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

Brain Tumors Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01342237
• Other study ID #: SNUCH-SCT-1102
• Status: Recruiting
• Phase: Phase 2
• First received: April 20, 2011
• Last updated: November 17, 2013
• Start date: March 2011
• Est. completion date: February 2014

Study information

• Verified date: November 2013
• Source: Seoul National University Hospital
• Contact: Hyoung Jin Kang, MD, PhD
• Phone: 82 2 2072 3304
• Email: kanghj[@]snu.ac.kr
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. 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

2. All high grade or malignant brain tumor, age < 3 years

3. Recurrent embryonal brain tumors, recurrent CNS germ cell tumor

4. Age : no limitation

5. Performance status : ECOG 0-2.

6. 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 ? upper limit of normal; ALT < 3 ? upper limit of normal. Kidney: creatinine < 2 ? normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.

7. Patients must lack any active viral infections or active fungal infection.

8. Patients (or one of parents if patients age < 20) should sign informed.

Exclusion Criteria:

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

2. Pregnant or nursing women.

3. Malignant (except brain tumor) or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.

4. Psychiatric disorder that would preclude compliance.

5. 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: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors

Intervention

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)

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul	Daehangno, Jongno-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 event free survival rate	To evaluate event free survival rate after high dose chemotherapy and autologous stem cell rescue in pediatric patients with high risk brain tumor	1 month	No
Secondary	To evaluate treatment related mortality		1, 3, 6, 12 month	No
Secondary	To evaluate the incidence and severity of toxicity		1, 3, 6, 12 month	No
Secondary	To evaluate overall survival rate and relapse rate		1, 3, 6, 12 month	No