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

• ClinicalTrials.gov Identifier: NCT00532948
• Recruitment Status: Completed
• First Posted: September 21, 2007
• Results First Posted: March 15, 2016
• Last Update Posted: December 7, 2016
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Glioma	Drug: capecitabine [Xeloda]	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: 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
• Study Start Date: May 2007
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: October 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Drug: capecitabine [Xeloda]; 500mg/m2 po bid (starting dose)

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose (MTD) of Capecitabine. [ Time Frame: Upto 11 weeks. ]
   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.
2. Dose Limiting Toxicities (DLTs) [ Time Frame: Upto 11 weeks ]
   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).
3. Number of Participants With Adverse Events (AE) [ Time Frame: Up to 06 years ]
   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.
4. Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters [ Time Frame: Up to 06 years ]
   For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils.
5. Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters [ Time Frame: Up to 06 years ]
   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 :

1. 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 ]
   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).
2. 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 ]
   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).
3. 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 ]
   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).
4. Anti Tumor Activity [ Time Frame: Up to 6 years ]
   Tumor response refers to the best response prior to failure (disease progression, death or second malignancy).

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: NO18517
• First Posted: September 21, 2007
• Results First Posted: March 15, 2016
• Last Update Posted: December 7, 2016
• Last Verified: October 2016

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