Brainstem Glioma
Conditions
Brief summary
This study evaluated the effect of capecitabine and concomitant radiation therapy in children with newly diagnosed brainstem gliomas.
Detailed 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.
Interventions
DRUGCapecitabine
Capecitabine was supplied as film-coated tablets.
RADIATIONRadiation therapy
Local irradiation using conformal, volume-based delivery techniques. The nominal energy of the X-rays was ≥ 4 MV.
Sponsors
Pediatric Brain Tumor Consortium
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Baseline to the end of the study (up to 20 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Baseline to the end of the study (up to 20 weeks) | 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. |
| Percentage of Participants With a Tumor Response | Baseline to the end of the study (up to 20 weeks) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine + Radiation Therapy 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. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 38 |
| Overall Study | Did Not Receive Study Medication | 1 |
| Overall Study | Failure to Return | 3 |
Baseline characteristics
| Characteristic | Capecitabine + Radiation Therapy |
|---|---|
| Age, Continuous | 7.5 years STANDARD_DEVIATION 3.69 |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 44 |
| serious Total, serious adverse events | 23 / 44 |
Outcome results
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.
Time frame: Baseline to the end of the study (up to 20 weeks)
Population: Intent-to-treat population: All enrolled participants who received at least 1 dose of capecitabine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine + Radiation Therapy | Progression-free Survival | 4.9 Months |
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.
Time frame: Baseline to the end of the study (up to 20 weeks)
Population: Intent-to-treat population: All enrolled participants who received at least 1 dose of capecitabine.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine + Radiation Therapy | Overall Survival | 10.3 Months |
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.
Time frame: Baseline to the end of the study (up to 20 weeks)
Population: Intent-to-treat population: All enrolled participants who received at least 1 dose of capecitabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine + Radiation Therapy | Percentage of Participants With a Tumor Response | 2.3 Percentage of participants |