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

Condition(s) studied

Investigational drug(s) / intervention(s)

Bevacizumab: 10mg/kg, intravenous (iv), biweekly, 2 years

Thalidomide: 3mg/kg, oral, daily, 2 years

Celecoxib: 50-400mg, oral bid, daily, 2 years

Fenofibric acid: 90mg/m2, oral, daily, 2 years

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

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

Etoposide: 0.5mg, intraventricular, day 1-5, every four weeks, alternating with intraventricular cytarabine, 2 years

Cytarabine: 16-30mg, intraventricular twice weekly for two weeks out of every four weeks, alternating with intraventricular etoposide phosphate, 2 years

Temozolomide (TMZ): Stratum IV; 150mg/m2, day 1-5 every four weeks, 1 year

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

Study 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.

Eligibility

Primary outcome measure(s)

• Efficacy — 8 years
  Response rate (Complete remission, partial response, stable disease =\[CR+PR+SD\]/n) 6 months after start of antiangiogenic treatment

Trial sites (22)

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