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

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

This study evaluated the effect of capecitabine and concomitant radiation therapy in children with newly diagnosed brainstem gliomas.

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.

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.