Capecitabine and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Nonmetastatic Brain Stem Glioma or High-Grade Glioma - Full Text View

Sponsor:	Pediatric Brain Tumor Consortium
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00357253

Purpose

RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Capecitabine may make tumor cells more sensitive to radiation therapy. Giving capecitabine together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with radiation therapy in treating young patients with newly diagnosed, nonmetastatic brain stem glioma or high-grade glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: capecitabine Other: pharmacological study Procedure: adjuvant therapy Procedure: magnetic resonance imaging Procedure: magnetic resonance spectroscopic imaging Radiation: radiation therapy	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas and High Grade Gliomas

Resource links provided by NLM:

MedlinePlus related topics: Cancer MRI Scans

Drug Information available for: Capecitabine

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) in combination with radiotherapy [ Designated as safety issue: Yes ]
Dose-limiting toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics of capecitabine RDT measured periodically during course 1 [ Designated as safety issue: No ]
Antitumor activity [ Designated as safety issue: No ]
Survival rate at 2 years [ Designated as safety issue: No ]
Radiographic changes in gliomas as measured by MRI, magnetic resonance spectroscopy (MRS), perfusion and diffusion MRI, and PET scans at baseline and periodically during study [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	January 2006
Estimated Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Estimate the maximum tolerated dose of capecitabine rapidly disintegrating tablets (RDT) administered concurrently with radiotherapy in young patients with newly diagnosed, nondisseminated intrinsic brain stem glioma or high-grade glioma.
Describe the dose-limiting toxicity in patients treated with this regimen.

Secondary

Describe the safety profile of this regimen.
Characterize the pharmacokinetics of capecitabine RDT in these patients.
Explore the exposure-response relationship for measures of safety and effectiveness using pharmacokinetic and pharmacodynamic models.
Describe the antitumor activity of this regimen observed in these patients.
Estimate distributions of progression-free survival and survival in patients treated with this regimen.
Characterize radiographic changes in tumor, using MRI, perfusion and diffusion MRI, and positron emission tomography (PET) scans, in patients treated with this regimen.

OUTLINE: This a multicenter, dose-escalation study of capecitabine rapidly disintegrating tablets (RDT).

Patients undergo radiotherapy once daily, 5 days a week, for approximately 6 weeks. Beginning within 24 hours of starting radiotherapy, patients also receive oral capecitabine RDT twice daily on days 1-21. Treatment with capecitabine RDT repeats every 21 days for 3 courses.

Cohorts of 3-6 patients receive escalating doses of capecitabine RDT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Beginning in week 12, patients receive capecitabine RDT at a fixed dose twice daily on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during course 1 for pharmacokinetic correlative studies. Patients also undergo MRI, and rapid perfusion/diffusion MRI at baseline and periodically during study for radiographic correlative studies.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

One of the following newly diagnosed, nondisseminated brain tumors:
- Intrinsic infiltrating brain stem glioma
  - Histopathologic diagnosis not required
- Histopathologically confirmed high-grade glioma, meeting all of the following criteria:
  - Underwent prior definitive surgery ≤ 28 days ago with incompletely resected disease
  - Any of the following subtypes allowed:
    - Anaplastic astrocytoma
    - Glioblastoma multiforme
    - Other high-grade glioma
No anaplastic oligodendroglioma

PATIENT CHARACTERISTICS:

Karnofsky performance scale (PS) 50-100% (if > 16 years of age) or Lansky PS 50-100% (if ≤ 16 years of age)
Absolute neutrophil count ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³ (transfusion independent)
Hemoglobin ≥ 8 g/dL (transfusion independent)
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age as follows:
- No more than 0.8 mg/dL (for patients 5 years of age and under)
- No more than 1 mg/dL (for patients 6-10 years of age)
- No more than 1.2 mg/dL (for patients 11-15 years of age)
- No more than 1.5 mg/dL (for patients over 15 years of age)
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT ≤ 5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled infection
No significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or other systemic disease
No known hypersensitivity to capecitabine or any of its components
No known dihydropyrimidine dehydrogenase (DPD) deficiency

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Prior dexamethasone and/or surgery allowed
No prior chemotherapy, radiotherapy, immunotherapy, or bone marrow transplantation
No other concurrent anticancer or experimental drug therapies or agents
No concurrent warfarin or sorivudine or its chemically related analogues (e.g., brivudine)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357253

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 412-692-7056
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
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030-2399
Contact: Susan M. Blaney, MD 832-822-1482 sblaney@txccc.org
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:	Susan M. Blaney, MD	Texas Children's Cancer Center
Investigator:	Lindsay B. Kilburn, MD	Texas Children's Cancer Center

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:	CDR0000484429, PBTC-021
Study First Received:	July 26, 2006
Last Updated:	January 13, 2010
ClinicalTrials.gov Identifier:	NCT00357253 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

untreated childhood brain stem glioma
childhood high-grade cerebral astrocytoma
untreated childhood cerebellar astrocytoma

Additional relevant MeSH terms:

Antimetabolites
Capecitabine
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Nervous System Diseases
Central Nervous System Neoplasms
Pharmacologic Actions

Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Glioma
Neoplasms, Neuroepithelial
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010