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Trial record 38 of 55 for:    "Anaplastic oligoastrocytoma"

Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy

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ClinicalTrials.gov Identifier: NCT00679354
Recruitment Status : Completed
First Posted : May 16, 2008
Results First Posted : February 20, 2014
Last Update Posted : August 1, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
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
Recurrent Childhood Cerebellar Astrocytoma
Recurrent Childhood Cerebral Astrocytoma
Recurrent Childhood Glioblastoma
Recurrent Childhood Visual Pathway and Hypothalamic Glioma
Interventions Drug: cilengitide
Other: laboratory biomarker analysis
Other: pharmacological study
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Period Title: Overall Study
Started 30
Completed 0
Not Completed 30
Reason Not Completed
Death             3
Lack of Efficacy             22
Physician Decision             4
Ineligible             1
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 30 participants
13
(1 to 20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
14
  46.7%
Male
16
  53.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
1
   3.3%
Black or African American
6
  20.0%
White
20
  66.7%
More than one race
0
   0.0%
Unknown or Not Reported
3
  10.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
4
  13.3%
Not Hispanic or Latino
25
  83.3%
Unknown or Not Reported
1
   3.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 30 participants
United States 28
Canada 1
Australia 1
1.Primary Outcome
Title Objective Response to Cilengitide
Hide Description 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.
Time Frame Up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Six patients are considered inevaluable for objective response (including one ineligible patient) and excluded from analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
With Objective Response 1
Without Objective Response 23
2.Secondary Outcome
Title Time to Tumor Progression (TTP)
Hide Description The distribution of TTP will be analyzed separately using product limit (PL) estimate.
Time Frame Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
29 eligible patients are included in the analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Overall Number of Participants Analyzed 29
Median (Inter-Quartile Range)
Unit of Measure: Days
28
(25 to 41)
3.Secondary Outcome
Title Time to Treatment Failure (TTF)
Hide Description The distribution of TTF will be analyzed separately using PL estimate.
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
Hide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine eligible patients are included in the analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Overall Number of Participants Analyzed 29
Median (Inter-Quartile Range)
Unit of Measure: Days
28
(25 to 41)
4.Secondary Outcome
Title Time to Death (TTD)
Hide Description The distribution of TTD will be analyzed separately using PL estimate.
Time Frame Time from study enrollment to death from any cause, assessed up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine eligible patients are included in the analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Overall Number of Participants Analyzed 29
Median (Inter-Quartile Range)
Unit of Measure: Days
172
(99 to 226)
5.Secondary Outcome
Title Rate of Toxicity, Especially That of Symptomatic Intratumoral Hemorrhage (ITH) Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Hide Description Rate of individual toxicity including that of symptomatic ITH will be summarized in each course of treatment using standard descriptive statistical methods.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Twenty-nine eligible patients are included in the analysis. One patient was excluded due to ineligibility.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: percent of pts with symptomatic ITH
6.9
6.Secondary Outcome
Title Pharmacokinetic Parameter of Cilengitide in Plasma: Volume of Central Compartment (Vc)
Hide Description 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.
Time Frame At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Hide Outcome Measure Data
Hide Analysis Population Description
All 18 patients consenting for pharmacokinetic study are included in this analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: L/m^2
6.20
(3.34 to 10.72)
7.Secondary Outcome
Title Pharmacokinetic Parameter of Cilengitide in Plasma: Elimination Rate Constant (Ke)
Hide Description 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.
Time Frame At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Hide Outcome Measure Data
Hide Analysis Population Description
All 18 patients consenting for pharmacokinetic study are included in this analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: hr^(-1)
0.58
(0.36 to 1.00)
8.Secondary Outcome
Title Pharmacokinetic Parameter of Cilengitide in Plasma: Half-life (t1/2)
Hide Description 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.
Time Frame At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Hide Outcome Measure Data
Hide Analysis Population Description
All 18 patients consenting for pharmacokinetic study are included in this analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: hours
1.26
(0.69 to 1.90)
9.Secondary Outcome
Title Pharmacokinetic Parameter of Cilengitide in Plasma: Systemic Clearance (Cl)
Hide Description 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.
Time Frame At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Hide Outcome Measure Data
Hide Analysis Population Description
All 18 patients consenting for pharmacokinetic study are included in this analysis.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: L/hr/m^2
3.84
(2.47 to 5.75)
10.Secondary Outcome
Title Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by AUC
Hide Description 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.
Time Frame At baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes 12 eligible patients with both AUC data and ABCB1 Exon 26 data available.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: Spearman's correlation
0.00
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment (Cilengitide)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Spearman's Correlation
Comments [Not Specified]
Method of Estimation Estimation Parameter Spearman's Correlation Coefficient
Estimated Value 0.00
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
Hide Description 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.
Time Frame At Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes 12 eligible patients with both systemic clearance data and ABCB1 Exon 26 data available.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: Spearman's Correlation
0.56
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment (Cilengitide)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method Spearman's Correlation
Comments [Not Specified]
Method of Estimation Estimation Parameter Spearman's Correlation Coefficient
Estimated Value 0.56
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by AUC
Hide Description 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.
Time Frame At baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes 12 eligible patients with both AUC data and ABCG2 Exon 5 data available.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: Spearman’s Correlation
-0.22
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment (Cilengitide)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.495
Comments [Not Specified]
Method Spearman's Correlation
Comments [Not Specified]
Method of Estimation Estimation Parameter Spearman's Correlation Coefficient
Estimated Value -0.22
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
Hide Description 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.
Time Frame At baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes 12 eligible patients with both systemic clearance data and ABCG2 Exon 5 data available.
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description:
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: Spearman’s Correlation
-0.48
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment (Cilengitide)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.114
Comments [Not Specified]
Method Spearman's Correlation
Comments [Not Specified]
Method of Estimation Estimation Parameter Spearman's Correlation Coefficient
Estimated Value -0.48
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description Only eligible patients are included in the Toxicity reporting for both Serious and Other AEs. One patient was excluded from AE reporting because patient was deemed ineligible.
 
