AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00326664
First received: May 16, 2006
Last updated: September 16, 2014
Last verified: April 2014
  Purpose

This phase I trial is studying the side effects and best dose of AZD2171 in treating young patients with recurrent, progressive, or refractory primary CNS tumors. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.


Condition Intervention Phase
Childhood Atypical Teratoid/Rhabdoid Tumor
Childhood Central Nervous System Germ Cell Tumor
Childhood Grade I Meningioma
Childhood Grade II Meningioma
Childhood Grade III Meningioma
Childhood High-grade Cerebral Astrocytoma
Childhood Infratentorial Ependymoma
Childhood Low-grade Cerebral Astrocytoma
Childhood Oligodendroglioma
Childhood Spinal Cord Neoplasm
Childhood Supratentorial Ependymoma
Recurrent Childhood Brain Stem Glioma
Recurrent Childhood Brain Tumor
Recurrent Childhood Cerebellar Astrocytoma
Recurrent Childhood Cerebral Astrocytoma
Recurrent Childhood Ependymoma
Recurrent Childhood Medulloblastoma
Recurrent Childhood Pineoblastoma
Recurrent Childhood Subependymal Giant Cell Astrocytoma
Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
Recurrent Childhood Visual Pathway and Hypothalamic Glioma
Drug: cediranib maleate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial of AZD2171 in Children With Recurrent or Progressive Central Nervous System (CNS) Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose, defined as the dose at which the model estimates that 25% of patients will experience dose-limiting toxicity as measured by NCI CTCAE v4.0 [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
    Estimated using the modified Continual Reassessment Method (CRM).


Enrollment: 52
Study Start Date: March 2006
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate)
Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Given orally
Other Names:
  • AZD2171
  • Recentin

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of AZD2171 in pediatric patients with recurrent, progressive, or refractory primary CNS tumors.

II. Describe the toxicity profile and dose-limiting toxicities of AZD2171 in these patients.

SECONDARY OBJECTIVES:

I. Characterize inter-patient variability in the pharmacokinetics of AZD2171 in these patients.

II. Describe changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) in patients treated with AZD2171 at different dose levels.

III. Correlate changes in CECs, CEPs, plasma, serum, and urine levels of proteins with angiogenesis, including vascular endothelial growth factor (VEGF) and VEGF receptor, in patients treated with AZD2171 at different dose levels.

IV. Correlate changes in CECs, CEPs, and angiogenic modulators with changes in magnetic resonance (MR) perfusion.

V. Obtain preliminary evidence of biologic activity of AZD2171 by evaluating alterations in tissue perfusion, tumor blood flow, and metabolic activity using MR perfusion and diffusion imaging, and positron-emission tomography, and correlating these findings with changes in tumor size by standard MRI.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent enzyme-inducing anticonvulsant drugs (yes vs no).

Patients receive oral AZD2171 once daily on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

For each stratum, cohorts of 2-6 patients receive escalating doses of AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients per stratum are enrolled and treated at the MTD.

After completion of study, patients are followed at 30 days.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed primary CNS tumor

    • Histologically benign brain tumors (e.g., low-grade glioma) allowed
    • Histological requirement waived for intrinsic brain stem or diffuse optic pathway tumors, but must have clinical and/or radiographic evidence of progression
  • Recurrent, progressive, or refractory disease
  • Absolute neutrophil count >= 1,000/mm^3 (unsupported)
  • Platelet count >= 75,000/mm^3 (unsupported)
  • Creatinine =< 1.5 times upper limit of normal (ULN) OR glomerular filtration rate >= 70 mL/min
  • Bilirubin =< 1.5 times ULN
  • ALT =< 2.5 times ULN
  • Urine dipstick or urinalysis < 1+ protein
  • Albumin >= 3 g/dL
  • Karnofsky performance status (PS) 60-100% (> 16 years of age) OR Lansky PS 60-100% (=< 16 years of age)
  • Karnofsky/Lansky PS 70-100% for patients at increased risk for compromised LVEF
  • Hemoglobin >= 8 g/dL (transfusion support allowed)
  • No overt renal, hepatic, cardiac, or pulmonary disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • QTc prolongation =< 500 msec
  • No other significant ECG abnormality within the past 14 days
  • No clinically significant, unrelated, systemic illness, including serious infections or significant cardiac, pulmonary, hepatic, or other organ dysfunction, that would preclude study participation
  • No uncontrolled hypertension

    • Defined as systolic and diastolic BP > 95th percentile for age (ages 1-17)
    • Defined as BP > 140/90 (ages 18 and older)
  • No New York Heart Association class III or IV disease and Karnofsky/Lansky PS < 70

    • Class II disease controlled with treatment and increased monitoring is allowed
  • Recovered from all prior therapy
  • No prior AZD2171
  • At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas)
  • More than 1 weeks since prior investigational or biologic agents

    • If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration
  • No concurrent drugs or biologics with proarrhythmic potential
  • More than 3 months since last fraction of craniospinal radiotherapy or total-body irradiation
  • More than 4 weeks since last fraction of focal irradiation to symptomatic metastatic sites
  • At least 6 months since prior allogeneic bone marrow transplantation
  • At least 3 months since prior autologous bone marrow or stem cell transplantation
  • At least 1 week since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa (2 weeks for pegfilgrastim)
  • No other concurrent investigational agents
  • Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose for ≥ 1 week before study entry
  • No concurrent chemotherapy
  • No concurrent routine use of G-CSF, GM-CSF, or epoetin alfa
  • Able to swallow tablets
  • Any neurologic deficits must be stable for >= 1 week
  • If the investigational or biologic agent has a prolonged half-life (> 48 hours), then these patients must be discussed with the study chair prior to registration

Exclusion Criteria:

  • No known curative therapy available
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00326664

Locations
United States, California
UCSF-Mount Zion
San Francisco, California, United States, 94115
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60611
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Pediatric Brain Tumor Consortium
Memphis, Tennessee, United States, 38105
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Investigators
Principal Investigator: Mark Kieran Pediatric Brain Tumor Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00326664     History of Changes
Other Study ID Numbers: NCI-2009-00709, NCI-2009-00709, CDR0000476579, PBTC-020, PBTC-020, U01CA081457
Study First Received: May 16, 2006
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Meningioma
Astrocytoma
Glioma
Ependymoma
Oligodendroglioma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Medulloblastoma
Neoplasms
Rhabdoid Tumor
Optic Nerve Glioma
Brain Neoplasms
Spinal Cord Neoplasms
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Neoplasms, Complex and Mixed
Optic Nerve Neoplasms
Cranial Nerve Neoplasms
Peripheral Nervous System Neoplasms
Cranial Nerve Diseases
Optic Nerve Diseases

ClinicalTrials.gov processed this record on September 22, 2014