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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed Pediatric Solid Tumor; Refractory Pediatric Solid Tumor
• Intervention / Treatment: Drug: Pazopanib; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 22 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pazopanib + conventional chemotherapy; Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib	Drug: Pazopanib; Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib; Drug: Ifosfamide; Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib; Drug: Carboplatin; Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib; Drug: Etoposide; Conventional chemotherapy (Ifosfamide, carboplatin, etoposide) with Pazopanib

What is the study measuring?

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 scanCR (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 lesionSD (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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2018
• Primary Completion (ANTICIPATED): July 1, 2023
• Study Completion (ANTICIPATED): July 1, 2025

Study Registration Dates

• First Submitted: July 23, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (ACTUAL): August 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 19, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Carboplatin; Etoposide; Ifosfamide
• Other Study ID Numbers: 2017-11-147

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No