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

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.

Study Overview

• Status: Unknown
• Conditions: Brain Tumors
• Intervention / Treatment: Drug: HDCT 1(TTC), HDCT2(MEC)

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 Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daehangno, Jongno-gu
    • Seoul, Daehangno, Jongno-gu, Korea, Republic of
      • Recruiting
      • Seoul National University Hospital
      • Contact: Hyery Kim, MD; Phone Number: 82 2 2072 0177; Email: taban@hanmail.net
      • Contact: Hyoung Jin Kang, MD, ph.D; Phone Number: 82 2 2072 3304; Email: kanghj@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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.

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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: Carboplatin; Topotecan; Etoposide; Melphalan; Thiotepa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): February 1, 2014
• Study Completion (Anticipated): February 1, 2014

Study Registration Dates

• First Submitted: April 20, 2011
• First Submitted That Met QC Criteria: April 26, 2011
• First Posted (Estimate): April 27, 2011

Study Record Updates

• Last Update Posted (Estimate): November 19, 2013
• Last Update Submitted That Met QC Criteria: November 17, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: carboplatin; Stem cell transplantation; etoposide; topotecan; melphalan; thiotepa; Brain tumors
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Etoposide; Melphalan; Topotecan; Thiotepa
• Other Study ID Numbers: SNUCH-SCT-1102