AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors - Full Text View

Sponsors and Collaborators:	Pediatric Brain Tumor Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00326664

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: cediranib maleate	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Cediranib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Clinical Trial of AZD2171 in Children With Recurrent or Progressive Central Nervous System (CNS) Tumors

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

Primary Outcome Measures:

Maximum tolerated dose as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Toxicity profile and dose-limiting toxicities as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetic interpatient variability of AZD2171 as measured by liquid chromatographic assay with mass spectrometry detection at baseline and on day 28 of course 1 [ Designated as safety issue: No ]
Changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) at different dose levels [ Designated as safety issue: No ]
Correlation of changes in CECs, CEPs, plasma, serum, and urine levels of proteins at different dose levels of AZD2171 with angiogenesis [ Designated as safety issue: No ]
Changes in CECs, CEPs, and angiogenic modulators as measured by magnetic resonance (MR) perfusion [ Designated as safety issue: No ]
Biologic activity of AZD2171, in terms of altered tissue perfusion, tumor blood flow, and metabolic activity as measured by MR perfusion and diffusion imaging and positron-emission tomography [ Designated as safety issue: No ]
Correlation of biologic findings by advanced imaging techniques with changes in tumor size by standard MRI [ Designated as safety issue: No ]

Estimated Enrollment:	55
Study Start Date:	March 2006
Estimated Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of AZD2171 in pediatric patients with recurrent, progressive, or refractory primary CNS tumors.
Describe the toxicity profile and dose-limiting toxicities of AZD2171 in these patients.

Secondary

Characterize inter-patient variability in the pharmacokinetics of AZD2171 in these patients.
Describe changes in circulating endothelial cells (CECs) and circulating endothelial cell precursors (CEPs) in patients treated with AZD2171 at different dose levels.
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.
Correlate changes in CECs, CEPs, and angiogenic modulators with changes in magnetic resonance (MR) perfusion.
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.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

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
No known curative therapy available

PATIENT CHARACTERISTICS:

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
Absolute neutrophil count ≥ 1,000/mm³ (unsupported)
Platelet count ≥ 75,000/mm³ (unsupported)
Hemoglobin ≥ 8 g/dL (transfusion support allowed)
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
Able to swallow tablets
No overt renal, hepatic, cardiac, or pulmonary disease
Any neurologic deficits must be stable for ≥ 1 week
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
- Defnined 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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
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
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
No concurrent drugs or biologics with proarrythmic potential

Contacts and Locations

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

Locations

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center	Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi 877-827-3222
United States, District of Columbia
Children's National Medical Center	Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Clinical Trials Office - Children's National Medical Center 202-884-2549
United States, Illinois
Children's Memorial Hospital - Chicago	Recruiting
Chicago, Illinois, United States, 60614
Contact: Stewart Goldman, MD 773-880-4562
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Mark W. Kieran, MD, PhD 617-632-4907
United States, North Carolina
Duke Comprehensive Cancer Center	Recruiting
Durham, North Carolina, United States, 27710
Contact: Clinical Trials Office - Duke Comprehensive Cancer Center 888-275-3853
United States, Pennsylvania
Children's Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Peter C. Phillips, MD 215-590-2107
Children's Hospital of Pittsburgh	Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Clinical Trials Office - Children's Hospital of Pittsburgh 412-692-5573
United States, Tennessee
St. Jude Children's Research Hospital	Recruiting
Memphis, Tennessee, United States, 38105
Contact: Clinical Trials Office - St. Jude Children's Research Hospital 901-595-4644
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Trials Office - Dan L. Duncan Cancer Center at Baylor 713-798-1297
United States, Washington
Children's Hospital and Regional Medical Center - Seattle	Recruiting
Seattle, Washington, United States, 98105
Contact: Jeffrey R. Geyer, MD 206-987-6664

Sponsors and Collaborators

Pediatric Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:	Mark W. Kieran, MD, PhD	Dana-Farber Cancer Institute
Investigator:	Susan Chi, MD	Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000476579, PBTC-020
Study First Received:	May 16, 2006
Last Updated:	February 20, 2009
ClinicalTrials.gov Identifier:	NCT00326664 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

childhood central nervous system germ cell tumor
childhood oligodendroglioma
recurrent childhood brain stem glioma
recurrent childhood brain tumor
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
childhood spinal cord neoplasm
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
recurrent childhood ependymoma

recurrent childhood medulloblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma
childhood atypical teratoid/rhabdoid tumor
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
childhood infratentorial ependymoma
childhood supratentorial ependymoma
recurrent childhood pineoblastoma
recurrent childhood subependymal giant cell astrocytoma

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Rhabdoid Tumor
Astrocytoma
Spinal Cord Neoplasm
Brain Tumor, Childhood
Central Nervous System Neoplasms
Recurrence
Ependymoma
Brain Neoplasms

Neuroectodermal Tumors
Brain Stem Glioma, Childhood
Medulloblastoma
Neuroepithelioma
Spinal Cord Neoplasms
Oligodendroglioma
Meningioma
Glioma
Nervous System Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Nervous System Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009