A Study of Xeloda (Capecitabine) Plus Radiation Therapy in Children With Newly Diagnosed Gliomas

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00532948
First received: September 20, 2007
Last updated: February 17, 2016
Last verified: October 2015
  Purpose
This single arm study will assess the maximum tolerated dose, and dose-limiting toxicities, of Xeloda administered concurrently with radiation therapy, in children with newly diagnosed diffuse intrinsic brain stem gliomas and high grade gliomas. Xeloda will be administered twice daily, at a starting dose of 500mg/m2 bid, beginning within 24 hours of the start of radiation therapy. Subsequent dose escalations will be in increments of 30%, using a standard dose escalation schema. Post-radiation therapy with Xeloda will continue after a 2 week break. The anticipated time on study treatment is 3-12 months, and the target sample size will not exceed 30 evaluable patients.

Condition Intervention Phase
Glioma
Drug: capecitabine [Xeloda]
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose-escalation Study of Xeloda Plus Radiation Therapy in Pediatric Patients With Newly Diagnosed Non-disseminated, Intrinsic Brainstem Gliomas and High Grade Gliomas.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Capecitabine. [ Time Frame: Upto 11 weeks. ] [ Designated as safety issue: No ]
    The MTD was the dose level at which six evaluable patients had been treated and at most one patient experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 patients experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.

  • Dose Limiting Toxicities (DLTs) [ Time Frame: Upto 11 weeks ] [ Designated as safety issue: No ]
    DLT was defined as any of the following events occurring during the 11 week dose-finding period: any event that leads to interruption of planned radiation for 5 consecutive days or 10 days total; Grade 4 neutropenia or thrombocytopenia; Grade 3 thrombocytopenia that required a platelet transfusion on 2 or more occasions; any Grade 3 or 4 non-hematologic toxicity (with the exception of grade 3 nausea or vomiting of less than 5 days duration, Grade 3 transaminases that returned to baseline value within 7 days of study drug interruption and that did not recur upon re-challenge with study drug, and/or Grade 3 fever or infection of <5 days duration); Grade 2 non-hematologic toxicities that persisted for >7 days and required treatment interruption, or any other capecitabine-related adverse events that required need for dose reduction or permanent cessation of therapy, interruption of study drug for >7 days or recurred on re-challenge with capecitabine rapidly disintegrating tablets (RDTs).

  • Number of Participants With Adverse Events (AE) [ Time Frame: Up to 06 years ] [ Designated as safety issue: No ]
    An AE is an unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was monitored and graded according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Adverse events that were not included in the CTCAEv3.0 were reported and graded under the other AE within the appropriate category.

  • Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters [ Time Frame: Up to 06 years ] [ Designated as safety issue: No ]
    For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils.

  • Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters [ Time Frame: Up to 06 years ] [ Designated as safety issue: No ]
    For blood chemistry, the parameters assessed were: Sodium, potassium, calcium, magnesium, chloride, bicarbonate, total protein, albumin, alkaline phosphatase, alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), Lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, indirect bilirubin, creatinine (serum creatinine or creatinine clearance), glucose.


Secondary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
    The maximum observed plasma concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).

  • Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
    Tmax is the corresponding time at which Cmax occurs of capecitabine and its metabolites.Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).

  • The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) [ Time Frame: Day 1 and Day 14 ] [ Designated as safety issue: No ]
    AUC last concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).

  • Anti Tumor Activity [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Tumor response refers to the best response prior to failure (disease progression, death or second malignancy).


Enrollment: 24
Study Start Date: May 2007
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: capecitabine [Xeloda]
500mg/m2 po bid (starting dose)

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients >=3 and <=21 years of age;
  • newly diagnosed non-disseminated brainstem glioma or non-disseminated high grade glioma;
  • Karnofsky (if >16 years) or Lansky (if < 16 years) Performance Scale of >=50%;
  • adequate organ function.

Exclusion Criteria:

  • previous chemotherapy, radiation therapy, immunotherapy or bone marrow transplant;
  • uncontrolled infection;
  • known DPD deficiency.
  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: NCT00532948

Locations
United States, California
San Francisco, California, United States, 94143-0780
United States, District of Columbia
Washington, District of Columbia, United States, 20010
United States, Illinois
Chicago, Illinois, United States, 60614
United States, Massachusetts
Boston, Massachusetts, United States, 02115-6084
United States, North Carolina
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh, Pennsylvania, United States, 15261
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00532948     History of Changes
Other Study ID Numbers: NO18517 
Study First Received: September 20, 2007
Results First Received: December 28, 2015
Last Updated: February 17, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 26, 2016