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TerminatedNCT00112866Updated Jun 14, 2017Results posted

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

A Phase 2 interventional study of cilengitide and therapeutic conventional surgery in Adult Giant Cell Glioblastoma, Adult Glioblastoma and Adult Gliosarcoma, sponsored by National Cancer Institute (NCI). Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-06-14.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Why this study was terminated
due to poor accrual
Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
03

In context

Glioblastoma

1,920 studies on the registry are indexed under Glioblastoma; 449 are open to participants now.

This study's enrollment of 30 is below the median of 36 across 1,617 interventional studies indexed under Glioblastoma.

Browse Glioblastoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  • Histologically confirmed intracranial glioblastoma multiforme (GBM)

    • Original diagnosis of low-grade glioma with subsequent histological confirmation of GBM allowed

    • Recurrent disease

      • Failed prior radiotherapy
  • 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)

    • For patients who received prior therapy for low-grade glioma, a subsequent surgical diagnosis of high-grade glioma is considered the first relapse
  • 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Group I (high-dose cilengitide) 2000mg

    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.

    Drug: cilengitide · Procedure: therapeutic conventional surgery · Other: pharmacological study · Other: laboratory biomarker analysis

  • Experimental
    Group II (low-dose cilengitide) 500mg

    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

    Drug: cilengitide · Procedure: therapeutic conventional surgery · Other: pharmacological study · Other: laboratory biomarker analysis

Interventions

  • Drugcilengitide

    Given IV

    Also known as: EMD 121974

  • Proceduretherapeutic conventional surgery

    Undergo tumor resection

  • Otherpharmacological study

    Correlative studies

    Also known as: pharmacological studies

  • Otherlaboratory biomarker analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. 6m-Progression-free Survival

    progression within 6 months (26 weeks) of treatment

    Time frame: 6 months

Secondary outcomes

  1. 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.

    Time frame: Baseline and time of surgery

  2. 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.

    Time frame: Baseline and time of surgery

  3. 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.

    Time frame: Baseline and time of surgery

  4. 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.

    Time frame: Baseline and time of surgery

  5. 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.

    Time frame: Baseline and up to 4 years

  6. Plasma Concentration of EMD 121974

    24 hour post dose concentration plasma, at time of resection

    Time frame: 24 hour post concentration

  7. 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.

    Time frame: at time of surgery

Other outcomes

  1. Overall Progression Free Survival

    Kaplan-meier curve

    Time frame: 1 year

07

Results

Posted Jun 14, 2017
Limitations and caveats
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.

Participant flow

Patients were enrolled from March 2005 through October 2006. Patients were recruited in the outpatient setting, however patients did need surgery for this study.

Participant flow — Overall Study
MilestoneLow Dose 500mg Group 1High Dose 2000mg Group 2
Started1515
Completed1313
Not completed22
Withdrew: Protocol violation10
Withdrew: Did not start treatment post-op12

Outcome measures

Primary6m-Progression-free Survival

progression within 6 months (26 weeks) of treatment

Time frame:
6 months
Reported as:
Number · percent
6m-Progression-free Survival
percentPost-Operative Treatment 2000mg
6m-Progression-free Survival12
SecondaryChanges 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.

Time frame:
Baseline and time of surgery

No measurements were reported for this outcome.

SecondaryChanges 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.

Time frame:
Baseline and time of surgery

No measurements were reported for this outcome.

SecondaryChanges 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.

Time frame:
Baseline and time of surgery

No measurements were reported for this outcome.

SecondaryChanges 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.

Time frame:
Baseline and time of surgery

No measurements were reported for this outcome.

SecondaryChanges 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.

Time frame:
Baseline and up to 4 years

No measurements were reported for this outcome.

SecondaryPlasma Concentration of EMD 121974

24 hour post dose concentration plasma, at time of resection

Time frame:
24 hour post concentration
Reported as:
Mean · ng/ml
Plasma Concentration of EMD 121974
ng/mlGroup I (Low-dose Cilengitide) 500mgGroup II High-dose Cilengitide) 2000mg
Plasma Concentration of EMD 121974333 ± 16.97386 ± 184
SecondaryTumor 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.

Time frame:
at time of surgery
Reported as:
Mean · ng/g
Tumor Tissue Concentrations
ng/gGroup I (Low-dose Cilengitide) 500mgGroup II (High-dose Cilengitide) 2000mg
Tumor Tissue Concentrations919 ± 12351413 ± 1335
Other pre-specifiedOverall Progression Free Survival

Kaplan-meier curve

Time frame:
1 year
Reported as:
Median · weeks
Overall Progression Free Survival
weeksPost-Operative Treatment 2000mg
Overall Progression Free Survival8 (4 to 16)

Adverse events

Collected over 1 year. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Post-Operative 2000mg—0/26 (0%)26/26 (100%)
Most frequent other events
Showing 10 of 14
Most frequent other events
EventPost-Operative 2000mg
lymphopeniaBlood and lymphatic system disorders11/26
leukocytesBlood and lymphatic system disorders10/26
fatigueGeneral disorders8/26
hemoglobinInvestigations8/26
plateletsInvestigations6/26
hyperglycemiaMetabolism and nutrition disorders3/26
hypoalbuminemiaMetabolism and nutrition disorders3/26
nauseaGastrointestinal disorders3/26
neutrophilsInvestigations3/26
Alanine aminotransferaseInvestigations2/26

Baseline characteristics

26 patients evaluated for toxicity and efficacy. 1 patient deemed ineligible and 3 patients did not re-start treatment post surgery.

Age, Continuous
Age, Continuous(years)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
Median51 (42 to 63)56 (42 to 68)55 (42 to 68)
Sex: Female, Male
Sex: Female, Male(Participants)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
Female10818
Male5712
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
Asian011
White151429
Histology - Glioblastoma
Histology - Glioblastoma(participants)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
Number151530
Prior Chemotherapy
Prior Chemotherapy(participants)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
Number151530
Prior Immunotherapy
Prior Immunotherapy(participants)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
Yes123
No141327
Prior Radiotherapy
Prior Radiotherapy(participants)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
Number151530
Prior Biopsy Only
Prior Biopsy Only(participants)Low Dose 500mg Group 1High Dose 2000mg Group 2Total
yes101
no141529
08

Study locations

1 site
  • North American Brain Tumor Consortium
    Watertown, Massachusetts 02472, United States
09

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 14, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00112866
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 3, 2005
Start date
Jan 2005
Primary completion
Dec 2008
Completion
Mar 2009
Results posted
Jun 14, 2017
Last update
Jun 14, 2017

Study contacts

Mark Gilbert
principal investigator · North American Brain Tumor Consortium

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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