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

Sponsor:	Pediatric Brain Tumor Consortium
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Pediatric Brain Tumor Consortium
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 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	Phase I

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:

MedlinePlus related topics: Cancer

Drug Information available for: Cediranib

U.S. FDA Resources

Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:

Toxicity [ Time Frame: From day 1 of treatment until 30 days after the last dose of the drug ] [ Designated as safety issue: Yes ]
Dose-limiting toxicities of 20 mg/m2 dose of AZD2171 [ Time Frame: First six weeks ] [ Designated as safety issue: Yes ]
Pharmacokinetics [ Time Frame: Day 28 of course 1 ] [ Designated as safety issue: No ]
Blood samples will be collected from study participants on day 28 of course 1 for pharmacokinetic studies.
Maximum-tolerated dose [ Time Frame: First six weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Change from baseline in angiogenic markers vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) [ Time Frame: Baseline and on treatment ] [ Designated as safety issue: No ]
Blood and urine samples will be drawn prior to course 1, once between days 7-14 of course 1 and after courses 2, 4, 6, 9, and 12 and at the discontinuation of completion of treatment.
Correlation of imaging parameters with progression-free survival [ Time Frame: From day 1 of treatment until progression, death or 30 days since the last treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	55
Study Start Date:	March 2006
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Study participants receive 20 mg/m2 orally once per day for four weeks (one course). In the absence of toxicity or disease progression, treatment may continue for 13 courses (approximately 1 year). Study participants in the dose escalation phase of the study (completed 24AUG2009) received 20, 25, 32, or 40 mg/m2 orally once per day in stratum I (patients not on enzyme inducing anticonvulsant drugs (EIACD)) or 15 or 20 mg/m2 orally once per day in stratum II (patients on EIACD) for four weeks (one course). In the absence of toxicity or disease progression, treatment may continue for 13 courses (approximately 1 year).

Other Names:

AZD2171 maleate
Recentin

Detailed Description:

OBJECTIVES:

Primary

Evaluate the safety of the 20 mg/m2/day dose of AZD2171 in pediatric patients with recurrent, progressive, or refractory primary CNS tumors (added 08SEP2010)
Estimate the maximum tolerated dose of AZD2171 (completed 24AUG2009).
Describe the toxicity profile and dose-limiting toxicities of AZD2171 in these patients.
Characterize the pharmacokinetics of 20 mg/m2/day of AZD2171 in these patients (added 08SEP2010)

Secondary

Evaluate changes in plasma, serum, and urine levels of proteins associated with angiogenesis, including vascular endothelial growth factor (VEGF) and VEGF receptor, in patients treated with AZD2171.
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 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.

After completion of treatment, patients are followed for 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
- 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

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 proarrhythmic 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, 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 412-692-7056
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

Sponsors and Collaborators

Pediatric Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Mark W. Kieran, MD, PhD

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

Responsible Party:	James M. Boyett (Executive Director Operations and Biostatistics Center for the PBTC), Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:	NCT00326664 History of Changes
Other Study ID Numbers:	CDR0000476579, U01CA081457, PBTC-020
Study First Received:	May 16, 2006
Last Updated:	June 13, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pediatric Brain Tumor Consortium:

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

Additional relevant MeSH terms:

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

ClinicalTrials.gov processed this record on February 09, 2012