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

Brain Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01535183
• Other study ID #: SNUCH-1201
• Status: Recruiting
• Phase: Phase 2
• First received: February 7, 2012
• Last updated: July 11, 2014
• Start date: January 2012
• Est. completion date: December 2016

Study information

• Verified date: July 2014
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 19 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul	Chongno-gu

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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)	Yes
Secondary	To evaluate progression-free survival	- Kaplan-Meier method will be used for analysis.	until last follow up (at least 1year)	No