Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors

Summary

Patients with with recurrent or progressive medulloblastoma, ependymoma, atypical teratoid rhabdoid tumor (ATRT), and CNS tumors of various histologies have a very poor prognosis whether treated with conventional chemotherapy, high-dose chemotherapy with stem cell rescue, irradiation or combinations of these modalities.

Antiangiogenesis therapy has emerged as a new treatment option in solid malignancies. The frequent delivery of low doses of chemotherapy, referred to as metronomic or antiangiogenic chemotherapy, targets endothelial cells while reducing the toxicity associated with standard dose chemotherapy.

The aim of the study is to extend therapy options for children with recurrent or progressive medulloblastoma, ependymoma, ATRT, and CNS tumors of various histologies, for whom no known curative therapy exists, by prolonging survival while maintaining good quality of life.

The study will be conducted in independent strata. Stratum I (recurrent medulloblastoma): recently completed (Peyrl, 2023). Stratum II (recurrent ependymoma), III (recurrent ATRT) and V (recurrent CNS tumors of various histologies, patients with exclusion criteria and adult patients): The primary objective is to determine the response rate defined as the percentage of patients with complete response (CR), partial response (PR), stable disease (SD) or lack of recurrence at 6 months after start of antiangiogenic treatment. Stratum IV (recurrent medulloblastoma): To determine whether temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt can increase the response rate after 6 months of treatment, compared with etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt. Additionally, PFS, OS, toxicity, QoL, performance status, predictive and prognostic markers will be examined.

In stratum II and III, the study will follow an open label, single arm phase 2 design, and an open label randomized two-arm phase 2 design in Stratum IV, and the exploratory Stratum V.

Conditions

• Medulloblastoma Recurrent
• Ependymoma Recurrent
• ATRT Recurrent
• Rare CNS Tumor Recurrent

Interventions

DRUG

Temozolomide (TMZ)

Stratum IV; 150mg/m2, day 1-5 every four weeks

DRUG

Irinotecan

Stratum IV; 50mg/m2, day 1-5 every four weeks

DRUG

Bevacizumab

10mg/kg, intravenous (iv), biweekly, 1 year

DRUG

Thalidomide

3mg/kg, oral, daily, 1 year

DRUG

Celecoxib

50-400mg, oral bid, daily, 1 year

DRUG

Fenofibric acid

90mg/m2, oral, daily, 1 year

DRUG

Etoposide

35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

DRUG

Cyclophosphamide

2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year

DRUG

Etoposide phosphate

0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year

DRUG

Cytarabine

16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Principal Investigators

• Andreas Peyrl, MD · Medical University of Vienna

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-04-30

Primary Completion

2030-04-30

Completion

2030-04-30

Countries

• United States
• Austria
• Czechia
• Denmark
• France
• Norway
• Spain
• Sweden

Study Locations