Tandem High Dose Chemotherapy and Autologous Stem Cell Rescue for High Risk Pediatric Brain Tumors

Sponsor

Seoul National University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01342237

Collaborator

(none)

Enrollment

Location

Arm

35.1

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators plan to improve event free survival rate and reduce treatment related toxicities of pediatric patients with high risk/recurrent CNS tumors by administrating tandem high dose chemotherapy and autologous stem cell rescue.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors	Drug: HDCT 1(TTC), HDCT2(MEC)	Phase 2

Detailed Description

High risk/recurrent central nervous system (CNS) tumors have a poor prognosis so that tandem high dose chemotherapy (HDCT) with hematopoietic progenitor stem cell rescues has been chosen as potentially curative therapy. Many institutions have used carboplatin, thiotepa, etoposide (CTE) for conditioning regimen of 1st HDCT and cyclophosphamide, melphalan (CM) for conditioning regimen of 2nd HDCT. Our institution applied this regimen to the 38 pediatric patients with high risk brain tumor since 1996. Although the 3 year overall survival rate and event free survival rate were improved to 69% and 47.9%, respectively, the results showed relatively high treatment related mortality (TRM) rate of 21%. Toxicity of this tandem regimen was also reported as being high up to 32% in other researches as well so that this regimen is considered not feasible due to toxicity. In this study, the investigators plan to improve event free survival rate and reduce treatment related toxicities of pediatric patients with high risk/recurrent CNS tumors by administrating tandem high dose chemotherapy and autologous stem cell rescue with topotecan, thiotepa, carboplatin (TTC) for 1st HDCT and melphalan, etoposide, carboplatin (MEC) for 2nd HDCT.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Mar 1, 2011

Anticipated Primary Completion Date :

Feb 1, 2014

Anticipated Study Completion Date :

Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: topotecan	Drug: HDCT 1(TTC), HDCT2(MEC) TTC Topotecan (2 mg/m2 once daily i.v. on days -8, -7, -6, -5, -4) Thiotepa (300 mg/m2 once daily i.v on days -8, -7, -6) Carboplatin (500 mg/m2 once daily i.v on days -5, -4, -3) (max. 700 mg/day) MEC Melphalan (140 mg/m2 once daily i.v on day -7, 70 mg/m2 once daily i.v on day -6) Etoposide (200 mg/m2 once daily i.v on days -8, -6) Carboplatin (350 mg/m2 once daily i.v on days -8, -7, -6, -5) Other Names: Topotecan Thiotepa Carboplatin Melphalan Etoposide

Arm

Intervention/Treatment

Experimental: topotecan

Drug: HDCT 1(TTC), HDCT2(MEC)

TTC Topotecan (2 mg/m2 once daily i.v. on days -8, -7, -6, -5, -4) Thiotepa (300 mg/m2 once daily i.v on days -8, -7, -6) Carboplatin (500 mg/m2 once daily i.v on days -5, -4, -3) (max. 700 mg/day) MEC Melphalan (140 mg/m2 once daily i.v on day -7, 70 mg/m2 once daily i.v on day -6) Etoposide (200 mg/m2 once daily i.v on days -8, -6) Carboplatin (350 mg/m2 once daily i.v on days -8, -7, -6, -5)

Other Names:

Topotecan

Thiotepa

Carboplatin

Melphalan

Etoposide

Outcome Measures

Primary Outcome Measures

To evaluate event free survival rate [1 month]
To evaluate event free survival rate after high dose chemotherapy and autologous stem cell rescue in pediatric patients with high risk brain tumor

Secondary Outcome Measures

To evaluate treatment related mortality [1, 3, 6, 12 month]
To evaluate the incidence and severity of toxicity [1, 3, 6, 12 month]
To evaluate overall survival rate and relapse rate [1, 3, 6, 12 month]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

High risk pediatric brain tumors Newly diagnosed medulloblastoma, CNS PNET, ATRT, Choroid plexus carcinoma, pineoblastoma with residual tumor over 1.5cm2 after operation or with leptomeningeal seeding at diagnosis
All high grade or malignant brain tumor, age < 3 years
Recurrent embryonal brain tumors, recurrent CNS germ cell tumor
Age : no limitation
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.

Heart: a shortening fraction ≥ 28%. Liver: total bilirubin < 2 ⅹ upper limit of normal; ALT < 3 ⅹ upper limit of normal. Kidney: creatinine < 2 ⅹ normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.

Patients must lack any active viral infections or active fungal infection.
Patients (or one of parents if patients age < 20) should sign informed.

Exclusion Criteria:

Patients who do not reach partial response prior to high dose chemotherapy.
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.