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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Seoul National University Hospital
Sponsor:
Information provided by (Responsible Party):
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01535183
First received: February 7, 2012
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Brain Tumor
Drug: Irinotecan combination chemotherapy
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • 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

    1. Complete Response : disappearance of all enhancing tumor
    2. Partial Remission : more than 50 percentage decrease in the tumor measurement compared with the baseline scan
    3. Stable Disease : includes changes that do not meet criteria for CR, PR, or progressive disease (PD)
    4. 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 40
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)
Arms Assigned Interventions
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 Name: Camptosar (Pfizer) or Campto (Yakult Honsha)

  Eligibility

Ages Eligible for Study:   up to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535183

Locations
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    kanghj@snu.ac.kr   
Contact: Hyery Kim, M.D.    82-2-2072-3452    taban@hanmail.net   
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Hyoung Jin Kang, M.D., ph.D Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01535183     History of Changes
Other Study ID Numbers: SNUCH-1201
Study First Received: February 7, 2012
Last Updated: July 11, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:
irinotecan
brain tumor
pediatrics
salvage therapy
chemotherapy

Additional relevant MeSH terms:
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cyclophosphamide
Irinotecan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014