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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

N/A - 19 Years

Healthy Volunteers

Not accepted

Interventions

• Bevacizumab — DRUG
  10mg/kg, intravenous (iv), biweekly, 1 year
• Thalidomide — DRUG
  3mg/kg, oral, daily, 1 year
• Celecoxib — DRUG
  50-400mg, oral bid, daily, 1 year
• Fenofibric acid — DRUG
  90mg/m2, oral, daily, 1 year
• Etoposide — DRUG
  35-50 mg/m2, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
• Cyclophosphamide — DRUG
  2.5mg/kg, oral, alternating 21-day cycles of daily oral etoposide and cyclophosphamide, 1 year
• Etoposide phosphate — DRUG
  0.5mg, intrathecal, day 1-5, every four weeks, alternating with intrathecal liposomal cytarabine, 1 year
• Cytarabine — DRUG
  16-30mg, intrathecal, twice weekly for two weeks out of every four weeks, alternating with intrathecal etoposide phosphate, 1 year
• Temozolomide (TMZ) — DRUG
  Stratum IV; 150mg/m2, day 1-5 every four weeks
• Irinotecan — DRUG
  Stratum IV; 50mg/m2, day 1-5 every four weeks

Study Details

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.

Key Dates

Start date

Apr 30, 2014

Status verified

Feb 2026

Primary completion

Apr 30, 2030

Completion

Apr 30, 2030

Study Design

Enrollment

232 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Other: Standard Arm (Stratum II, III, IV, V)
  Etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt
• Experimental: Experimental arm (Stratum IV)
  Temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt

Primary Outcome Measure

Efficacy [ Time Frame: 8 years ]

Central Contacts

• Andreas Peyrl, MD
  +43 1 40400
  [email protected]
• Amedeo A Azizi, MD
  +43 1 40400
  [email protected]

Locations (4)

Find similar trials in Chicago, IL

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