ACNS0222: A Phase II Study of Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood
| Phase | Type | Status | Age | Sponsor | Protocol ID |
|---|
| Phase II | Treatment | Active | 21 and under at diagnosis | COG | ACNS0222 |
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 6-7 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.
Objectives
Primary
- 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
- Evaluate the effect of combining motexafin gadolinium with daily fractionated radiotherapy on 1-year overall survival of these patients.
- Determine the toxicities of motexafin gadolinium in combination with radiotherapy in these patients.
Mechanism of Action
A synthetic metallotexaphyrin with radiosensitizing and chemosensitizing properties. Motexafin gadolinium accumulates in tumor cells preferentially due to their increased rates of metabolism, generating reactive oxygen species (ROS) intracellularly and lowering the tumor cell apoptotic threshold to ionizing radiation and chemotherapy.
Projected Accrual
A total of 60 patients will be accrued for this study.
Entry Criteria
Disease Characteristics:
- 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
Patient Characteristics:
Age
- Under 21 at time of diagnosis
Performance Status
- Karnofsky performance status 60-100% (age > 16 years)
- Lansky 60-100% (age ≤ 16 years)
Life Expectancy
- Life expectancy ≥ 8 weeks
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm³
- Platelet count ≥ 100,000/mm³ (transfusion independent)
- Hemoglobin ≥ 10 g/dL (RBC transfusions allowed)
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT < 1.5 times ULN
Renal
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal for age/gender (0.4-1.7 mg/dL)
Cardiovascular
Pulmonary
Other
- 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
Prior / Concurrent Therapy:
Biologic therapy
- No concurrent immunomodulating agents
Chemotherapy
- No concurrent anticancer chemotherapy
Endocrine therapy
- Concurrent steroids and anticonvulsants allowed
Radiotherapy
- No prior cranial radiotherapy
- No concurrent proton therapy
- No concurrent intensity-modulated radiotherapy
Surgery
Other
- No prior definitive therapy for this specific tumor
Outcomes
Primary Outcome(s)
- Event-free survival, defined as time to disease progression, disease relapse, occurrence of second neoplasm, or death from any cause at 1 year
Secondary Outcome(s)
- Overall survival, defined as time to death from any cause at 1 year
- Toxicity
Trial Contact Information
Rebecca Turner, MS, CCRP
Cincinnati Children's Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org
