A Study of Capecitabine (Xeloda®) and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas

Brainstem Glioma Clinical Trial

Official title:

A Phase II Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01118377
• Other study ID #: NO21125
• Secondary ID: PBTC-030
• Status: Completed
• Phase: Phase 2
• First received: April 15, 2010
• Last updated: February 4, 2014
• Start date: May 2007
• Est. completion date: April 2013

Study information

• Verified date: February 2014
• 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 study evaluated the effect of capecitabine and concomitant radiation therapy in children with newly diagnosed brainstem gliomas.

Description:

The open-label phase 2 study NO21125 (NCT01118377) evaluated the progression-free survival, safety, and pharmacokinetics of capecitabine (Xeloda®) rapidly disintegrating tablets and concomitant radiation therapy in children and adolescent patients with newly diagnosed brainstem glioma. There were 2 phases to the study: A 9-week radiation phase, followed by a 2-week rest period, and a 9-week post-radiation phase. In the radiation phase, capecitabine 650 mg/m^2 was administered orally twice daily for 9 weeks. Concomitantly, patients received radiation therapy (180 cGy fractions) 5 days a week for a total target dose of 56 Gy. During the 9-week post-radiation phase of the study, capecitabine 1250 mg/m^2 was administered orally twice daily for 14 days followed by a 7-day rest period. This cycle of 14 days treatment followed by 7 days rest was repeated 2 additional times. The dose could be adjusted according to toxicity and body surface area.

The single-arm phase 1 study NO18517 (NCT00532948) assessed the maximum tolerated dose and dose-limiting toxicities of capecitabine (Xeloda®) administered concurrently with radiation therapy in children with newly diagnosed diffuse intrinsic brain stem gliomas and high grade gliomas. Patients in the phase 1 study NO18517 who were diagnosed with intrinsic brainstem glioma and who were treated at the established maximum tolerated dose of capecitabine 650 mg/m^2/dose twice a day were included in the analyses of the phase 2 study NO21125.

The efficacy and safety results of study NO21125 are reported below.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: April 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 17 Years

Eligibility

Inclusion Criteria:

• Pediatric and adolescent patients = 3 to < 18 years of age.

• Patients must have a newly diagnosed non-disseminated intrinsic infiltrating brainstem glioma.

• Karnofsky Performance Scale (if > 16 years of age) or Lansky Performance Score (if = 16 years of age) = 50% assessed within 2 weeks prior to registration to study.

• Patients must not have received any prior chemotherapy or bone marrow transplant for the treatment of brainstem glioma. Prior dexamethasone and/or surgery are allowed.

• Adequate organ function.

Exclusion Criteria:

• Patients receiving any other anticancer or experimental drug therapy.

• Patients with uncontrolled infection.

• Known dihydropyrimidine dehydrogenase (DPD) deficiency.

Study Design

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

Related Conditions & MeSH terms

• Brainstem Glioma
• Glioma

Intervention

Drug:
• Capecitabine
Capecitabine was supplied as film-coated tablets.

Radiation:
• Radiation therapy
Local irradiation using conformal, volume-based delivery techniques. The nominal energy of the X-rays was = 4 MV.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Pediatric Brain Tumor Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Progression-free survival was defined as the time from the initiation of treatment to the earliest date of failure (disease progression, death from any cause, or a second malignancy) or to the last assessment date for patients who did not fail. Disease progression was defined as progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (eg, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, weaning of steroids, radiation necrosis, etc); or a greater than 25% increase in the bi-dimensional measurement of the tumor, as compared with the previous scan; or the appearance of a new lesion; or an increase in the doses of dexamethasone required to maintain stable neurologic status or imaging.	Baseline to the end of the study (up to 20 weeks)	No
Secondary	Overall Survival	Overall survival was defined as the time from the initiation of therapy to the date of death from any cause or to the date the patient was last known to be alive for surviving patients.	Baseline to the end of the study (up to 20 weeks)	No
Secondary	Percentage of Participants With a Tumor Response	Tumor response was defined as either a complete response or a partial response prior to failure (disease progression, death from any cause, or a second malignancy). A complete response was defined as the complete disappearance on magnetic response imaging of all enhancing tumor and mass effect on a stable or decreasing dose of dexamethasone (or only receiving adrenal replacement doses) accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks. A partial response was defined as a greater than or equal to 50% reduction in tumor size by bi-dimensional measurement on a stable or decreasing dose of dexamethasone accompanied by a stable or improving neurologic examination that was maintained for at least 12 weeks.	Baseline to the end of the study (up to 20 weeks)	No