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| ID | Type | Description | Link |
|---|---|---|---|
| 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 | View source |
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due to poor accrual
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Cilengitide may stop the growth of glioblastoma multiforme by blocking blood flow to the tumor. Giving cilengitide before and after surgery may be an effective treatment for glioblastoma multiforme. This phase II trial is studying how well cilengitide works in treating patients who are undergoing surgery for recurrent or progressive glioblastoma multiforme.
PRIMARY OBJECTIVES:
I. Determine the 6-month progression-free survival rate in operative patients with recurrent or progressive glioblastoma multiforme treated with cilengitide.
SECONDARY OBJECTIVES:
I. Determine the safety and toxicity of this drug in these patients.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment groups for the preoperative treatment component.
Preoperative Treatment Group I: Patients receive high-dose cilengitide IV over 1 hour on days -8, -4, and -1.
Preoperative Treatment Group II: Patients receive low-dose 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 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.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 44 patients (22 per preoperative treatment group) will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group I (high-dose cilengitide) 2000mg | Experimental | Preoperative Treatment: Patients receive high-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 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. |
|
| Group II (low-dose cilengitide) 500mg | Experimental | Preoperative Treatment: Patients receive low-dose cilengitide IV over 1 hour on days -8, -4, and -1. (500mg) Resection: All patients undergo tumor resection on day 0. 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cilengitide | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| 6m-Progression-free Survival | progression within 6 months (26 weeks) of treatment | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in avb3 Integrin Expression on Tumor Cells and Endothelial Cells | 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. | Baseline and time of surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Progression Free Survival | Kaplan-meier curve | 1 year |
Inclusion Criteria:
Histologically confirmed intracranial glioblastoma multiforme (GBM)
Original diagnosis of low-grade glioma with subsequent histological confirmation of GBM allowed
Recurrent disease
Must require a surgical procedure (gross total or near gross total resection) for tumor removal
Performance status - Karnofsky 60-100%
White Blood Count (WBC) ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL (transfusion allowed)
Serum glutamic oxaloacetic transaminase (SGOT) < 2 times upper limit of normal (ULN)
Bilirubin < 2 times ULN
Creatinine < 1.5 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for ≥ 2 weeks after study participation (for female patients) or for 3 months after study participation (for male patients)
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
No active infection
No other significant uncontrolled medical illness that would preclude study participation
At least 3 weeks since prior interferon
No prior cilengitide
No other prior targeted antiangiogenic treatment (e.g., vatalanib, SU5416, or thalidomide)
No concurrent anticancer immunotherapy
No concurrent routine prophylactic filgrastim (G-CSF)
At least 2 weeks since prior vincristine
At least 3 weeks since prior procarbazine
At least 6 weeks since prior nitrosoureas
No concurrent anticancer chemotherapy
At least 3 weeks since prior tamoxifen
No concurrent anticancer hormonal therapy
See Disease Characteristics
At least 4 weeks since prior radiotherapy
No concurrent anticancer radiotherapy
Recovered from all prior therapies
No more than 3 prior treatments for GBM (1 initial treatment; and treatment for 2 relapses)
At least 4 weeks since prior investigational agents
At least 4 weeks since prior cytotoxic therapy
At least 3 weeks since other prior non-cytotoxic therapy (e.g., isotretinoin), except radiosensitizers
No other concurrent anticancer therapy
No other concurrent investigational agents
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| Name | Affiliation | Role |
|---|---|---|
| Mark Gilbert | North American Brain Tumor Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| North American Brain Tumor Consortium | Watertown | Massachusetts | 02472 | United States |
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Patients were enrolled from March 2005 through October 2006. Patients were recruited in the outpatient setting, however patients did need surgery for this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose 500mg Group 1 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| therapeutic conventional surgery | Procedure | Undergo tumor resection |
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| pharmacological study | Other | Correlative studies |
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| laboratory biomarker analysis | Other | Correlative studies |
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| Changes in Vitronectin Expression | 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. | Baseline and time of surgery |
| Changes in Tumor Cell Apoptosis | 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. | Baseline and time of surgery |
| Changes in Tumor Cell Proliferation | 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. | Baseline and time of surgery |
| Changes in Endothelial Cell Apoptosis | 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. | Baseline and up to 4 years |
| Plasma Concentration of EMD 121974 | 24 hour post dose concentration plasma, at time of resection | 24 hour post concentration |
| Tumor Tissue Concentrations | 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. | at time of surgery |
| FG001 | High Dose 2000mg Group 2 | 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 |
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| NOT COMPLETED |
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26 patients evaluated for toxicity and efficacy. 1 patient deemed ineligible and 3 patients did not re-start treatment post surgery.
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| ID | Title | Description |
|---|---|---|
| BG000 | Low Dose 500mg Group 1 | 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 |
| BG001 | High Dose 2000mg Group 2 | 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Histology - Glioblastoma | Number | participants |
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| Prior Chemotherapy | Number | participants |
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| Prior Immunotherapy | Number | participants |
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| Prior Radiotherapy | Number | participants |
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| Prior Biopsy Only | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 6m-Progression-free Survival | progression within 6 months (26 weeks) of treatment | 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. | Posted | Number | percent | 6 months |
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| Secondary | Changes in avb3 Integrin Expression on Tumor Cells and Endothelial Cells | 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. | 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 | Posted | Baseline and time of surgery |
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| Secondary | Changes in Vitronectin Expression | 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. | 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 | Posted | Baseline and time of surgery |
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| Secondary | Changes in Tumor Cell Apoptosis | 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. | 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 | Posted | Baseline and time of surgery |
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| Secondary | Changes in Tumor Cell Proliferation | 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. | 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 | Posted | Baseline and time of surgery |
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| Secondary | Changes in Endothelial Cell Apoptosis | 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. | 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 | Posted | Baseline and up to 4 years |
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| Secondary | Plasma Concentration of EMD 121974 | 24 hour post dose concentration plasma, at time of resection | 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. | Posted | Mean | Standard Deviation | ng/ml | 24 hour post concentration |
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| Secondary | Tumor Tissue Concentrations | 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. | 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 | Posted | Mean | Standard Deviation | ng/g | at time of surgery |
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| Other Pre-specified | Overall Progression Free Survival | Kaplan-meier curve | 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. | Posted | Median | 95% Confidence Interval | weeks | 1 year |
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1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Post-Operative 2000mg | 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 | 0 | 26 | 26 | 26 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase | Investigations | CTCAE (3.0) | Non-systematic Assessment |
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| anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
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| bruising | Injury, poisoning and procedural complications | CTCAE (3.0) | Non-systematic Assessment |
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| diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| fatigue | General disorders | CTCAE (3.0) | Non-systematic Assessment |
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| hemoglobin | Investigations | CTCAE (3.0) | Non-systematic Assessment |
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| hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
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| hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
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| hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
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| leukocytes | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
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| lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
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| nausea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
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| neutrophils | Investigations | CTCAE (3.0) | Non-systematic Assessment |
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| platelets | Investigations | CTCAE (3.0) | Non-systematic Assessment |
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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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Gilbert, MD | Adult Brain Tumor Consortium (ABTC) | 410-955-8837 | jfisher@jhmi.edu |
| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C422910 | Cilengitide |
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| White |
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