Combination Chemotherapy With Pazopanib in Children and Adolescents With Relapsed/Refractory Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of combination chemotherapy with Pazopanib in pediatric patients with relapsed/refractory solid tumor

Official Title
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Safety and Efficacy of Combination Chemotherapy With Pazopanib in Children and Adolescents With Relapsed/Refractory Solid Tumors

Conditions
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Relapsed Pediatric Solid Tumor, Refractory Pediatric Solid Tumor

Intervention / Treatment
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* Drug: Pazopanib
* Drug: Ifosfamide
* Drug: Carboplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with refractory/relapsed solid tumor (Stable or progressive disease after 1st-line treatment or relapse) Patients previously enrolled to Genomic diagnosis of pediatric tumors by NGS (IRB No. SMC 2015-11-053) Exclusion Criteria: Patients who had high-dose chemotherapy and autologous stem cell transplantation previously Patients with organ dysfunction as follows (creatinine elevation ≥ 1.5 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 with active bleeding Patients who are taking strong CYP3A4 inhibitors, QTc-prolonging drugs, antithrombotic agents, or anti-platelet agents Pregnant or nursing women Patients who can not swallow the pill

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pazopanib + conventional chemotherapy<br>Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib | Drug: Pazopanib<br>* Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib<br>Drug: Ifosfamide<br>* Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib<br>Drug: Carboplatin<br>* Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib<br>Drug: Etoposide<br>* Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Pazopanib in combination chemotherapy | Definition of dose-limiting toxicity (DLT) Hematologic DLT: delayed recovery of ANC/platelets > 42 days Grade 3 creatinine elevation, proteinuria, hyperbilirubinemia, bleeding Grade 2 arterial thrombosis Any grade 4 toxicities except hematologic toxicities | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of tumor response (neuroblastoma) | as assessed by International Neuroblastoma Response Primary tumor: CT and/or MRI; MIBG scan if available Metastatic sites: bone marrow biopsies, CT/MRI, MIBG scan CR (Complete response): No tumor (primary & metastatic) VGPR (Very good PR): Decreased by 90-99% (primary) & no tumor (metastatic) PR (Partial response): Decreased by > 50% (primary & metastatic) MR (Mixed response): > 50% reduction of any measurable lesion (primary or metastases) with < 50% reduction in any other; < 25% increase in any existing lesion SD (Stable disease): No new lesions; < 50% reduction but < 25% increase in any existing lesion. PD (Progressive disease): Any new lesion; increase of any measurable lesion by > 25% | 4 weeks | 
| Rate of tumor response (brain tumor) | - as assessed by 2-dimensional measurement (the product of the tumor's longest diameter and its longest perpendicular diameter) CR: complete disappearance of all previously measurable tumors. PR: greater than 50% decrease in tumor size SD: less than 50% reduction in tumor size or less than 25% increase in tumor size PD: greater than 25% increase in tumor size or the appearance of a new tumor | 4 weeks | 
| Rate of tumor response (other solid tumors) | - as assessed by The Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions SD: Neither sufﬁcient shrinkage to qualify for PR nor sufﬁcient increase to qualify for PD PD: At least a 20% increase in the sum of diameters of target lesions | 4 weeks |