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

NCT01517776 | Terminated Phase 2 DMC

• 2 other identifiers: HIT-HGG-CilMetro2009-011898-33
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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:

• 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.
• 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.

Conditions

Gliomas

Keywords

High grade glioma; Glioblastoma multiforme; Anaplastic astrocytoma; Diffuse intrinsic pontine glioma; Relapse; refractory tumour disease; Relapsed or refractory high grade gliomas and diffuse intrinsic pontine gliomas

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Safety and toxicity of the study treatment

  Up to 52 weeks of treatment and subsequently 30 days after end of treatment

• 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

  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)

• Peak plasma levels of cilengitide [ng/ml] on day 1 of week 1 and day 4 of week 6

  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

Study Arms (1)

Cilengitide and metronomic temozolomide

EXPERIMENTAL

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

Drug: Cilengitide; Drug: Temozolomide

Interventions

Cilengitide DRUG

Cilengitide 1800 mg/m² i.v. twice weekly with a mandatory platelet-count dependent dose adaptation rule

Also known as: EMD 121974

Cilengitide and metronomic temozolomide

Temozolomide DRUG

Temozolomide 75 mg/m²/d p.o. for 6 weeks, followed by 1 week rest with a mandatory platelet-count dependent dose adaptation rule

Also known as: Temodal

Cilengitide and metronomic temozolomide

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Patient aged 3 years and older but under 18 years at time of relapse diagnosis
• Written informed consent of the patient (mandatory from 15 years of age) or the parents (mandatory till 18 years of age).

You may not qualify if:

• Known hypersensitivity or contraindication to any study drugs
• Other (simultaneous) malignancies
• Pregnancy and / or lactation
• 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)
• Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial
• Severe concomitant diseases (e.g. immune deficiency syndrome) or HIV infection
• Severe psychological disease or neurological damage without possibility to communicate
• Clinical signs of intracranial pressure
• Intracerebral hemorrhage or history of intracerebral hemorrhage
• 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
• Hereditary Intrinsic Platelet Disorders
• Ongoing irradiation or chemotherapy (within the last 4 weeks)
• Estimated life expectancy of less than 2 months

Sponsors & Collaborators

• Martin-Luther-Universität Halle-Wittenberg: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

University Children´s Hospital

Halle, Saxony-Anhalt, 06120, Germany

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma; Diffuse Intrinsic Pontine Glioma; Recurrence

Interventions

Cilengitide; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christof M. Kramm, MD

  University Children´s Hospital, Halle, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator (

Study Record Dates

• First Submitted: January 11, 2012
• First Posted: January 25, 2012
• Study Start: January 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: April 1, 2014
• Last Updated: July 21, 2015

Record last verified: 2015-06

Locations

DE (1)