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

Glioma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00532948
• Other study ID #: NO18517
• Status: Completed
• Phase: Phase 1
• First received: September 20, 2007
• Last updated: February 17, 2016
• Start date: May 2007
• Est. completion date: April 2013

Study information

• Verified date: October 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• capecitabine [Xeloda]
500mg/m2 po bid (starting dose)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Capecitabine.	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.	Upto 11 weeks.	No
Primary	Dose Limiting Toxicities (DLTs)	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).	Upto 11 weeks	No
Primary	Number of Participants With Adverse Events (AE)	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.	Up to 06 years	No
Primary	Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters	For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils.	Up to 06 years	No
Primary	Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters	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.	Up to 06 years	No
Secondary	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])	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).	Day 1 and Day 14	No
Secondary	Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL)	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).	Day 1 and Day 14	No
Secondary	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)	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).	Day 1 and Day 14	No
Secondary	Anti Tumor Activity	Tumor response refers to the best response prior to failure (disease progression, death or second malignancy).	Up to 6 years	No