Childhood High-grade Cerebellar AstrocytomaPhase 2NCT00679354
Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy
A Phase 2 study testing cilengitide, laboratory biomarker analysis and pharmacological study in people with Childhood High-grade Cerebellar Astrocytoma and Childhood High-grade Cerebral Astrocytoma, run by National Cancer Institute (NCI) at 20 sites in 2 countries.
Trial summary
This phase II trial studies how well cilengitide works in treating younger patients with recurrent or progressive high-grade glioma that has not responded to standard therapy. Cilengitide may stop the growth of tumor cells by blocking 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 High-grade Cerebellar Astrocytoma, Childhood High-grade Cerebral Astrocytoma, Recurrent Childhood Anaplastic Astrocytoma
- What is being tested?
- cilengitide, laboratory biomarker analysis and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 20 sitesin 2 countries
- Study dates
- Jun 2008to Jul 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed primary central nervous system (CNS) high-grade glioma, including any of the following:
- Glioblastoma multiforme
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- High-grade astrocytoma not otherwise specified (i.e., anaplastic ganglioglioma, anaplastic mixed glioma, or anaplastic mixed glioneuronal tumors)
- No diffuse pontine gliomas, gliomatosis cerebri, and primary spinal cord high-grade astrocytoma
Show all 56Show fewer
- Gliosarcoma
- Recurrent or progressive disease that is refractory to standard therapy
- Radiographically documented measurable disease
- Lesion must be at least twice the thickness of the image from which it is derived (e.g., 10 mm for a 5 mm slice thickness)
- No diffuse pontine gliomas
- No evidence of prior CNS bleeding
- Karnofsky performance status (PS) 50-100% (patients > 16 years of age)
- Lansky PS 50-100% (patients =< 16 years of age)
- Life expectancy >= 8 weeks
- Absolute neutrophil count (ANC) >= 1,000/μL
- Platelet count >= 100,000/μL (transfusion independent)
- Hemoglobin >= 8.0 g/dL (red blood cell [RBC] transfusions allowed)
- Creatinine clearance or radioisotope glomerular filtration rate >= 70mL/min OR serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 month to < 6 months of age)
- 0.5 mg/dL (6 months to < 1 year of age)
- 0.6 mg/dL (1 to < 2 years of age)
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4mg/dL (female) (>= 16 years of age)
- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times ULN for age
- No evidence of dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 94%, if determination is clinically indicated
- Seizure disorder is allowed provided it is well-controlled with anticonvulsants
- No uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Recovered from all prior therapy
- No more than two prior treatments for high-grade glioma (i.e., one initial treatment and one treatment for relapse)
- More than 2 weeks since prior myelosuppressive chemotherapy (>= 6 weeks for nitrosoureas)
- At least 1 week since prior non-myelosuppressive chemotherapy, immunotherapy, or biologic therapy
- At least 2 weeks since prior local palliative radiotherapy (i.e., small port) to a symptomatic non-target lesion only
- At least 3 months since prior craniospinal radiotherapy
- At least 6 weeks since prior substantial bone marrow radiotherapy
- At least 6 months since prior allogeneic stem cell transplant (SCT) or rescue
- Patients who have undergone prior allogeneic SCT and who have graft-versus-host disease (GVHD) must have controlled GVHD that is =< grade 2
- At least 1 month since prior autologous SCT
- More than 1 week since prior growth factors (> 3 weeks for pegfilgrastim [Neulasta®])
- No other concurrent anticancer therapy, including chemotherapy or immunomodulating agents
- No other concurrent experimental agents or therapies
- No concurrent alternative or complimentary therapies
- No concurrent homeopathic medicines
- No concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (aspirin)
- No concurrent steroids as anti-emetics
- Concurrent steroids for treatment of increased intracranial pressure allowed if on a stable or decreasing dose for >= 1 week before study entry
- Concurrent radiotherapy to localized painful lesions allowed provided >= 1 measurable lesion is not irradiated
Who cannot join
None listed.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States19 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60614
Palmetto Health Richland
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
New York University Langone Medical Center
New York, New York, 10016
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Kaiser Permanente-Oakland
Oakland, California, 94611
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
Montefiore Medical Center
The Bronx, New York, 10467-2490
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, 20057
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: Cilengitide (EMD 121974) (IND# 59073) in Recurrent or Progressive and Refractory Childhood High-Grade Glioma
This phase II trial studies how well cilengitide works in treating younger patients with recurrent or progressive high-grade glioma that has not responded to standard therapy. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the objective response rate to cilengitide in younger patients with recurrent or progressive high-grade glioma that is refractory to standard therapy.
