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

NCT ID: NCT00679354

Last Updated: 2018-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2011-07-31

Brief 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.

Detailed 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.

Conditions

Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (cilengitide)

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.

Group Type: EXPERIMENTAL

cilengitide

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

cilengitide

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

EMD 121974; pharmacological studies

Eligibility Criteria

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tobey MacDonald

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Kaiser Permanente-Oakland

Oakland, California, United States

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Lombardi Comprehensive Cancer Center at Georgetown University

Washington D.C., District of Columbia, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

New York University Langone Medical Center

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Palmetto Health Richland

Columbia, South Carolina, United States

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Seattle Children's Hospital

Seattle, Washington, United States

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Countries

United States; Canada

Other Identifiers

NCI-2009-00339

Identifier Type: REGISTRY

Identifier Source: secondary_id

COG-ACNS0621

Identifier Type: -

Identifier Source: secondary_id

CDR0000595623

Identifier Type: -

Identifier Source: secondary_id

ACNS0621

Identifier Type: OTHER

Identifier Source: secondary_id

ACNS0621

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00339

Identifier Type: -

Identifier Source: org_study_id

NCT01648400

Identifier Type: -

Identifier Source: nct_alias