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Prospective, Open Label, Randomized Phase II Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-risk Neuroblastoma

Phase 2
25 Years
Not Enrolling
Neuroblastoma Recurrent

Thank you

Trial Information

Prospective, Open Label, Randomized Phase II Trial to Assess a Multimodal Molecular Targeted Therapy in Children, Adolescent and Young Adults With Relapsed or Refractory High-risk Neuroblastoma

Inclusion Criteria:

Patients with relapsed high-risk neuroblastoma (stage IV and all MYCN
pos. stages) or progressive disease during primary treatment (=rNB) and all of the
following criteria will be considered for admission to the clinical trial:

- Children, adolescents and young adults less than 25 years

- Signed written informed consent

- Females of childbearing age must have a negative urine pregnancy test prior to
starting the study drug. The first pregnancy test must be performed within 10-14 days
prior to the start of the study drug and the second pregnancy test must be performed
within 24 hours prior to the start of study drug. The subject may not receive the
study drug until the investigator has verified that the results of these pregnancy
tests are negative.

- Females of childbearing age must comply with the institutional standards of birth
control with a pearl index <1%. Contraception must be started at least four weeks
before the start of the investigational therapy.

- Females of childbearing age must be willing to abstain from breastfeeding for the
duration of the clinical trial and for at least 30 days after discontinuation of the
clinical trial.

- Males must agree not to father a child and must use latex condom during any sexual
contact with women of childbearing age during and for 6 months after therapy ends or
is stopped, even if they have undergone successful vasectomy.

- Willing and able to complete the clinical trial procedures, as described in the

- Non-smoker for at least the previous 3 months. Smoking is not allowed during the
entire study period

- Abstain from alcohol within the last 24 hours before screening and before admission
to the clinical trial center as well as during the entire clinical trial. The regular
daily ethanol intake has to be less than 20g/day for at least the previous three

- Patients are required to have an absolute neutrophil count (ANC) ≥ 500/µL, hemoglobin
≥8g/dL (transfusion permitted), and an unsupported platelet count ≥30,000/µL unless
extensive bone marrow involvement was documented

- Weight ≥ 10 kg

Exclusion Criteria:

- Pregnancy, nursing

- Patients who suffered from a thrombotic event and need anticoagulation (i.e. coumadin
derivatives or low molecular weight heparin derivatives, LMWH)

- Patients with cardiac arrhythmias especially prolonged QT

- Patients with chronic inflammatory bowel diseases and/or bowel obstruction

- Patients with bilirubin serum levels 1,5 fold above the upper normal limit

- Vaccination with a live virus vaccine during the clinical trial

- Impaired liver function and/or impaired renal function (hepatic and renal index
parameter two times above normal range; see below)

- Potentially unreliable subjects, probably non compliant subjects and those judged by
the investigator to be unsuitable for the study

- Doubts about the patient's cooperation

- Any contraindications or known hypersensitivity to the IMPs or to any of the other
components: (see SPC ("Fachinformation", appendix)

- Known allergic reactions to the treatment medication

- Patients who were treated with radiation and/or chemotherapy for any other
oncological condition

- Participation in any other phase I to III trial

- Sexually active patients who refuse to use contraception according to the
institutional requirements

- Patients with extremely poor general condition (Karnofsky or Lansky score <50%)

- Neutrophil count (ANC) <500/µL, hemoglobin <8g/dL (transfusion permitted), and an
unsupported platelet count <30 000/µL

- 12-lead ECG with QTc>500 msec / QTc>60 msec baseline

- Weight <10 kg

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary endpoint is progression-free survival (PFS)

Outcome Description:

The primary objective of this trial is the evaluation of progression-free survival of rNB in children, adolescents and young adults, comparing a multimodal treatment regimen consisting of temozolomide (T), irinotecan (I), rapamycin (R) and dasatinib (S) against irinotecan (I) and temozolomide (T) (I/T) alone

Outcome Time Frame:

Time interval from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks

Safety Issue:


Principal Investigator

Selim Corbacioglu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Regensburg, Department of Pediatric Hematology and Oncology


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

July 2013

Completion Date:

December 2018

Related Keywords:

  • Neuroblastoma Recurrent
  • neuroblastoma
  • molecular targeted therapy
  • protein kinase inhibitor
  • mTOR Inhibitor
  • cytostatic topoisomerase-I-inhibitor
  • temozolomide
  • irinotecan
  • dasatinib
  • rapamycin
  • Neuroblastoma