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Cilengitide in Treating Patients Who Are Undergoing Surgery for Recurrent or Progressive Glioblastoma Multiforme

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ClinicalTrials.gov Identifier: NCT00112866
Recruitment Status : Terminated (due to poor accrual)
First Posted : June 3, 2005
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Interventions Drug: cilengitide
Procedure: therapeutic conventional surgery
Other: pharmacological study
Other: laboratory biomarker analysis
Enrollment 30
Recruitment Details Patients were enrolled from March 2005 through October 2006. Patients were recruited in the outpatient setting, however patients did need surgery for this study.
Pre-assignment Details  
Arm/Group Title Low Dose 500mg Group 1 High Dose 2000mg Group 2
Hide Arm/Group Description

Preoperative Treatment: Patients receive low dose cilengitide 500mg IV over 1 hour on days -8, -4, and -1.

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose cilengitide 2000mg IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive high-dose cilengitide 2000mg IV over 1 hour on days -8, -4, and -1.

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Period Title: Overall Study
Started 15 15
Completed 13 13
Not Completed 2 2
Reason Not Completed
Protocol Violation             1             0
did not start treatment post-op             1             2
Arm/Group Title Low Dose 500mg Group 1 High Dose 2000mg Group 2 Total
Hide Arm/Group Description

Preoperative Treatment: Patients receive low dose 500mg cilengitide IV over 1 hour on days -8, -4, and -1.

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive high-dose 2000mg cilengitide IV over 1 hour on days -8, -4, and -1.

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Total of all reporting groups
Overall Number of Baseline Participants 15 15 30
Hide Baseline Analysis Population Description
26 patients evaluated for toxicity and efficacy. 1 patient deemed ineligible and 3 patients did not re-start treatment post surgery.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 15 participants 15 participants 30 participants
51
(42 to 63)
56
(42 to 68)
55
(42 to 68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
Female
10
  66.7%
8
  53.3%
18
  60.0%
Male
5
  33.3%
7
  46.7%
12
  40.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
Asian 0 1 1
White 15 14 29
Histology - Glioblastoma  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
15 15 30
Prior Chemotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
15 15 30
Prior Immunotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
Yes 1 2 3
No 14 13 27
Prior Radiotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
15 15 30
Prior Biopsy Only  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 30 participants
yes 1 0 1
no 14 15 29
1.Primary Outcome
Title 6m-Progression-free Survival
Hide Description progression within 6 months (26 weeks) of treatment
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
6months progression free survival based on the post surgical treatment. All patients received 2000mg post surgery. The pre-surgery dose was used for correlative purposes only. All patients received surgery and the doses pre-surgery have no relation to the primary objective.
Arm/Group Title Post-Operative Treatment 2000mg
Hide Arm/Group Description:

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

pharmacological study: Correlative studies

Overall Number of Participants Analyzed 26
Measure Type: Number
Unit of Measure: percent
12
2.Secondary Outcome
Title Changes in avb3 Integrin Expression on Tumor Cells and Endothelial Cells
Hide Description Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Time Frame Baseline and time of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Molecular analyses evaluating alterations after cilengitide treatments were planned as a component of this clinical trial, unfortunately, the majority of tumor samples were too small to do both measures of drug and molecular analysis or the sample was inadequate for both after removal of areas of necrosis and gliosis
Arm/Group Title Group I Pre-op (Low-dose Cilengitide) 500mg Group II Pre-op (High-dose Cilengitide) 2000mg
Hide Arm/Group Description:

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (low dose 500mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1. (2000mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Changes in Vitronectin Expression
Hide Description Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Time Frame Baseline and time of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Molecular analyses evaluating alterations planned, unfortunately, majority of tumor samples were too small to do both measures of drug and molecular analysis or sample was inadequate for both after removal of areas of necrosis and gliosis
Arm/Group Title Group I Pre-op (Low-dose Cilengitide) 500mg Group II Pre-op (High-dose Cilengitide) 2000mg
Hide Arm/Group Description:

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (low dose 500mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1. (2000mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Changes in Tumor Cell Apoptosis
Hide Description Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Time Frame Baseline and time of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Molecular analyses evaluating alterations planned, unfortunately, majority of tumor samples were too small to do both measures of drug and molecular analysis or sample was inadequate for both after removal of areas of necrosis and gliosis
Arm/Group Title Group I Pre-op (Low-dose Cilengitide) 500mg Group II Pre-op (High-dose Cilengitide) 2000mg
Hide Arm/Group Description:

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (low dose 500mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (low dose 500mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Changes in Tumor Cell Proliferation
Hide Description Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Time Frame Baseline and time of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
Molecular analyses evaluating alterations planned, unfortunately, majority of tumor samples were too small to do both measures of drug and molecular analysis or sample was inadequate for both after removal of areas of necrosis and gliosis
Arm/Group Title Group I Pre-op (Low-dose Cilengitide) 500mg Group II Pre-op (High-dose Cilengitide) 2000mg
Hide Arm/Group Description:

