Gliomas Clinical Trial
— HGG-CilMetroOfficial 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 -
Verified date | June 2015 |
Source | Martin-Luther-Universität Halle-Wittenberg |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 28 |
Est. completion date | April 2014 |
Est. primary completion date | March 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 3 Years to 17 Years |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
Germany | University Children´s Hospital | Halle | Saxonia-Anhalt |
Lead Sponsor | Collaborator |
---|---|
Martin-Luther-Universität Halle-Wittenberg | Merck KGaA |
Germany,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Evaluation of overall survival after 6 months | 6 months | |
Secondary | Safety and toxicity of the study 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%). |
Up to 52 weeks of treatment and subsequently 30 days after end of treatment | |
Secondary | 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 | 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 |
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) | |
Secondary | Peak plasma levels of cilengitide [ng/ml] on day 1 of week 1 and day 4 of week 6 | 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) | 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 |
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