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

NCT ID: NCT01535183

Last Updated: 2014-07-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2016-12-31

Brief Summary

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.

Conditions

Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Irinotecan

Group Type: EXPERIMENTAL

Irinotecan combination chemotherapy

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Camptosar (Pfizer) or Campto (Yakult Honsha)

Eligibility Criteria

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.

• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hyoung Jin Kang, M.D., ph.D

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

Seoul National University Hospital

Seoul, Chongno-gu, South Korea

Site Status: RECRUITING

Countries

South Korea

Facility Contacts

Hyoung Jin Kang, M.D., Ph.D

Role: primary

kanghj@snu.ac.kr

82-2-2072-3304

Hyery Kim, M.D.

Role: backup

taban@hanmail.net

82-2-2072-3452

Other Identifiers

SNUCH-1201

Identifier Type: -

Identifier Source: org_study_id