Cilengitide and Metronomic Temozolomide for Relapsed or Refractory High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas in Children and Adolescents (HGG-CilMetro)
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:
- To evaluate the safety and toxicity of the study treatment by common toxicity criteria (CTC; version 4.0).
- 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.
- 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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Cilengitide and Metronomic Temozolomide for Relapsed or Refractory High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas in Children and Adolescents - A Phase II Study HIT-HGG-CilMetro - A Clinical Phase II Trial of the HIT-HGG Study Group -|
- Efficacy of a combined treatment with cilengitide and temozolomide as measured by 6 months overall survival after diagnosis of relapsed or refractory high grade glioma or diffuse intrinsic pontine glioma in children and adolescents [ Time Frame: 6 months ]Evaluation of overall survival after 6 months
- Safety and toxicity of the study treatment [ Time Frame: Up to 52 weeks of treatment and subsequently 30 days after end of treatment ]
Evaluation of safety and toxicity of the study treatment by NCI Common Toxicity Criteria (CTC; version 4.0) for up to 30 days after the end of study treatment which may last up to 52 weeks.
Toxic events defined as CTC grade 4 toxicities and deaths caused by therapy (CTC grade 5) excluding haematological toxicities (CTC grade 1-4)will be immediately assessed after documentation, and probability for such a toxic event statistically evaluated to ensure that this probability is within the predefined range (p1=15%).
- Response rates (RR) at 6 months, progression-free survival (PFS) at 6 months, and RR, overall survival (OS), and PFS at 12 months after relapse diagnosis or diagnosis of tumor progression [ Time Frame: Response rates and progression-free survival at 6 and 12 months, overall survival at 12 months (Trial subjects will be followed up for at least 1 year and 30 days after study entry) ]
Evaluation of RR (continuous complete response = CCR, complete response = CR, partial response = PR, stable disease = SD, progressive disease = PD) by MRI and PFS (defined as survival from date of first progression/relapse to first documented date of second progression/relapse) after 6 and 12 months.
Evaluation of OS after 12 months
- Peak plasma levels of cilengitide [ng/ml] on day 1 of week 1 and day 4 of week 6 [ Time Frame: Day 1 of treatment week 1: Immediately before and immediately after as well as 2, 4, and 7 hours after end of cilengitide administration; day 4 of treatment week 6: 2 hours after end of cilengitide adminstration ]Assessment of cilengitide serum levels [ng/ml] by a validated liquid chromatograpy tandem mass spectrometry assay on day 1 of week (before, immediately after, and 2, 4, 7 hours after cilengitide administration) and day 4 of week 6 (2 hours after cilengitide administration)
|Study Start Date:||January 2012|
|Study Completion Date:||April 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: Cilengitide and metronomic temozolomide
Cilengitide 1800 mg/m² i.v. twice weekly and Temozolomide 75 mg/m²/d p.o. for 6 weeks, followed by 1 week rest with a mandatory platelet-count dependent dose adaptation rule
Cilengitide 1800 mg/m² i.v. twice weekly with a mandatory platelet-count dependent dose adaptation rule
Other Name: EMD 121974Drug: Temozolomide
Temozolomide 75 mg/m²/d p.o. for 6 weeks, followed by 1 week rest with a mandatory platelet-count dependent dose adaptation rule
Other Name: Temodal
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01517776
|University Children´s Hospital|
|Halle, Saxonia-Anhalt, Germany, 06120|
|Study Chair:||Christof M. Kramm, MD||University Children´s Hospital, Halle, Germany|