Childhood Central Nervous System Germ Cell TumorPhase 1NCT00063973
Cilengitide in Treating Children With Refractory Primary Brain Tumors
A Phase 1 study testing cilengitide and laboratory biomarker analysis in people with Childhood Central Nervous System Germ Cell Tumor and Childhood Choroid Plexus Tumor, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of cilengitide in treating children with recurrent, progressive, or refractory primary CNS tumors. Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma
- What is being tested?
- cilengitide and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2003to Mar 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Pediatric Brain Tumor Consortium
Memphis, Tennessee, 38105
About this study
Official title: Phase I Study of Cilengitide (EMD 121974) in Children With Refractory Brain Tumors
This phase I trial is studying the side effects and best dose of cilengitide in treating children with recurrent, progressive, or refractory primary CNS tumors. Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- Conditions
- Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma, Childhood Ependymoblastoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma
- Being tested
- cilengitide, laboratory biomarker analysis
- Medical subject headings
- Choroid Plexus Neoplasms, Astrocytoma, Oligodendroglioma, Familial ependymoma, Medulloblastoma, Optic Nerve Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cilengitideDrug
Also called EMD 121974
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cilengitide) | Experimental | 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 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. Receives: Drug: cilengitide; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of cilengitide
Measured: 4 weeks
Secondary outcomes (1)
Response
Reported and recorded descriptively.
Measured: Up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2003 (estimated)
- Study startJul 2003
- Primary completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood Central Nervous System Germ Cell TumorStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Tobey MacDonald, Principal investigator, Pediatric Brain Tumor Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00063973
- Sponsor's protocol ID
- NCI-2012-03175
- Other IDs
- NCI-2012-03175, CDR653715, PBTC-012, PBTC-012, U01CA081457
- Status last verified
- Sep 2013
- First submitted
- 8 Jul 2003
- Last updated
- 30 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Cilengitide (EMD 121974) in Children With Refractory Brain Tumors
- ClinicalTrials.gov ID
- NCT00063973
- Acronym / sponsor ID
- NCI-2012-03175
- Conditions
- Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma, Childhood Ependymoblastoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2003
- Primary completion
- Mar 2008 (actual)
- First posted
- 9 Jul 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial is studying the side effects and best dose of cilengitide in treating children with recurrent, progressive, or refractory primary CNS tumors. Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cilengitide) | Experimental | Drug: cilengitide, Other: laboratory biomarker analysisPatients 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 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. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cilengitideAlso: EMD 121974Given IV | Drug | Treatment (cilengitide) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (cilengitide) |
Primary outcome
MTD of cilengitide
Time frame: 4 weeks
1 secondary outcome
Response
Time frame: Up to 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tobey MacDonald principal investigator
Pediatric Brain Tumor Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cilengitide and laboratory biomarker analysis in people with Childhood Central Nervous System Germ Cell Tumor and Childhood Choroid Plexus Tumor, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD of cilengitide (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2013.