Clinical trial NCT00679354: Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy
Official title: Cilengitide (EMD 121974) (IND# 59073) in Recurrent or Progressive and Refractory Childhood High-Grade Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-05-16
Enrollment: 30
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response to Cilengitide
timeFrame: Up to 16 weeks
Secondary outcomes:
measure: Time to Tumor Progression (TTP)
timeFrame: Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years
measure: Time to Treatment Failure (TTF)
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
measure: Time to Death (TTD)
timeFrame: Time from study enrollment to death from any cause, assessed up to 5 years
measure: Rate of Toxicity, Especially That of Symptomatic Intratumoral Hemorrhage (ITH) Assessed by Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: Up to 5 years
measure: Pharmacokinetic Parameter of Cilengitide in Plasma: Volume of Central Compartment (Vc)
timeFrame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
measure: Pharmacokinetic Parameter of Cilengitide in Plasma: Elimination Rate Constant (Ke)
timeFrame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
measure: Pharmacokinetic Parameter of Cilengitide in Plasma: Half-life (t1/2)
timeFrame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
measure: Pharmacokinetic Parameter of Cilengitide in Plasma: Systemic Clearance (Cl)
timeFrame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide
measure: Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by AUC
timeFrame: At baseline
measure: Pharmacogenetic Polymorphism in Drug Transporter Gene ABCB1 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
timeFrame: At Baseline
measure: Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by AUC
timeFrame: At baseline
measure: Pharmacogenetic Polymorphism in Drug Transporter Gene ABCG2 and Relate to Cilengitide Disposition as Measured by Systemic Clearance
timeFrame: At baseline
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center-Parnassus
state: California
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University
state: District of Columbia
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Chattanooga
country: United States
facility: T C Thompson Children's Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
Study officials:
affiliation: Children's Oncology Group
name: Tobey MacDonald
role: PRINCIPAL_INVESTIGATOR
References: