Trial Outcomes & Findings for Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy (NCT NCT00679354)

NCT ID: NCT00679354

Last Updated: 2018-08-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: Up to 16 weeks
• Results posted on: 2018-08-01

Participant Flow

Participant milestones

Measure	Treatment (Cilengitide) 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 Study STARTED	30
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	30

Reasons for withdrawal

Measure	Treatment (Cilengitide) 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 Study Death	3
Overall Study Lack of Efficacy	22
Overall Study Physician Decision	4
Overall Study Ineligible	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment (Cilengitide) n=30 Participants 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
Age, Continuous	13 years n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants
Region of Enrollment Canada	1 participants n=5 Participants
Region of Enrollment Australia	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 16 weeks

Population: Six patients are considered inevaluable for objective response (including one ineligible patient) and excluded from analysis.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=24 Participants 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
Objective Response to Cilengitide With Objective Response	1 participants
Objective Response to Cilengitide Without Objective Response	23 participants

SECONDARY outcome

Timeframe: Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years

Population: 29 eligible patients are included in the analysis.

The distribution of TTP will be analyzed separately using product limit (PL) estimate.

Outcome measures

Measure	Treatment (Cilengitide) n=29 Participants 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
Time to Tumor Progression (TTP)	28 Days Interval 25.0 to 41.0

SECONDARY outcome

Timeframe: 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

Population: Twenty-nine eligible patients are included in the analysis.

The distribution of TTF will be analyzed separately using PL estimate.

Outcome measures

Measure	Treatment (Cilengitide) n=29 Participants 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
Time to Treatment Failure (TTF)	28 Days Interval 25.0 to 41.0

SECONDARY outcome

Timeframe: Time from study enrollment to death from any cause, assessed up to 5 years

Population: Twenty-nine eligible patients are included in the analysis.

The distribution of TTD will be analyzed separately using PL estimate.

Outcome measures

Measure	Treatment (Cilengitide) n=29 Participants 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
Time to Death (TTD)	172 Days Interval 99.0 to 226.0

SECONDARY outcome

Timeframe: Up to 5 years

Population: Twenty-nine eligible patients are included in the analysis. One patient was excluded due to ineligibility.

Rate of individual toxicity including that of symptomatic ITH will be summarized in each course of treatment using standard descriptive statistical methods.

Outcome measures

Measure	Treatment (Cilengitide) n=29 Participants 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
Rate of Toxicity, Especially That of Symptomatic Intratumoral Hemorrhage (ITH) Assessed by Common Terminology Criteria for Adverse Events Version 4.0	6.9 percent of pts with symptomatic ITH

SECONDARY outcome

Timeframe: At baseline and 1, 3, and 6 hours after the first dose of cilengitide

Population: All 18 patients consenting for pharmacokinetic study are included in this analysis.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=18 Participants 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
Pharmacokinetic Parameter of Cilengitide in Plasma: Volume of Central Compartment (Vc)	6.20 L/m^2 Interval 3.34 to 10.72

SECONDARY outcome

Timeframe: At baseline and 1, 3, and 6 hours after the first dose of cilengitide

Population: All 18 patients consenting for pharmacokinetic study are included in this analysis.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=18 Participants 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
Pharmacokinetic Parameter of Cilengitide in Plasma: Elimination Rate Constant (Ke)	0.58 hr^(-1) Interval 0.36 to 1.0

SECONDARY outcome

Timeframe: At baseline and 1, 3, and 6 hours after the first dose of cilengitide

Population: All 18 patients consenting for pharmacokinetic study are included in this analysis.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=18 Participants 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
Pharmacokinetic Parameter of Cilengitide in Plasma: Half-life (t1/2)	1.26 hours Interval 0.69 to 1.9

SECONDARY outcome

Timeframe: At baseline and 1, 3, and 6 hours after the first dose of cilengitide

Population: All 18 patients consenting for pharmacokinetic study are included in this analysis.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=18 Participants 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
Pharmacokinetic Parameter of Cilengitide in Plasma: Systemic Clearance (Cl)	3.84 L/hr/m^2 Interval 2.47 to 5.75

SECONDARY outcome

Timeframe: At baseline

Population: The analysis includes 12 eligible patients with both AUC data and ABCB1 Exon 26 data available.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=12 Participants 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
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by AUC	0.00 Spearman's correlation

SECONDARY outcome

Timeframe: At Baseline

Population: The analysis includes 12 eligible patients with both systemic clearance data and ABCB1 Exon 26 data available.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=12 Participants 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
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by Systemic Clearance	0.56 Spearman's Correlation

SECONDARY outcome

Timeframe: At baseline

Population: The analysis includes 12 eligible patients with both AUC data and ABCG2 Exon 5 data available.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=12 Participants 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
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by AUC	-0.22 Spearman's Correlation

SECONDARY outcome

Timeframe: At baseline

Population: The analysis includes 12 eligible patients with both systemic clearance data and ABCG2 Exon 5 data available.

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.

Outcome measures

Measure	Treatment (Cilengitide) n=12 Participants 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
Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by Systemic Clearance	-0.48 Spearman's Correlation

Adverse Events

Treatment (Cilengitide)

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment (Cilengitide) n=29 participants at risk 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
Respiratory, thoracic and mediastinal disorders Apnea	3.4% 1/29 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.
Musculoskeletal and connective tissue disorders Buttock pain	3.4% 1/29 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.
Nervous system disorders Cognitive disturbance	3.4% 1/29 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.
General disorders Death NOS	10.3% 3/29 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.
Nervous system disorders Encephalopathy	3.4% 1/29 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.
General disorders Fever	3.4% 1/29 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.
Nervous system disorders Headache	6.9% 2/29 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.
Nervous system disorders Intracranial hemorrhage	3.4% 1/29 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.
Nervous system disorders Seizure	6.9% 2/29 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.
Gastrointestinal disorders Vomiting	3.4% 1/29 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.

Other adverse events

Measure	Treatment (Cilengitide) n=29 participants at risk 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
Immune system disorders Allergic reaction	3.4% 1/29 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.
Gastrointestinal disorders Constipation	3.4% 1/29 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.
Nervous system disorders Depressed level of consciousness	3.4% 1/29 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.
Nervous system disorders Facial nerve disorder	3.4% 1/29 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.
General disorders Fatigue	3.4% 1/29 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.
Nervous system disorders Headache	6.9% 2/29 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.
Metabolism and nutrition disorders Hypophosphatemia	3.4% 1/29 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.
Investigations Lymphocyte count decreased	6.9% 2/29 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.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	3.4% 1/29 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.
Nervous system disorders Nervous system disorders - Other, specify	3.4% 1/29 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.
Investigations Neutrophil count decreased	3.4% 1/29 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.
Nervous system disorders Peripheral sensory neuropathy	3.4% 1/29 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.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	3.4% 1/29 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.
Infections and infestations Upper respiratory infection	3.4% 1/29 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.
Renal and urinary disorders Urinary incontinence	3.4% 1/29 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.
Investigations White blood cell decreased	3.4% 1/29 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.

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: resultsreportingcoordinator@childrensoncologygroup.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60