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

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

Detailed Description
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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.

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

Conditions
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Brainstem Glioma

Intervention / Treatment
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* Drug: Capecitabine
* Radiation: Radiation therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine + radiation therapy<br>Participants received 9 weeks of capecitabine 650 mg/m^2 orally (po) twice daily (bid) plus radiation therapy (180 cGy/day 5 days a week, total target dose of 56 Gy) followed by a 2-week rest period. Participants then received 3 cycles of capecitabine 1250 mg/m^2 po bid for 14 days followed by a 7-day rest period without radiation therapy. | Drug: Capecitabine<br>* Capecitabine was supplied as film-coated tablets.<br>* Other names: Xeloda;Radiation: Radiation therapy<br>* Local irradiation using conformal, volume-based delivery techniques. The nominal energy of the X-rays was ≥ 4 MV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) |