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (low dose 500mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1. (2000mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Changes in Endothelial Cell Apoptosis
Hide Description Will be performed between the untreated matched control tumor tissue and the tissue obtained from the post-treatment tumors using either a Fisher's Exact test or the Wilcoxon rank sum test depending on whether the assay provides a measurement or is yes/no.
Time Frame Baseline and up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Molecular analyses evaluating alterations planned, unfortunately, majority of tumor samples were too small to do both measures of drug and molecular analysis or sample was inadequate for both after removal of areas of necrosis and gliosis
Arm/Group Title Group II Pre-op (High-dose Cilengitide) 2000mg Group I Pre-op (Low-dose Cilengitide) 500mg
Hide Arm/Group Description:

Preoperative Treatment: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1. (2000mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (low dose 500mg)

Resection: All patients undergo tumor resection on day 0.

cilengitide: Given IV therapeutic conventional surgery: Undergo tumor resection

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Plasma Concentration of EMD 121974
Hide Description 24 hour post dose concentration plasma, at time of resection
Time Frame 24 hour post concentration
Hide Outcome Measure Data
Hide Analysis Population Description
6 of 8 and 7 of 11 plasma samples at the 500mg and 2000mg dose level respectively, were below the lower level of quantitation (LLOQ) Of the 15 samples in the low dose group only 8 were evaluable and 11 of the 15 for the high dose group. Samples were either damaged or too small for analysis.
Arm/Group Title Group I (Low-dose Cilengitide) 500mg Group II High-dose Cilengitide) 2000mg
Hide Arm/Group Description:

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (High dose 2000mg)

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive 2000mg high-dose cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1. (2000mg)

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 8 11
Mean (Standard Deviation)
Unit of Measure: ng/ml
333  (16.97) 386  (184)
8.Secondary Outcome
Title Tumor Tissue Concentrations
Hide Description a section of tumor of approximately 500mg will be snap frozen (immediately prepared and frozen) once removed from brain for analysis of the drug concentration in contrast -enhancing tumor.
Time Frame at time of surgery
Hide Outcome Measure Data
Hide Analysis Population Description
8 500mg dose tissue samples and 10 2000mg dose tissue samples were either too small or had large areas of necrosis and gliosis to do analysis/evaluation
Arm/Group Title Group I (Low-dose Cilengitide) 500mg Group II (High-dose Cilengitide) 2000mg
Hide Arm/Group Description:

Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (low dose 500mg)

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Preoperative Treatment: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1. (2000mg)

Resection: All patients undergo tumor resection on day 0.

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 7 5
Mean (Standard Deviation)
Unit of Measure: ng/g
919  (1235) 1413  (1335)
9.Other Pre-specified Outcome
Title Overall Progression Free Survival
Hide Description Kaplan-meier curve
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Overall survival based on the post surgical treatment. All patients received 2000mg post surgery. The pre-surgery dose was used for correlative purposes only. All patients received surgery and the doses pre-surgery have no relation to the this objective.
Arm/Group Title Post-Operative Treatment 2000mg
Hide Arm/Group Description:

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 26
Median (95% Confidence Interval)
Unit of Measure: weeks
8
(4 to 16)
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Post-Operative 2000mg
Hide Arm/Group Description

Postoperative Treatment: Beginning within 2 weeks after surgery, all patients receive high-dose 2000mg cilengitide IV over 1 hour twice weekly for 4 weeks. Treatment repeats every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

cilengitide: Given IV

therapeutic conventional surgery: Undergo tumor resection

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

All-Cause Mortality
Post-Operative 2000mg
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Post-Operative 2000mg
Affected / at Risk (%) # Events
Total   0/26 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Post-Operative 2000mg
Affected / at Risk (%) # Events
Total   26/26 (100.00%)    
Blood and lymphatic system disorders   
leukocytes * 1  10/26 (38.46%)  10
lymphopenia * 1  11/26 (42.31%)  11
Gastrointestinal disorders   
diarrhea * 1  2/26 (7.69%)  2
nausea * 1  3/26 (11.54%)  3
General disorders   
fatigue * 1  8/26 (30.77%)  8
Injury, poisoning and procedural complications   
bruising * 1  2/26 (7.69%)  2
Investigations   
Alanine aminotransferase * 1  2/26 (7.69%)  2
hemoglobin * 1  8/26 (30.77%)  8
neutrophils * 1  3/26 (11.54%)  3
platelets * 1  6/26 (23.08%)  6
Metabolism and nutrition disorders   
anorexia * 1  2/26 (7.69%)  2
hyperglycemia * 1  3/26 (11.54%)  3
hyponatremia * 1  2/26 (7.69%)  2
hypoalbuminemia * 1  3/26 (11.54%)  3
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Study closed early due to slow accrual. Molecular analyses evaluating alterations were planned for the study, unfortunately, majority of tumor samples were too small to do analysis and also there were unforeseen freezer issues.
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
Layout table for Results Point of Contact information
Name/Title: Mark Gilbert, MD
Organization: Adult Brain Tumor Consortium (ABTC)
Phone: 410-955-8837
EMail: jfisher@jhmi.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112866    
Other Study ID Numbers: NCI-2012-02653
NCI-2012-02653 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000428409
NABTC-03-02 ( Other Identifier: North American Brain Tumor Consortium )
NABTC-03-02 ( Other Identifier: CTEP )
U01CA062399 ( U.S. NIH Grant/Contract )
First Submitted: June 2, 2005
First Posted: June 3, 2005
Results First Submitted: October 7, 2016
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017