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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed Pediatric AML; Refractory Pediatric AML; Relapsed Pediatric Solid Tumor; Refractory Pediatric Solid Tumor
• Intervention / Treatment: Drug: Erlotinib; Drug: Dasatinib; Drug: Carboplatin; Drug: Fludarabine; Drug: Imatinib; Drug: Everolimus; Drug: Sorafenib; Drug: Trastuzumab; Drug: Ruxolitinib; Drug: Cytarabine; Drug: Ifosfamide; Drug: Etoposide; Drug: Pazopanib; Drug: Crizotinib; Drug: Axitinib; Drug: Vemurafenib; Procedure: CancerSCAN™; Drug: Vandetanib

Detailed Description

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™

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Refractory/relapsed solid tumor or AML; Conventional chemotherapy (Ifosfamide carboplatin etoposide for solid tumor and fludarabine cytarabine for AML) 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™

Drug: Erlotinib; Drug: Dasatinib; Drug: Carboplatin; Drug: Fludarabine; Drug: Imatinib; Drug: Everolimus; Drug: Sorafenib; Drug: Trastuzumab; Drug: Ruxolitinib; Drug: Cytarabine; Drug: Ifosfamide; Drug: Etoposide; Drug: Pazopanib; Drug: Crizotinib; Drug: Axitinib; Drug: Vemurafenib; Procedure: CancerSCAN™; Targeted deep sequencing; Drug: Vandetanib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of event free survival	Event is defined as relapse, disease progression or treatment-related mortality.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of treatment-related adverse events as assessed by CTCAE v4.0	Up to 1 year

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Ministry of Health, Republic of Korea

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 29, 2015
• First Submitted That Met QC Criteria: December 20, 2015
• First Posted (Estimate): December 23, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Carboplatin; Etoposide; Trastuzumab; Sorafenib; Ifosfamide; Axitinib; Fludarabine; Cytarabine; Everolimus; Dasatinib; Vemurafenib; Crizotinib
• Other Study ID Numbers: 2015-08-008