Untreated Childhood Brain Stem Glioma
Conditions
Brief summary
This phase II trial is studying how well giving motexafin gadolinium together with radiation therapy works in treating young patients with pontine glioma. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as motexafin gadolinium, may make tumor cells more sensitive to radiation therapy. Giving motexafin gadolinium together with radiation therapy may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. Evaluate the effect of combining motexafin gadolinium with daily fractionated radiotherapy on 1-year event-free survival of pediatric patients with intrinsic pontine glioma (brain stem glioma). SECONDARY OBJECTIVES: I. Evaluate the effect of combining motexafin gadolinium with daily fractionated radiotherapy on 1-year overall survival of these patients. II. Determine the toxicities of motexafin gadolinium in combination with radiotherapy in these patients. OUTLINE: This is a multicenter study. Patients receive motexafin gadolinium IV over 5-10 minutes once daily (prior to radiotherapy) 5 days a week for 6 weeks. Patients undergo focal cranial radiotherapy once daily 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 3 years and then periodically thereafter.
Interventions
DRUGmotexafin gadolinium
Given IV
RADIATION3-dimensional conformal radiation therapy
Undergo focal cranial radiotherapy
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of intrinsic pontine glioma (brain stem glioma) * Clinical and radiographic (MRI) evidence of tumors that diffusely involve the brain stem (i.e., tumors that intrinsically \[\> 50% intra-axial\] involve the pons or pons and medulla, pons and midbrain, or entire brain stem) allowed * Tumor may contiguously involve the thalamus or upper cervical cord * No more than 1 lesion/mass present at diagnosis * Karnofsky performance status (PS) 60-100% (age \> 16 years) OR Lansky PS 60-100% (age ≤ 16 years) * Life expectancy ≥ 8 weeks * Absolute neutrophil count ≥ 1,000/mm³ * Platelet count ≥ 100,000/mm³ (transfusion independent) * Hemoglobin ≥ 10 g/dL (RBC transfusions allowed) * Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal for age/gender (0.4-1.7 mg/dL) * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT \< 1.5 times ULN * No known glucose-6-phosphate dehydrogenase (G6PD) deficiency * If family history suggestive of congenital hemolytic anemia, patient must be screened for G6PD with G6PD activity test prior to study entry * No biliary obstruction * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior definitive therapy for this specific tumor * No prior cranial radiotherapy * Concurrent steroids and anticonvulsants allowed * No concurrent proton therapy * No concurrent intensity-modulated radiotherapy * No concurrent anticancer chemotherapy * No concurrent immunomodulating agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One Year Event-free Survival (EFS) | One year after enrollment. | Percentage probability of being event-free at 1 year following enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | One year after enrollment. | Percentage probability of being alive 1 year following enrollment. |
| The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity. | One cycle of chemotherapy and radiation therapy; expected to be 42 days of treatment. | Occurrence of serious toxicity defined as any grade 4 hematologic toxicity that persists for more than 7 days or requires platelet transfusions for a time period exceeding 7 days; any grade 3 or 4 non-hematologic toxicity with the exception of grade 3 nausea or vomiting which can be controlled within 7 days; grade 3 skin reaction; grade 3 transaminitis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation and Motexafin Gadolinium Patients receive motexafin gadolinium IV over 5-10 minutes once daily (prior to radiotherapy) 5 days a week for 6 weeks. Patients undergo localized cranial radiotherapy once daily 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
motexafin gadolinium: Given IV
2-dimensional, 3-dimensional conformal, or intensity-modulated radiation therapy: Undergo localized cranial radiotherapy | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Ineligible for study | 2 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Radiation and Motexafin Gadolinium |
|---|---|
| Age, Continuous | 6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 42 Participants |
| Region of Enrollment Australia | 5 participants |
| Region of Enrollment Canada | 4 participants |
| Region of Enrollment United States | 55 participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 62 |
| serious Total, serious adverse events | 11 / 62 |
Outcome results
Primary
One Year Event-free Survival (EFS)
Percentage probability of being event-free at 1 year following enrollment.
Time frame: One year after enrollment.
Population: Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome. The 2 patients who are ineligible were excluded from the Outcome Measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation and Motexafin Gadolinium | One Year Event-free Survival (EFS) | 20 percent probability |
Secondary
Overall Survival (OS)
Percentage probability of being alive 1 year following enrollment.
Time frame: One year after enrollment.
Population: Only eligible patients are included therefore two patients were excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation and Motexafin Gadolinium | Overall Survival (OS) | 53 percent probability |
Secondary
The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.
Occurrence of serious toxicity defined as any grade 4 hematologic toxicity that persists for more than 7 days or requires platelet transfusions for a time period exceeding 7 days; any grade 3 or 4 non-hematologic toxicity with the exception of grade 3 nausea or vomiting which can be controlled within 7 days; grade 3 skin reaction; grade 3 transaminitis.
Time frame: One cycle of chemotherapy and radiation therapy; expected to be 42 days of treatment.
Population: Only eligible patients are included in the analysis, therefore two patients were excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation and Motexafin Gadolinium | The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity. | 31 Participants |