Clinical trial NCT01535183: Irinotecan Combination Chemotherapy for Refractory or Relapsed Brain Tumor in Children and Adolescents
Official title: Irinotecan, Vincristine, Etoposide, Carboplatin, and Cyclophosphamide for Refractory or Relapsed Brain Tumor in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain Tumor
Keywords: irinotecan
brain tumor
pediatrics
salvage therapy
chemotherapy
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2012-02-17
Enrollment: 40
Sex: ALL
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: To evaluate response rate (more than stable disease) of combination chemotherapy
timeFrame: every 3 months
Secondary outcomes:
measure: To evaluate adverse event
timeFrame: during chemotherapy and every follow up (3 times a week, up to 4 weeks)
measure: To evaluate progression-free survival
timeFrame: until last follow up (at least 1year)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Chongno-gu
Study officials:
affiliation: Seoul National University Hospital
name: Hyoung Jin Kang, M.D., ph.D
role: PRINCIPAL_INVESTIGATOR
References: