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

Recurrent Childhood Cerebellar Astrocytoma Clinical Trial

Official title:

Cilengitide (EMD 121974) (IND# 59073) in Recurrent or Progressive and Refractory Childhood High-Grade Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00679354
• Other study ID #: NCI-2009-00339
• Secondary ID: NCI-2009-00339CO
• Status: Completed
• Phase: Phase 2
• Start date: June 2008
• Est. completion date: July 2011

Study information

• Verified date: July 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well cilengitide works in treating younger patients with recurrent or progressive high-grade glioma that has not responded to standard therapy. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor.

Description:

PRIMARY OBJECTIVES:

I. To determine the objective response rate to cilengitide in younger patients with recurrent or progressive high-grade glioma that is refractory to standard therapy.

SECONDARY OBJECTIVES:

I. To estimate the distribution of time to progression, time to treatment failure, and time to death in these patients.

II. To estimate the rate of toxicity, especially symptomatic intratumoral hemorrhage, in these patients.

III. To evaluate the pharmacokinetics of cilengitide in plasma using a limited sampling strategy.

IV. To evaluate the pharmacogenetic polymorphisms in drug transporters (eg, breast cancer resistance protein [BCRP], P-glycoprotein [P-gp]) and relate to cilengitide disposition.

OUTLINE:

Patients receive cilengitide IV over 1 hour 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.

After completion of study treatment, patients are followed up every 3 months for 2 years and then periodically for 3 years.

Other known NCT identifiers

• NCT01648400

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed primary central nervous system (CNS) high-grade glioma, including any of the following:

• Glioblastoma multiforme

• Anaplastic astrocytoma

• Anaplastic oligodendroglioma

• High-grade astrocytoma not otherwise specified (i.e., anaplastic ganglioglioma, anaplastic mixed glioma, or anaplastic mixed glioneuronal tumors)

• No diffuse pontine gliomas, gliomatosis cerebri, and primary spinal cord high-grade astrocytoma

• Gliosarcoma

• Recurrent or progressive disease that is refractory to standard therapy

• Radiographically documented measurable disease

• Lesion must be at least twice the thickness of the image from which it is derived (e.g., 10 mm for a 5 mm slice thickness)

• No diffuse pontine gliomas

• No evidence of prior CNS bleeding

• Karnofsky performance status (PS) 50-100% (patients > 16 years of age)

• Lansky PS 50-100% (patients =< 16 years of age)

• Life expectancy >= 8 weeks

• Absolute neutrophil count (ANC) >= 1,000/µL

• Platelet count >= 100,000/µL (transfusion independent)

• Hemoglobin >= 8.0 g/dL (red blood cell [RBC] transfusions allowed)

• Creatinine clearance or radioisotope glomerular filtration rate >= 70mL/min OR serum creatinine based on age/gender as follows:

• 0.4 mg/dL (1 month to < 6 months of age)

• 0.5 mg/dL (6 months to < 1 year of age)

• 0.6 mg/dL (1 to < 2 years of age)

• 0.8 mg/dL (2 to < 6 years of age)

• 1.0 mg/dL (6 to < 10 years of age)

• 1.2 mg/dL (10 to < 13 years of age)

• 1.5 mg/dL (male) or 1.4mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) or 1.4mg/dL (female) (>= 16 years of age)

• Total bilirubin =< 1.5 times upper limit of normal (ULN) for age

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times ULN for age

• No evidence of dyspnea at rest

• No exercise intolerance

• Pulse oximetry > 94%, if determination is clinically indicated

• Seizure disorder is allowed provided it is well-controlled with anticonvulsants

• No uncontrolled infection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Recovered from all prior therapy

• No more than two prior treatments for high-grade glioma (i.e., one initial treatment and one treatment for relapse)

• More than 2 weeks since prior myelosuppressive chemotherapy (>= 6 weeks for nitrosoureas)

• At least 1 week since prior non-myelosuppressive chemotherapy, immunotherapy, or biologic therapy

• At least 2 weeks since prior local palliative radiotherapy (i.e., small port) to a symptomatic non-target lesion only

• At least 3 months since prior craniospinal radiotherapy

• At least 6 weeks since prior substantial bone marrow radiotherapy

• At least 6 months since prior allogeneic stem cell transplant (SCT) or rescue

• Patients who have undergone prior allogeneic SCT and who have graft-versus-host disease (GVHD) must have controlled GVHD that is =< grade 2

• At least 1 month since prior autologous SCT

• More than 1 week since prior growth factors (> 3 weeks for pegfilgrastim [Neulasta®])

• No other concurrent anticancer therapy, including chemotherapy or immunomodulating agents

• No other concurrent experimental agents or therapies

• No concurrent alternative or complimentary therapies

• No concurrent homeopathic medicines

• No concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (aspirin)

• No concurrent steroids as anti-emetics

• Concurrent steroids for treatment of increased intracranial pressure allowed if on a stable or decreasing dose for >= 1 week before study entry

• Concurrent radiotherapy to localized painful lesions allowed provided >= 1 measurable lesion is not irradiated

Related Conditions & MeSH terms

• Astrocytoma
• Childhood High-grade Cerebellar Astrocytoma
• Childhood High-grade Cerebral Astrocytoma
• Glioblastoma
• Glioma
• Oligodendroglioma
• Optic Nerve Glioma
• Recurrent Childhood Anaplastic Astrocytoma
• Recurrent Childhood Anaplastic Oligoastrocytoma
• Recurrent Childhood Anaplastic Oligodendroglioma
• Recurrent Childhood Brain Tumor
• Recurrent Childhood Cerebellar Astrocytoma
• Recurrent Childhood Cerebral Astrocytoma
• Recurrent Childhood Glioblastoma
• Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Intervention

Drug:
• cilengitide
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	Palmetto Health Richland	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	New York University Langone Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of California San Francisco Medical Center-Parnassus	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response to Cilengitide	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.	Up to 16 weeks
Secondary	Time to Tumor Progression (TTP)	The distribution of TTP will be analyzed separately using product limit (PL) estimate.	Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years
Secondary	Time to Treatment Failure (TTF)	The distribution of TTF will be analyzed separately using PL estimate.	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
Secondary	Time to Death (TTD)	The distribution of TTD will be analyzed separately using PL estimate.	Time from study enrollment to death from any cause, assessed up to 5 years
Secondary	Rate of Toxicity, Especially That of Symptomatic Intratumoral Hemorrhage (ITH) Assessed by Common Terminology Criteria for Adverse Events Version 4.0	Rate of individual toxicity including that of symptomatic ITH will be summarized in each course of treatment using standard descriptive statistical methods.	Up to 5 years
Secondary	Pharmacokinetic Parameter of Cilengitide in Plasma: Volume of Central Compartment (Vc)	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.	At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Secondary	Pharmacokinetic Parameter of Cilengitide in Plasma: Elimination Rate Constant (Ke)	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.	At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Secondary	Pharmacokinetic Parameter of Cilengitide in Plasma: Half-life (t1/2)	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.	At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Secondary	Pharmacokinetic Parameter of Cilengitide in Plasma: Systemic Clearance (Cl)	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.	At baseline and 1, 3, and 6 hours after the first dose of cilengitide
Secondary	Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by AUC	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.	At baseline
Secondary	Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by Systemic Clearance	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.	At Baseline
Secondary	Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by AUC	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.	At baseline
Secondary	Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by Systemic Clearance	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.	At baseline