Genomics-Based Target Therapy for Children With Relapsed or Refractory Malignancy

Genomics-Based Target Therapy for Children With Relapsed or Refractory Malignancy

The purpose of this study is to evaluate the efficacy and feasibility of combination chemotherapy with target agents according to the result of targeted deep sequencing in pediatric patients with relapsed/refractory solid tumor or AML.

Outcome of pediatric cancer has been improved substantially over the past few decades, but the prognosis of relapsed/refractory pediatric cancer still remains poor. Advances in genomic technologies have improved the ability to detect diverse somatic and germline genomic aberrations of cancer patients, and it has been incorporated in the clinical management of cancer.

Samsung Genomic Institute developed a targeted next-generation sequencing (NGS) platform, CancerSCAN™, which can detect clinically significant genomic aberrations of tumors. In this study, tumor samples of refractory/relapsed pediatric cancer patients will be tested with CancerSCAN™ and the patients will receive combination chemotherapy with matched single-targeted agent or multi-targeted receptor tyrosine kinase inhibitor according to the result of CancerSCAN™.

I. Relapsed/refractory solid tumor

• Perform CancerSCAN™ at enrollment
• Conventional chemotherapy (ifosfamide, carboplatin, etoposide) with matched single-targeted agent (axitinib, crizotinib, dasatinib, erlotinib, everolimus, imatinib, pazopanib, ruxolitinib, sorafenib, vandetanib, vemurafenib, or trastuzumab) or multi-targeted receptor tyrosine kinase inhibitor (pazopanib or sorafenib) according to the result of CancerSCAN™

II. Relapsed/refractory AML

• Perform CancerSCAN™ at enrollment
• Conventional chemotherapy (fludarabine, cytarabine) with matched single-targeted agent (axitinib, crizotinib, dasatinib, erlotinib, everolimus, imatinib, pazopanib, ruxolitinib, sorafenib, vandetanib, vemurafenib, or trastuzumab) or multi-targeted receptor tyrosine kinase inhibitor (pazopanib or sorafenib) according to the result of CancerSCAN™

Inclusion Criteria:

• Under 18 years of age at initial diagnosis
• Patients with refractory/relapsed solid tumor or AML (Solid tumor: Stable or progressive disease after 1st-line treatment or relapse; AML: Persistence after 2 cycles of induction chemotherapy or relapse)
• Patient with tumor sample which is adequate for targeted deep sequencing

Exclusion Criteria:

• Patients who had salvage chemotherapy previously
• Patients with organ dysfunction as follows (creatinine elevation ≥ 3 x upper limit of normal (ULN), ejection fraction <40%, significant arrhythmia or conduction disturbance)
• Patients who are not eligible to have scheduled treatment due to the other significant impaired organ function
• Patients whose tumor samples are not sufficient for targeted deep sequencing
• Pregnant or nursing women