High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN)
- Conditions
- Neuroblastomatumour of the peripheral autonomic symphatetic nervous system10029211
- Registration Number
- NL-OMON52860
- Lead Sponsor
- Institute Gustave Roussy
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 70
R-I eligibility criteria:
-Established diagnosis of High-Risk neuroblastoma
-No previous chemotherapyor up to 21days after one cycle of chemotherapy for
patients with localized neuroblastoma with MYCN amplification or patients with
metastatic neuroblastoma treated in emergency
-Females of childbearing potential must have a negative serum or urine
pregnancy test 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. Female patients who are lactating
must agree to stop breast-feeding.
-Written informed consent to enter the R-I randomization from patient or
parents/legal representative, patient, and age-appropriate assent.
R-HDC eligibility criteria:
-High Risk neuroblastoma, EXCEPT patients with stage M 12-18 months old with
numerical chromosomal alterations only, and in complete metastatic response at
the end of induction.
-Age < 21 years.
-Complete response (CR) or partial response (PR) at metastatic sites:
*Bone disease: MIBG uptake (or FDG-PET uptake for MIBG-nonavid tumors)
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 tumors).
*Bone marrow disease: CR and/or minimal disease (MD) according to International
Neuroblastoma Response Criteria [Park JR, JCO 2017; Burchill S, Cancer 2017].
*Other metastatic sites: complete response after induction chemotherapy +/-
surgery.
-Acceptable organ function and performance status.
*Performance status >= 50%
*Hematological status: ANC >0.5 x10^9/L, platelets > 20 x10^9/L
*Cardiac function (< grade 2)
*Normal chest X-ray and oxygen saturation
*Absence of any toxicity >= grade 3
-Sufficient collected stem cells available; minimum required: 6 x10^6 CD34+
cells/kg body weight stored in 3 separate fractions
-Written informed consent, including agreement of patient or parents/legal
guardian for minors, to enter the R-HDC randomization.
R-RTx eligibility criteria:
-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 >0.5 x10^9/L, platelets > 20 x10^9/L
-Written informed consent, including agreement of patient or parents/legal
guardian for minors, to enter the R-RTx randomization.
Non-inclusion criteria specific to the R-I randomization (RAPID COJEC/GPOH):
-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 randomizations (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
randomization. However, these patients may remain on study and be considered to
receive standard treatment of the respective therapy phase, and may be
potentially eligible for subsequent randomizations.
-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 feasibility.
-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 to
discuss about the treatment.
-Dyspnea at rest and/or pulse oximetry <95% in air.
-Any uncontrolled intercurrent illness or infection that in the investigator
opinion would impair study participation.
-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.
-Concomittant use with yellow fever vaccine and with live virus or 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
-Concomitant use with St John*s Wort (Hypericum Perforatum).
Non-inclusion criteria to R-HDC:
Patients with insufficient metastatic response at the end of induction 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,
will not be elegible for R-HDC
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>*Randomization-induction: 3-year EFS from date of R-I randomization.<br /><br>*Randomization-HDC: 3-year EFS from date of R-HDC randomization.<br /><br>*Randomization-RTx: 3-year EFS from date of RTx randomization.<br /><br>*Chemoimmunotherapy arm: Metastatic response rate after 4 cycles of TEMIRI/DB.</p><br>
- Secondary Outcome Measures
Name Time Method <p>For the whole population of high-risk neuroblastoma:<br /><br>*3- and 5-year EFS, PFS and OS calculated from diagnosis<br /><br><br /><br>For each treatment phase:<br /><br>*5-year EFS, 3- and 5-year PFS and OS calculated from the date of<br /><br>randomization/arm inclusion<br /><br>*Cumulative incidence of relapse/progression<br /><br>*Cumulative incidence of treatment related mortality and of disease related<br /><br>mortality<br /><br>*Overall response as per the new INRG response criteria [Park JR, JCO 2017]<br /><br>(including primary tumor after induction), skeletal response on MIBG, bone<br /><br>marrow response, local control<br /><br>*Therapy-related toxicity<br /><br><br /><br>For patients in the chemoimmunotherapy arm:<br /><br>*Metastatic reponse rate after 2 cycles TEMIRI/DB and 3- and 5-year EFS/PFS/OS<br /><br>from the date of initial diagnosis</p><br>