Irinotecan Combination Chemotherapy for Refractory or Relapsed Brain Tumor in Children and Adolescents

Irinotecan, Vincristine, Etoposide, Carboplatin, and Cyclophosphamide for Refractory or Relapsed Brain Tumor in Children and Adolescents

The outcome of pediatric refractory or relapsed brain tumor is very dismal. Standard chemotherapy showed poor response to these patients. Although tandem high dose chemotherapy with hematopoietic progenitor stem cell rescues has been chosen as a potentially curative therapy for long term survival and better outcome is expected if tumor burden before transplantation reduced by chemotherapy, effective salvage chemotherapy for tumor reduction is not established yet. Irinotecan is a recently developed topoisomerase I inhibitor, and there are preclinical and phase I, II data which proved practical effects in brain tumors. In those studies, irinotecan was administered alone or in combination with one other drug.

Vincristine, etoposide, carboplatin, and cyclophosphamide have been used in many protocols for brain tumors but the result was very poor in refractory or relapsed cases. However, irinotecan can be effective with these multiple chemotherapeutic agents. According to the pilot study of irinotecan in combination with vincristine, etoposide, carboplatin and cyclophosphamide in the investigators center, 75% percent of total 12 patients reached more than stable disease, and 2 patients got long term complete remission only with this multi-agent combination chemotherapy. But the combination of irinotecan, vincristine, etoposide, carboplatin, and cyclophosphamide is not clinically studied yet especially for pediatric patients. To improve response rate and progression-free survival, the combination chemotherapy of irinotecan, vincristine, etoposide, carboplatin, and cyclophosphamide is designed for pediatric refractory or relapsed brain tumor.

Study Overview

• Status: Unknown
• Conditions: Brain Tumor
• Intervention / Treatment: Drug: Irinotecan combination chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chongno-gu
    • Seoul, Chongno-gu, Korea, Republic of, 110-744
      • Recruiting
      • Seoul National University Hospital
      • Contact: Hyoung Jin Kang, M.D., Ph.D; Phone Number: 82-2-2072-3304; Email: kanghj@snu.ac.kr
      • Contact: Hyery Kim, M.D.; Phone Number: 82-2-2072-3452; Email: taban@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of brain tumor : embryonal brain tumor (medulloblastoma, CNS PNET, ATRT, etc), intracranial germ cell tumor
• Relapse or refractory state
• Prior therapy : Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Patients are eligible 8 weeks from the day of stem cell infusion for autologous stem cell transplant, if hematological and all other eligibility criteria are met.
• Performance status: ECOG 0-2.

• Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases.

  1. Heart: a shortening fraction ≥ 28%
  2. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
  3. Kidney: creatinine <2 × normal
• Patients must lack any active viral infections or active fungal infection.
• Patients (or one of parents if patients age < 20) should sign informed consent.

Exclusion Criteria:

• Pregnant or nursing women.
• Malignant (except brain tumor) or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
• Psychiatric disorder that would preclude compliance.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.

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: Irinotecan	Drug: Irinotecan combination chemotherapy; Irrinotecan 300㎎/㎡ d0 IVS mixed with D5W 500mL over 90min with atropine (-30 min) VCR 2㎎/㎡ d0 IV push Etoposide 100㎎/㎡ d0-d2 IV over 1hr Carboplatin 450㎎/㎡ d0 IV over 8hrs Cyclophosphamide 1,000㎎/㎡ d1 IVS with mesna; Other Names: Camptosar (Pfizer) or Campto (Yakult Honsha)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate response rate (more than stable disease) of combination chemotherapy	- Response Criteria : WHO-based "Macdonald criteria", based on MRI; Complete Response : disappearance of all enhancing tumor; Partial Remission : more than 50 percentage decrease in the tumor measurement compared with the baseline scan; Stable Disease : includes changes that do not meet criteria for CR, PR, or progressive disease (PD); Progressive Disease : more than 25 percentage increase in tumor measurement compared with the lesion size that defines the nadir, or smallest measurement, in the serial studies	every 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate adverse event	- Toxicity evaluation : CTC version 4.0. A copy of the current version of the CTCAE can be downloaded from the CTEP home page (http://ctep.info.nih.gov).	during chemotherapy and every follow up (3 times a week, up to 4 weeks)
To evaluate progression-free survival	- Kaplan-Meier method will be used for analysis.	until last follow up (at least 1year)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): September 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: February 7, 2012
• First Submitted That Met QC Criteria: February 16, 2012
• First Posted (Estimate): February 17, 2012

Study Record Updates

• Last Update Posted (Estimate): July 14, 2014
• Last Update Submitted That Met QC Criteria: July 11, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: pediatrics; chemotherapy; irinotecan; brain tumor; salvage therapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: SNUCH-1201