Phase 2
N=69
Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas
Untreated Childhood Anaplastic Astrocytoma · Untreated Childhood Anaplastic Oligodendroglioma · Untreated Childhood Brain Stem Glioma · Untreated Childhood Giant Cell Glioblastoma · Untreated Childhood Glioblastoma
Bottom Line
View on ClinicalTrials.gov: NCT00042991 ↗Enrolled (actual)
69
Serious AEs
43.5%
Results posted
Jul 2011
Primary outcome: Primary: Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy — 2; 0; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- gefitinib (Drug); radiation therapy (Radiation); pharmacological study (Other); laboratory biomarker analysis (Other)
- Age
- Pediatric, Adult · 3+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Feb 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy |
2; 0; 1 | — |
| PRIMARY Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas |
7.43 | — |
| PRIMARY Median Survival in Newly Diagnosed Brain Stem Gliomas |
12.12 | — |
| SECONDARY Change in Tumor Volume Measured on Fluid Attenuated Inversion Recovery (FLAIR) Imaging at Before the Protocol Therapy Started and at Two Weeks After Completion of Radiation |
-14.03 | <0.0001 sig |
| SECONDARY Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation |
0.35 | 0.0546 |
| SECONDARY Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation |
-0.41 | <0.0001 sig |
| SECONDARY Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation |
0.72 | 0.18 |
| SECONDARY Mean Tumor to Gray Matter Ratio Measured at Baseline |
0.55 | — |
| SECONDARY Mean Tumor to White Matter Ratio Measured at Baseline |
1.16 | — |
| SECONDARY Peak Serum Concentration of Gefitinib (Cmax) |
1.10; 0.83; 0.44; 1.89 | — |
| SECONDARY Elimination Half Life of Gefitinib (t1/2) |
15.2; 17.6; 9.9; 10.4 | — |
| SECONDARY Clearance of Gefitinib (Cl) |
15.2; 20.9; 12.8; 15.0 | — |
| SECONDARY Time of Maximum Clearance of Gefitinib (Tmax) |
3.2; 4.2; 4.9; 4.2 | — |
| SECONDARY Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC) |
16.4; 11.8; 5.3; 25.3 | — |
| SECONDARY Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification |
5 | — |
Summary
Biological therapies such as gefitinib may interfere with the growth of the tumor cells and may make the tumor cells more sensitive to radiation therapy. This phase I/II trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma.
Eligibility Criteria
Inclusion Criteria
- Tumor:
- Phase I: newly diagnosed non-disseminated diffuse intrinsic brainstem tumor or newly diagnosed (diagnostic scan must be within 4 weeks prior to treatment initiation), incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma) (STMG); the STMG group must have residual tumor evident on postoperative MRI or CT
- Phase II: only newly diagnosed non-disseminated diffuse intrinsic brain stem glioma patients are eligible
- Performance status: Karnofsky or Lansky >= 50% assessed within two weeks prior to registration
- Prior/concurrent therapy:
- Chemotherapy: no prior therapy allowed, including prior gefitinib treatment
- Radiation therapy (XRT): no prior therapy allowed
- Bone marrow transplant: none prior
- Anti-convulsants: patients with brain stem glioma (BSG) receiving EIACD will not be eligible; patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD) and will be stratified by use of EIACDs
- Growth factors: off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
- ANC > 1,000/ul
- Platelets > 100,000/ul (transfusion independent)
- Hemoglobin > 8g/dl (may be transfused)
- Patients may have bone marrow involvement by disease
- Creatinine 70 ml/min/1.73m^2
- Bilirubin < 1.5 x normal institutional normal for age
- SGPT (ALT) < 3 x institutional normal for age
- Pregnant and/or lactating patients are excluded; patients of childbearing potential should not become pregnant and should not father a child during treatment with gefitinib; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Signed informed consent according to institutional guidelines must be obtained prior to study entry
Exclusion Criteria
- Patients with evidence of intramural hemorrhage on a scan obtained prior to enrollment or after enrollment, before treatment
- Patients with BSG must not be taking enzyme-inducing anticonvulsant drugs
- Patient must not be receiving any other anticancer or experimental drug therapy
- Patient must have no uncontrolled infection
- Patients with significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease are ineligible; patients with deep venous or arterial thrombosis within 6 weeks of study entry are ineligible
- Patients with disseminated disease are not permitted
- Patients with spinal disease requiring craniospinal radiation are not eligible
- Patients with completely resected supratentorial malignant gliomas patients are ineligible
Data sourced from ClinicalTrials.gov (NCT00042991). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.