Multimodal Molecular Targeted Therapy to Treat Relapsed or Refractory High-risk Neuroblastoma
Status:
Completed
Trial end date:
2020-09-30
Target enrollment:
Participant gender:
Summary
Children, adolescents and young adults with high risk relapsed or treatment refractory
neuroblastoma (rNB) represent a group of patients with dismal prognosis for whom a
recommended standard salvage therapy is currently not available.
The multimodal metronomic approach combining molecular targeted drugs (rapamycin and
dasatinib) with conventional chemotherapy (irinotecan and temozolomide) will be investigated
in a randomized fashion as new treatment strategy for patients with rNB. The intention is to
assess the therapeutic benefit of molecular targeted drugs for the treatment of rNB.
The combination of irinotecan and temozolomide showed activity in the treatment of several
solid organ tumors, brain tumors and neuroblastoma. In one study rNB patients received a
median of 5 courses of 5 days irinotecan and temozolomide every 3 to 4 weeks with a
cumulative dose of 35% lower than in the RIST design. 33% had disease regression with 8% CR
or PR. A phase II study in rNB also using irinotecan and temozolomide with a substantially
lower intensity showed a response rate of 15%.
The combination of a mTOR inhibitor with a multi-kinase inhibitor demonstrated in preclinical
studies a synergistic effect on cell cycle arrest, apoptosis and sensitization for radio- and
chemotherapy. It is assumed that this combination of molecular targeted drugs with a
tolerable conventional chemotherapy consisting of irinotecan and temozolomide can
substantially improve the outcome of this patient population. A group of 20 rNB patients
treated with the RIST therapy approach in a compassionate use setting showed an overall
survival of 55% at a median of 80 weeks with a tolerable adverse event profile.
Phase:
Phase 2
Details
Lead Sponsor:
University of Regensburg
Treatments:
Alkylating Agents Antineoplastic Agents Camptothecin Dacarbazine Dasatinib Everolimus Irinotecan Protein Kinase Inhibitors Sirolimus Temozolomide Titanium dioxide Topoisomerase I Inhibitors