SECONDARY OBJECTIVES:
- To estimate the distribution of time to progression, time to treatment failure, and time to death in these patients.
II. To estimate the rate of toxicity, especially symptomatic intratumoral hemorrhage, in these patients.
III. To evaluate the pharmacokinetics of cilengitide in plasma using a limited sampling strategy.
IV. To evaluate the pharmacogenetic polymorphisms in drug transporters (eg, breast cancer resistance protein [BCRP], P-glycoprotein [P-gp]) and relate to cilengitide disposition.
OUTLINE:
Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then periodically for 3 years.
- Conditions
- Childhood High-grade Cerebellar Astrocytoma, Childhood High-grade Cerebral Astrocytoma, Recurrent Childhood Anaplastic Astrocytoma, Recurrent Childhood Anaplastic Oligoastrocytoma, Recurrent Childhood Anaplastic Oligodendroglioma, Recurrent Childhood Brain Tumor
- Being tested
- cilengitide, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Astrocytoma, Oligodendroglioma, 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
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cilengitide) | Experimental | Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: cilengitide; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response to Cilengitide
Objective response is defined as a complete response or partial response at 4 weeks that is sustained for at least another 4 weeks, or a stable disease at 4 weeks that is sustained for at least 12 weeks while on stable or decreasing dose of corticosteroids, except when corticosteroids are being used to control hydrocephaly unrelated to tumor progression.
Measured: Up to 16 weeks
Secondary outcomes (12)
Time to Tumor Progression (TTP)
The distribution of TTP will be analyzed separately using product limit (PL) estimate.
Measured: Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years
Time to Treatment Failure (TTF)
The distribution of TTF will be analyzed separately using PL estimate.
Measured: Time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 5 years
Time to Death (TTD)
The distribution of TTD will be analyzed separately using PL estimate.
Measured: Time from study enrollment to death from any cause, assessed up to 5 years
Rate of Toxicity, Especially That of Symptomatic Intratumoral Hemorrhage (ITH) Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Rate of individual toxicity including that of symptomatic ITH will be summarized in each course of treatment using standard descriptive statistical methods.
Measured: Up to 5 years
Pharmacokinetic Parameter of Cilengitide in Plasma: Volume of Central Compartment (Vc)
Cilengitide plasma concentration-time data are fit to a compartmental pharmacokinetic model using MAP-Bayesian estimation as implemented in ADAPT II. For each patient, samples collected at different time points are used to derive one Vc value per patient.
Measured: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacokinetic Parameter of Cilengitide in Plasma: Elimination Rate Constant (Ke)
Cilengitide plasma concentration-time data are fit to a compartmental pharmacokinetic model using MAP-Bayesian estimation as implemented in ADAPT II. For each patient, samples collected at different time points are used to derive one Ke value per patient.
Measured: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacokinetic Parameter of Cilengitide in Plasma: Half-life (t1/2)
Cilengitide plasma concentration-time data are fit to a compartmental pharmacokinetic model using MAP-Bayesian estimation as implemented in ADAPT II. For each patient, samples collected at different time points are used to derive one t1/2 value per patient.
Measured: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacokinetic Parameter of Cilengitide in Plasma: Systemic Clearance (Cl)
Cilengitide plasma concentration-time data are fit to a compartmental pharmacokinetic model using MAP-Bayesian estimation as implemented in ADAPT II. For each patient, samples collected at different time points are used to derive one Cl value per patient.
Measured: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by AUC
Cilengitide systemic exposure as measured by AUC is used in this genotype-phenotype analysis. The ABCB1 (P-glycoprotein; P-gp) Exon 26 genotype is coded as 0/1/2 based on the number of T alleles.
Measured: At baseline
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
Cilengitide systemic exposure as measured by systemic clearance is used in this genotype-phenotype analysis. The ABCB1 (P-glycoprotein; P-gp) Exon 26 genotype is coded as 0/1/2 based on the number of T alleles.
Measured: At Baseline
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by AUC
Cilengitide systemic exposure as measured by AUC is used in this genotype-phenotype analysis. The ABCG2 (breast cancer resistance protein; BCRP) Exon 5 genotype is coded as 0/1/2 based on the number of G alleles.