Arm/Group Title Treatment (Cilengitide)
Hide Arm/Group Description

Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.

cilengitide: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

All-Cause Mortality
Treatment (Cilengitide)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Cilengitide)
Affected / at Risk (%)
Total   8/29 (27.59%) 
Gastrointestinal disorders   
Vomiting  1/29 (3.45%) 
General disorders   
Death NOS  3/29 (10.34%) 
Fever  1/29 (3.45%) 
Musculoskeletal and connective tissue disorders   
Buttock pain  1/29 (3.45%) 
Nervous system disorders   
Cognitive disturbance  1/29 (3.45%) 
Encephalopathy  1/29 (3.45%) 
Headache  2/29 (6.90%) 
Intracranial hemorrhage  1/29 (3.45%) 
Seizure  2/29 (6.90%) 
Respiratory, thoracic and mediastinal disorders   
Apnea  1/29 (3.45%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Cilengitide)
Affected / at Risk (%)
Total   8/29 (27.59%) 
Gastrointestinal disorders   
Constipation  1/29 (3.45%) 
General disorders   
Fatigue  1/29 (3.45%) 
Immune system disorders   
Allergic reaction  1/29 (3.45%) 
Infections and infestations   
Upper respiratory infection  1/29 (3.45%) 
Investigations   
Lymphocyte count decreased  2/29 (6.90%) 
Neutrophil count decreased  1/29 (3.45%) 
White blood cell decreased  1/29 (3.45%) 
Metabolism and nutrition disorders   
Hypophosphatemia  1/29 (3.45%) 
Musculoskeletal and connective tissue disorders   
Muscle weakness left-sided  1/29 (3.45%) 
Nervous system disorders   
Depressed level of consciousness  1/29 (3.45%) 
Facial nerve disorder  1/29 (3.45%) 
Headache  2/29 (6.90%) 
Nervous system disorders - Other, specify  1/29 (3.45%) 
Peripheral sensory neuropathy  1/29 (3.45%) 
Renal and urinary disorders   
Urinary incontinence  1/29 (3.45%) 
Skin and subcutaneous tissue disorders   
Skin and subcutaneous tissue disorders - Other, specify  1/29 (3.45%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00679354     History of Changes
Obsolete Identifiers: NCT01648400
Other Study ID Numbers: NCI-2009-00339
NCI-2009-00339 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-ACNS0621
CDR0000595623
ACNS0621 ( Other Identifier: Children's Oncology Group )
ACNS0621 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: May 14, 2008
First Posted: May 16, 2008
Results First Submitted: January 6, 2014
Results First Posted: February 20, 2014
Last Update Posted: August 1, 2018