Irinotecan Combination Chemotherapy 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 Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Irinotecan, Vincristine, Etoposide, Carboplatin, and Cyclophosphamide for Refractory or Relapsed Brain Tumor in Children and Adolescents|
- To evaluate response rate (more than stable disease) of combination chemotherapy [ Time Frame: every 3 months ] [ Designated as safety issue: No ]
- 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
- To evaluate adverse event [ Time Frame: during chemotherapy and every follow up (3 times a week, up to 4 weeks) ] [ Designated as safety issue: Yes ]- 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).
- To evaluate progression-free survival [ Time Frame: until last follow up (at least 1year) ] [ Designated as safety issue: No ]- Kaplan-Meier method will be used for analysis.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
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 Name: Camptosar (Pfizer) or Campto (Yakult Honsha)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01535183
|Korea, Republic of|
|Seoul National University Hospital||Recruiting|
|Seoul, Chongno-gu, Korea, Republic of, 110-744|
|Contact: Hyoung Jin Kang, M.D., Ph.D 82-2-2072-3304 email@example.com|
|Contact: Hyery Kim, M.D. 82-2-2072-3452 firstname.lastname@example.org|
|Principal Investigator:||Hyoung Jin Kang, M.D., ph.D||Seoul National University Hospital|