Measured: At baseline
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
Cilengitide systemic exposure as measured by systemic clearance is used in this genotype-phenotype analysis. The ABCG2 (breast cancer resistance protein; BCRP) Exon 5 genotype is coded as 0/1/2 based on the number of G alleles.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2008 (estimated)
- Study startJun 2008
- Primary completionOct 2010
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Childhood High-grade Cerebellar AstrocytomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 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, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00679354
- Sponsor's protocol ID
- NCI-2009-00339
- Other IDs
- NCI-2009-00339, COG-ACNS0621, CDR0000595623, ACNS0621, ACNS0621, U10CA098543
- Status last verified
- Jul 2018
- First submitted
- 14 May 2008
- Last updated
- 1 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cilengitide (EMD 121974) (IND# 59073) in Recurrent or Progressive and Refractory Childhood High-Grade Glioma
- ClinicalTrials.gov ID
- NCT00679354
- Acronym / sponsor ID
- NCI-2009-00339
- Conditions
- Childhood High-grade Cerebellar Astrocytoma, Childhood High-grade Cerebral Astrocytoma, Recurrent Childhood Anaplastic Astrocytoma, Recurrent Childhood Anaplastic Oligoastrocytoma, Recurrent Childhood Anaplastic Oligodendroglioma, Recurrent Childhood Brain Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 16 May 2008 (estimated)
- Results
- Posted 20 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well cilengitide works in treating younger patients with recurrent or progressive high-grade glioma that has not responded to standard therapy. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES:
- To determine the objective response rate to cilengitide in younger patients with recurrent or progressive high-grade glioma that is refractory to standard therapy.
SECONDARY OBJECTIVES:
- To estimate the distribution of time to progression, time to treatment failure, and time to death in these patients.
II. To estimate the rate of toxicity, especially symptomatic intratumoral hemorrhage, in these patients.
III. To evaluate the pharmacokinetics of cilengitide in plasma using a limited sampling strategy.
IV. To evaluate the pharmacogenetic polymorphisms in drug transporters (eg, breast cancer resistance protein [BCRP], P-glycoprotein [P-gp]) and relate to cilengitide disposition.
OUTLINE:
Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then periodically for 3 years.
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 analysis, Other: pharmacological studyPatients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (56 listed)
- Histologically confirmed primary central nervous system (CNS) high-grade glioma, including any of the following:
- Recurrent or progressive disease that is refractory to standard therapy
- Radiographically documented measurable disease
- No diffuse pontine gliomas
- No evidence of prior CNS bleeding
Key exclusion criteria (0 listed)
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) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (cilengitide) |
Primary outcome
Objective Response to Cilengitide
Time frame: Up to 16 weeks
Objective response is defined as a complete response or partial response at 4 weeks that is sustained for at least another 4 weeks, or a stable disease at 4 weeks that is sustained for at least 12 weeks while on stable or decreasing dose of corticosteroids, except when corticosteroids are being used to control hydrocephaly unrelated to tumor progression.
12 secondary outcomes
Time to Tumor Progression (TTP)
Time frame: Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years
Time to Treatment Failure (TTF)
Time frame: Time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 5 years
Time to Death (TTD)
Time frame: Time from study enrollment to death from any cause, assessed up to 5 years
Rate of Toxicity, Especially That of Symptomatic Intratumoral Hemorrhage (ITH) Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Time frame: Up to 5 years
Pharmacokinetic Parameter of Cilengitide in Plasma: Volume of Central Compartment (Vc)
Time frame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacokinetic Parameter of Cilengitide in Plasma: Elimination Rate Constant (Ke)
Time frame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacokinetic Parameter of Cilengitide in Plasma: Half-life (t1/2)
Time frame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacokinetic Parameter of Cilengitide in Plasma: Systemic Clearance (Cl)
Time frame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by AUC
Time frame: At baseline
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
Time frame: At Baseline
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by AUC
Time frame: At baseline
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
Time frame: At baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Childhood High-grade Cerebellar Astrocytoma
Active, not recruitingPhase 4
Pediatric Long-Term Follow-up and Rollover Study
Diffuse Astrocytoma, Anaplastic Astrocytoma
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
Children's Oncology Group
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cilengitide, laboratory biomarker analysis and pharmacological study in people with Childhood High-grade Cerebellar Astrocytoma and Childhood High-grade Cerebral Astrocytoma, run by National Cancer Institute (NCI) at 20 sites in 2 countries.
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 56 inclusion and 0 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 1 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response to Cilengitide (time frame: Up to 16 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 1 Aug 2018.