willing to comply with study visits and procedures as per protocol R-I eligibility criteria: \- Written informed consent to enter the R-I randomisation from patient or parents/legal...
What rules you out
- at diagnosis, patients can still be enrolled in HR- NBL2 trial with parents'/patient's consent before or within 3 weeks from the beginning of chemotherapy R-HDC randomisation (Single HDC Bu-Mel/ Tandem HDC...
- \- Stage M neuroblastoma above 365 days of age at diagnosis, any MYCN status, EXCEPT patients with stage M or Ms 12-18 months old with numerical chromosomal alterations only, and in complete metastatic response at the...
- Age \< 21 years at the time of randomization
- Complete response (CR) or partial response (PR) at metastatic sites:
- Bone disease: mIBG uptake completely resolved or SIOPEN score ≤ 3 and at least 50% reduction in mIBG score (or ≤ 3 bone lesions and at least 50% reduction in number of FDG- PET-avid bone lesions for mIBG-nonavid...
- Bone marrow disease: CR and/or minimal disease (MD) according to International Neuroblastoma Response Criteria
- Other metastatic sites: CR. (after induction chemotherapy +/- surgery), except for distant lymph nodes for which PR is accepted with a possible secondary surgery
- Acceptable organ function and performance status:
- Performance status ≥ 50%.
- Hematological status: ANC\>0.5x109/L, platelets \> 20x 109/L
- Cardiac function: (\< grade 2)
- Normal chest X-Ray and oxygen saturation.
- Absence of any toxicity ≥ grade 3. 4) Sufficient collected stem cells available; a total harvest of at least 6 x 106/kg CD34+ cells, to be stored in at least 4 separate bags to administer at least 3 x 106/kg CD34+ cells...
- Written informed consent, including agreement of patient or parents/legal guardian for minors, to enter the R-HDC randomisation.
- Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
- Patients should be able and willing to comply with study visits and procedures as per protocol. In case of parents'/patient's refusal, or insufficient stem cells, collection for tandem HDC but with a minimum of 3 x 106...
- In case of no local macroscopic disease, all patients will receive 21,6-Gy radiotherapy to the pre-operative tumour bed
- In case of local macroscopic residual disease, patients will be eligible to R-RTx if the following criteria are met:
- No evidence of disease progression after HDC/ASCR.
- Interval between the last ASCR and radiotherapy start between 60 and 90 days.
- Performance status greater or equal 50%.
- Hematological status: ANC \>0.5x109/L, platelets \> 20x109/L.
- Written informed consent, including agreement of patient or parents/legal guardian for minors, to enter the R-RTx randomisation.
- Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
- Patients should be able and willing to comply with study visits and procedures as per protocol. In case of parents'/patient's refusal of the randomisation, the patient will receive 21.6 Gy radiotherapy to the...
- Insufficient metastatic response at the end of induction chemotherapy, defined as:
- SIOPEN score \> 3 or less than 50% reduction in mIBG score (or \> 3 bone lesions or less 50% reduction in number of FDG-PET-avid bone lesions for mIBG-non avid tumours) OR
- Bone marrow disease: SD according to International Neuroblastoma Response Criteria OR
- Other metastatic sites: PR or SD. For distant lymph nodes: PR and not resectable or SD.
- Performance status ≥ 50%.
- Hematological status: ANC\>0.75x109/L without G-CSF for at least 48 hours (or ANC ≥ 0.50 x 109 /L in case of bone marrow involvement), platelets \> 50x 109/L and rising, without platelets transfusion for 72 hours.
- AST or ALT ≤7.5 ULN and total bilirubin ≤1.5 ULN. In patients with liver metastases, total bilirubin ≤2.5 ULN is allowed.
- No active infection;
- No grade \>2 gastrointestinal toxicity.
- No grade ≥ 3 toxicity related to previous treatment.
- Oxygen saturation \> 94% Non-inclusion criteria for HR-NBL2:
- Any negative answer concerning the HR-NLB2 inclusion criteria
- Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving his consent.
- Participating in another clinical study with an IMP while on study treatment.
- 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 the study drugs
- Concomitant self-medication medicine that in the investigator opinion could interact with study treatments, including herbal medicine (e.g. St John's Wort (Hypericum Perforatum). Non-inclusion criteria specific to the...
- Urinary tract obstruction ≥ grade 3
- Heart failure or myocarditis ≥ grade 2, any arrhythmia or myocardial infection
- Peripheral motor or sensory neuropathy ≥ grade 3
- Demyelinating form of Charcot-Marie-Tooth syndrome
- Hearing impairment ≥ grade 2
- Concurrent prophylactic use of phenytoin
- Cardiorespiratory disease that contraindicates hyperhydration Non-inclusion criteria common to all randomisations (R-I, R-HDC, and R-RTx):
- Any negative answer concerning the inclusion criteria of R-I or R- HDC or R-RTx will render the patient ineligible for the corresponding therapy phase randomisation. However, these patients may remain on study and be...
- Liver function: Alanine aminotransferase (ALT) \> 3.0 x ULN and blood bilirubin \> 1.5 x ULN (toxicity ≥ grade 2). In case of toxicity ≥ grade 2, call national principal investigator study coordinator to discuss the...
- Renal function: Creatinine clearance and/or GFR \< 60 ml/min/1.73m² (toxicity ≥ grade 2). If GFR \< 60ml/min/1.73m², call national principal investigator study coordinator to discuss about the treatment.
- Dyspnea at rest and/or pulse oximetry \<95% in air (only for R-HDC, and R-RTx)
- Any uncontrolled intercurrent illness or infection that in the investigator opinion would impair study participation.
- Concomitant use with yellow fever vaccine and with live virus or bacterial vaccines.
- Patient allergic to peanut or soya. Non-inclusion criteria to R-HDC: \- Any negative answer concerning the R-HDC inclusion criteria Non-inclusion criteria to chemoimmunotherapy arm: \- Any negative answer concerning the...
The study team makes the final eligibility decision.
Where it's taking place
- Sydney, Randwick, Australia
- Clayton, Australia
- Nedlands, Australia
- New Lambton Heights, Australia
- Sydney, Australia
- Westmead, Australia
- Graz, Austria
- Innsbruck, Austria
- Linz, Austria
- Salzburg, Austria
- Vienna, Austria
- Brussels, Belgium
- Ghent, Belgium
- Leuven, Belgium
- Liège, Belgium
- Prague, Prague, Czechia
- Brno, Czechia
- Aarhus, Denmark
- Copenhagen, Denmark
- Odense, Denmark
+ 102 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, up to 21 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Sydney, Randwick, Australia; Clayton, Australia; Nedlands, Australia; New Lambton Heights, Australia; Sydney, Australia; Westmead, Australia and 116 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.