Trial Outcomes & Findings for Cilengitide in Treating Patients Who Are Undergoing Surgery for Recurrent or Progressive Glioblastoma Multiforme (NCT NCT00112866)
NCT ID: NCT00112866
Last Updated: 2017-06-14
Results Overview
progression within 6 months (26 weeks) of treatment
TERMINATED
PHASE2
30 participants
6 months
2017-06-14
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 milestones
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
|
Overall Study
COMPLETED
|
13
|
13
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
did not start treatment post-op
|
1
|
2
|
Baseline Characteristics
Cilengitide in Treating Patients Who Are Undergoing Surgery for Recurrent or Progressive Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
Low Dose 500mg Group 1
n=15 Participants
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
|
High Dose 2000mg Group 2
n=15 Participants
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
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51 years
n=99 Participants
|
56 years
n=107 Participants
|
55 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
15 participants
n=99 Participants
|
14 participants
n=107 Participants
|
29 participants
n=206 Participants
|
|
Histology - Glioblastoma
|
15 participants
n=99 Participants
|
15 participants
n=107 Participants
|
30 participants
n=206 Participants
|
|
Prior Chemotherapy
|
15 participants
n=99 Participants
|
15 participants
n=107 Participants
|
30 participants
n=206 Participants
|
|
Prior Immunotherapy
Yes
|
1 participants
n=99 Participants
|
2 participants
n=107 Participants
|
3 participants
n=206 Participants
|
|
Prior Immunotherapy
No
|
14 participants
n=99 Participants
|
13 participants
n=107 Participants
|
27 participants
n=206 Participants
|
|
Prior Radiotherapy
|
15 participants
n=99 Participants
|
15 participants
n=107 Participants
|
30 participants
n=206 Participants
|
|
Prior Biopsy Only
yes
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Prior Biopsy Only
no
|
14 participants
n=99 Participants
|
15 participants
n=107 Participants
|
29 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: 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.
progression within 6 months (26 weeks) of treatment
Outcome measures
| Measure |
Post-Operative Treatment 2000mg
n=26 Participants
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
|
Group II Pre-op (High-dose Cilengitide) 2000mg
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
|
|---|---|---|
|
6m-Progression-free Survival
|
12 percent
|
—
|
SECONDARY outcome
Timeframe: Baseline and time of surgeryPopulation: 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
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and time of surgeryPopulation: 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
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and time of surgeryPopulation: 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
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and time of surgeryPopulation: 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
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and up to 4 yearsPopulation: 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
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 hour post concentrationPopulation: 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.
24 hour post dose concentration plasma, at time of resection
Outcome measures
| Measure |
Post-Operative Treatment 2000mg
n=8 Participants
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
|
Group II Pre-op (High-dose Cilengitide) 2000mg
n=11 Participants
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
|
|---|---|---|
|
Plasma Concentration of EMD 121974
|
333 ng/ml
Standard Deviation 16.97
|
386 ng/ml
Standard Deviation 184
|
SECONDARY outcome
Timeframe: at time of surgeryPopulation: 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
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.
Outcome measures
| Measure |
Post-Operative Treatment 2000mg
n=7 Participants
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
|
Group II Pre-op (High-dose Cilengitide) 2000mg
n=5 Participants
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
|
|---|---|---|
|
Tumor Tissue Concentrations
|
919 ng/g
Standard Deviation 1235
|
1413 ng/g
Standard Deviation 1335
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 yearPopulation: 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.
Kaplan-meier curve
Outcome measures
| Measure |
Post-Operative Treatment 2000mg
n=26 Participants
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
|
Group II Pre-op (High-dose Cilengitide) 2000mg
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 Progression Free Survival
|
8 weeks
Interval 4.0 to 16.0
|
—
|
Adverse Events
Post-Operative 2000mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Post-Operative 2000mg
n=26 participants at risk
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
|
|---|---|
|
Investigations
Alanine aminotransferase
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
Metabolism and nutrition disorders
anorexia
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
Injury, poisoning and procedural complications
bruising
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
Gastrointestinal disorders
diarrhea
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
General disorders
fatigue
|
30.8%
8/26 • Number of events 8 • 1 year
|
|
Investigations
hemoglobin
|
30.8%
8/26 • Number of events 8 • 1 year
|
|
Metabolism and nutrition disorders
hyperglycemia
|
11.5%
3/26 • Number of events 3 • 1 year
|
|
Metabolism and nutrition disorders
hyponatremia
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
Metabolism and nutrition disorders
hypoalbuminemia
|
11.5%
3/26 • Number of events 3 • 1 year
|
|
Blood and lymphatic system disorders
leukocytes
|
38.5%
10/26 • Number of events 10 • 1 year
|
|
Blood and lymphatic system disorders
lymphopenia
|
42.3%
11/26 • Number of events 11 • 1 year
|
|
Gastrointestinal disorders
nausea
|
11.5%
3/26 • Number of events 3 • 1 year
|
|
Investigations
neutrophils
|
11.5%
3/26 • Number of events 3 • 1 year
|
|
Investigations
platelets
|
23.1%
6/26 • Number of events 6 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60