Phase I Study of Cilengitide (EMD 121974) in Children With Refractory Brain Tumors


Phase 1
N/A
21 Years
Not Enrolling
Both
Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma, Childhood Ependymoblastoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma, Childhood Grade III Meningioma, Childhood High-grade Cerebellar Astrocytoma, Childhood High-grade Cerebral Astrocytoma, Childhood Infratentorial Ependymoma, Childhood Low-grade Cerebellar Astrocytoma, Childhood Low-grade Cerebral Astrocytoma, Childhood Medulloepithelioma, Childhood Mixed Glioma, Childhood Oligodendroglioma, Childhood Supratentorial Ependymoma, Recurrent Childhood Brain Stem Glioma, Recurrent Childhood Brain Tumor, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Medulloblastoma, Recurrent Childhood Pineoblastoma, Recurrent Childhood Subependymal Giant Cell Astrocytoma, Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor, Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Thank you

Trial Information

Phase I Study of Cilengitide (EMD 121974) in Children With Refractory Brain Tumors


PRIMARY OBJECTIVES:

I. To describe the acute and dose-limiting toxicities (DLT) and define the maximum tolerated
dose (MTD) of cilengitide (EMD 121974) when administered to children and adolescents with
refractory primary brain tumors.

SECONDARY OBJECTIVES:

I. To obtain preliminary evidence of biologic activity by determining alterations in tissue
perfusion, tumor blood flow and metabolic activity using MR perfusion, PET and MRS and
correlating these findings with changes in tumor size by volumetric MRI.

II. To characterize inter- and intra-patient variability in the pharmacokinetics of
cilengitide and to estimate cilengitide renal clearance in this patient population.

III. To characterize the pharmacogenetic polymorphisms in drug transporters (e.g., MRP4,
BCRP) and relate to cilengitide disposition.

IV. To evaluate changes in circulating endothelial cells (CECs) and circulating endothelial
precursors (CEPs) in patients treated with cilengitide, and to investigate the correlation
between changes in CECs and CEPs, plasma, serum and urine angiogenic protein levels such as
VEGF, and clinical outcome.

V. To obtain preliminary information about the efficacy of cilengitide in this patient
population.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive cilengitide (EMD 121974) IV over 1 hour twice weekly. Treatment repeats
every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cilengitide until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients are
expected to experience dose-limiting toxicity. Once the MTD is determined, 6 additional
patients are accrued and treated at that dose level for a total of 12 patients at the MTD.

Patients receiving treatment are followed weekly for the first three months then monthly for
one year or 13 courses of treatment. Patients discontinuing treatment will be followed for
resolution of all adverse events occurring while on treatment and/or within 30 days of the
last administration of study drug.

Patients will be followed for the shortest of 1) three months after the last protocol based
treatment, or 2) the date other therapy is initiated.


Inclusion Criteria:



- Patients with histological diagnosis of primary CNS tumor and evidence that the tumor
is recurrent or progressive and refractory to standard therapy, including
histologically benign CNS tumors (e.g. low-grade glioma); clinical and radiographic
evidence of a brain stem or optic pathway glioma is required in the absence of
histologic diagnosis

- Karnofsky or Modified Lansky Score ≥ 50%

- Patients with neurological deficits should have deficits that are stable for ≥ 1 week
prior to study entry

- Chemotherapy: Patients with evidence of recovery from prior therapy; no
investigational agent, including biologic agent, within two (2) weeks of study entry;
at least six (6) weeks from nitrosourea agent to study entry; at least four (4) weeks
from any myelosuppressive therapy to study entry

- Bone Marrow Transplant: Greater than six (6) months prior to study entry

- XRT: At least six (6) weeks from prior radiation therapy to study entry; greater than
three (3) months from prior craniospinal irradiation (> 24 Gy) or total body
irradiation to study entry; greater than two (2) weeks from local palliative
irradiation to study entry

- Anti-convulsants: Patients will be eligible for this study even if they are receiving
anti-convulsants

- Growth factors: Off all colony forming growth factor(s) > one (1) week prior to study
entry (G-CSF, GM-CSF, erythropoietin)

- Corticosteroids: Patients receiving corticosteroids must be receiving a stable dose
for ≥ one (1) week prior to study entry

- ANC > 1,000/μl

- Platelets > 100,000/μl (transfusion independent)

- Hemoglobin > 8.0 g/dl (may be transfused)

- Patients with bone marrow involvement may be eligible

- Creatinine < 1.5 times normal range for age

- GFR > 70 ml/min/1.73m^2

- Total bilirubin ≤ upper limit of normal for age

- SGPT (ALT) and SGOT (AST) < 2.5 times upper limit of normal

- Cilengitide was teratogenic when tested in animals; as such, female patients of
childbearing potential must have a negative serum or urine pregnancy test prior to
study entry; female patients must avoid breast feeding while on study

- Patients of childbearing potential must be willing to use a medically acceptable form
of birth control, which includes abstinence, while being treated on this study

- Signed informed consent according to institutional guidelines must be obtained prior
to patient registration

Exclusion Criteria:

- Patient must not be receiving any other anticancer or experimental drug therapy, with
the exception of corticosteroids

- Patient must have no uncontrolled infection

- Patient has no overt renal, hepatic, cardiac or pulmonary disease

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of cilengitide

Outcome Time Frame:

4 weeks

Safety Issue:

Yes

Principal Investigator

Tobey MacDonald

Investigator Role:

Principal Investigator

Investigator Affiliation:

Pediatric Brain Tumor Consortium

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03175

NCT ID:

NCT00063973

Start Date:

July 2003

Completion Date:

Related Keywords:

  • Childhood Central Nervous System Germ Cell Tumor
  • Childhood Choroid Plexus Tumor
  • Childhood Craniopharyngioma
  • Childhood Ependymoblastoma
  • Childhood Grade I Meningioma
  • Childhood Grade II Meningioma
  • Childhood Grade III Meningioma
  • Childhood High-grade Cerebellar Astrocytoma
  • Childhood High-grade Cerebral Astrocytoma
  • Childhood Infratentorial Ependymoma
  • Childhood Low-grade Cerebellar Astrocytoma
  • Childhood Low-grade Cerebral Astrocytoma
  • Childhood Medulloepithelioma
  • Childhood Mixed Glioma
  • Childhood Oligodendroglioma
  • Childhood Supratentorial Ependymoma
  • Recurrent Childhood Brain Stem Glioma
  • Recurrent Childhood Brain Tumor
  • Recurrent Childhood Cerebellar Astrocytoma
  • Recurrent Childhood Cerebral Astrocytoma
  • Recurrent Childhood Ependymoma
  • Recurrent Childhood Medulloblastoma
  • Recurrent Childhood Pineoblastoma
  • Recurrent Childhood Subependymal Giant Cell Astrocytoma
  • Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
  • Recurrent Childhood Visual Pathway and Hypothalamic Glioma
  • Astrocytoma
  • Brain Neoplasms
  • Craniopharyngioma
  • Adamantinoma
  • Ependymoma
  • Glioma
  • Medulloblastoma
  • Meningioma
  • Oligodendroglioma
  • Choroid Plexus Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Pinealoma
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Optic Nerve Glioma

Name

Location
Pediatric Brain Tumor Consortium Memphis, Tennessee  38105