Cilengitide and Metronomic Temozolomide for Relapsed or Refractory High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas in Children and Adolescents

• Status: Terminated
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the efficacy of a combined treatment with cilengitide and metronomic oral temozolomide as measured by 6 months overall survival (OS) after diagnosis of relapse or tumour progression in children and adolescents with relapsed or refractory high-grade malignant glioma and diffuse intrinsic pontine glioma.

Secondary objectives include:

1. To evaluate the safety and toxicity of the study treatment by common toxicity criteria (CTC; version 4.0).

2. To assess

• the response rates at 6 months (continuous complete response = CCR, complete response = CR, partial response = PR, stable disease = SD, progressive disease = PD) and

• progression-free survival (PFS) at 6 months, and

• response rates, OS, and PFS at 12 months after relapse diagnosis or diagnosis of tumor progression. Response will be presented including histopathological variants.

3. To assess the pharmacokinetics of cilengitide administered as part of the study treatment.

Indication and study population for this trial:

Treatment of relapsed or refractory high grade gliomas and diffuse intrinsic pontine gliomas in paediatric patients ≥ 3 years and < 18 years of age.

Patients included in the study receive

• Cilengitide 1800 mg/m² i.v. twice weekly

• Temozolomide 75 mg/m²/d p.o. for 6 weeks, followed by 1 week rest with a mandatory platelet-count dependent dose adaptation rule: mandatory blood counts twice weekely: Platelets ≥ 100 000/µl (≥ 100 Gpt/l): 75 mg/m², platelets ≥ 50 000 - < 100 000/µl (≥ 50
• <100 Gpt/l): 50 mg/m², platelets < 50 000/µl (<50 Gpt/l): stop temozolomide until platelet recovery ≥ 100 000/µl (≥100 Gpt/l)

• Study treatment in the individual patient is scheduled for 1 year unless tumor progression or excessive toxicity occurs. However, study treatment may be extended beyond 1 year upon individual decision.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Martin-Luther-Universität Halle-Wittenberg
• Collaborators: Merck KGaA; Merck KGaA, Darmstadt, Germany
• Treatments: Dacarbazine; Temozolomide

Criteria

Inclusion Criteria:

1. Diagnosis of high-grade malignant glioma confirmed by central neuropathological review (last MRI diagnosis not older than 4 weeks) - including glioblastoma multiforme (WHO IV), anaplastic astrocytoma (WHO III), anaplastic oligodendroglioma (WHO III), anaplastic oligoastrocytoma (WHO III), anaplastic pilocytic astrocytoma (WHO III), anaplastic ganglioglioma (WHO III), anaplastic pleomorphic xanthoastrocytoma (analogous to WHO III), giant cell glioblastoma (WHO IV), and gliosarcoma (WHO IV) - or diagnosis of diffuse intrinsic pontine glioma confirmed by central neuroradiological review - refractory to standard treatment, or relapsed or progressive after first-line therapy.

2. Patient aged 3 years and older but under 18 years at time of relapse diagnosis

3. Written informed consent of the patient (mandatory from 15 years of age) or the parents (mandatory till 18 years of age).

Exclusion Criteria:

1. Known hypersensitivity or contraindication to any study drugs

2. Other (simultaneous) malignancies

3. Pregnancy and / or lactation

4. Patients who are sexually active refusing to use effective contraception (oral contraception, intrauterine devices, barrier method of contraception in conjunction with spermicidal jelly or surgical sterile)

5. Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial

6. Severe concomitant diseases (e.g. immune deficiency syndrome) or HIV infection

7. Severe psychological disease or neurological damage without possibility to communicate

8. Clinical signs of intracranial pressure

9. Intracerebral hemorrhage or history of intracerebral hemorrhage

10. Requirements for laboratory test results not older than 2 weeks before patient´s inclusion:

Platelets < 100 000/µl (< 100 Gpt/l) PT, INR and PTT above normal range Absulute neutrophil count ≤ 1 500/µl (< 1,5 Gpt/l) Hemoglobin < 10g/dl (< 6,4 mmol/L) Serum creatinine ≥ 1,5 x upper limit of normal range or creatinine clearance rate ≤ 60 ml/min/m2 (corrected for body surface area) Total bilirubin ≥ 1,5 x upper limit of normal range SGOT (ASAT) and SGPT (ALAT) ≥ 2,5 x upper limit of normal range Alkaline phosphatase ≥ 2,5 x upper limit of normal range

11. Hereditary Intrinsic Platelet Disorders

12. Ongoing irradiation or chemotherapy (within the last 4 weeks)

13. Estimated life expectancy of less than 2 months