Phase 2
N=97
Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma
Childhood Cerebral Anaplastic Astrocytoma · Childhood Oligodendroglioma · Childhood Spinal Cord Neoplasm · Recurrent Childhood Brain Stem Glioma · Recurrent Childhood Ependymoma
Bottom Line
View on ClinicalTrials.gov: NCT00381797 ↗Enrolled (actual)
97
Serious AEs
40.2%
Results posted
Jan 2013
Primary outcome: Primary: Objective Response Rate Sustained for ≥ 8 Weeks — 0; 0; 0; 0 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bevacizumab (Biological); Fludeoxyglucose F-18 (Radiation); Irinotecan Hydrochloride (Drug)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Oct 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate Sustained for ≥ 8 Weeks |
0; 0; 0; 0 | — |
| PRIMARY Sustained Disease Stabilization Rate Associated With Bevacizumab and Irinotecan in Patients With Recurrent or Progressive Low-grade Glioma (Stratum E) |
23 | — |
| SECONDARY Number of Study Participants With Grade 3 or 4 Treatment-related Toxicity |
8; 4; 4; 6; 22 | — |
| SECONDARY Cumulative Incidence of Sustained Objective Responses |
0; 0; 0; 0; 0.058 | — |
| SECONDARY Progression-free Survival |
4.20; 2.35; 2.48; 2.15 | — |
| SECONDARY Change in Perfusion Ratio Between the Baseline and Day 15 Brain Imaging |
-0.14; -1.98; -0.42 | — |
| SECONDARY Change in Diffusion Ratio Between the Baseline and Day 15 Brain Image |
-0.34; -0.17; 0.11; -0.11 | — |
| SECONDARY Association of Log-transformed Tumor Volume Based on FLAIR With Progression-free Survival (PFS) Using Hazard Ratio Estimates |
1.47; 1.76 | — |
| SECONDARY Association of Log-transformed Tumor Enhancing Volume With Progression-free Survival (PFS) Using Hazard Ratio Estimates |
1.65; 1.16 | — |
| SECONDARY Association of Log-transformed Volume of Cystic Necrosis With Progression-free Survival (PFS) Using Hazard Ratio Estimates |
2.56; 1.09 | — |
| SECONDARY Association of Log-transformed Tumor Diffusion Ratio With Progression-free Survival (PFS) Using Hazard Ratio Estimates |
4.41; 1.82 | — |
| SECONDARY Association of Log-transformed Tumor Perfusion Ratio With Progression-free Survival (PFS) Using Hazard Ratio Estimates |
— | — |
| SECONDARY Volume of Distribution |
1729 | — |
| SECONDARY Systemic Clearance |
9.43 | — |
| SECONDARY Terminal Half-life |
125.2 | — |
| SECONDARY Change in Vascular Endothelial Growth Factor Receptor-2 (VEGF-R2) Expression in Peripheral Blood Mononuclear Cells (PBMC) From Baseline to Day-15 |
-0.37; -0.21; -0.003; 0.24; 1.70 | — |
| SECONDARY Descriptive Statistics for the Changes in Vascular Endothelial Growth Factor Receptor-2 (VEGF-R2) Expression in Peripheral Blood Mononuclear Cells (PBMC) Concurrently Measured With the Changes in Perfusion From Magnetic Resonance Imaging |
-1.12; -1.20 | — |
| SECONDARY Descriptive Statistics for the Change of Perfusion in Magnetic Resonance Imaging Concurrently Measured With the Change in Vascular Endothelial Growth Factor Receptor-2 (VEGF-R2) Expression in Peripheral Blood Mononuclear Cells (PBMC) |
-1.60; -1.54 | — |
| SECONDARY Correlation of the Change in Vascular Endothelial Growth Factor Receptor-2 (VEGF-R2) Expression in Peripheral Blood Mononuclear Cells (PBMC) From Baseline With the Change in Perfusion From Magnetic Resonance Imaging |
0.5; -0.50 | — |
| SECONDARY Number of Patients With High Hypoxia Inducible Factor-2alpha Expression at Baseline |
0; 3; 7 | — |
| SECONDARY Number of Patients With High Carbonic Anhydrase 9 Expression at Baseline |
0; 4; 2 | — |
| SECONDARY Number of Patients With High VEGF-A Expression at Baseline |
2; 5; 16 | — |
| SECONDARY Number of Patients With High VEGF-R2 Expression at Baseline |
4; 4; 13 | — |
| SECONDARY Progression-free Survival Hazard Ratio by Hypoxia Inducible Factor-2alpha Expression |
1.36 | — |
| SECONDARY Progression-free Survival Hazard Ratio by Carbonic Anhydrase 9 (CA9) Expression |
0.705 | — |
| SECONDARY Progression-free Survival Hazard Ratio by VEGF-A Expression |
0.091 | — |
| SECONDARY Progression-free Survival Hazard Ratio by VEGF-R2 Expression |
0.632 | — |
Summary
This phase II trial is studying how well giving bevacizumab together with irinotecan works in treating young patients with recurrent, progressive, or refractory glioma, medulloblastoma, ependymoma, or low grade glioma. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of glioma by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with irinotecan may kill more tumor cells.
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed high-grade glioma (WHO grade III or IV) at any site within the brain, including the following:
- Anaplastic astrocytoma
- Glioblastoma multiforme (including giant cell and gliosarcoma subtypes)
- Anaplastic oligodendroglioma
- Anaplastic ganglioglioma
- Anaplastic oligoastrocytoma
- Diffuse brain stem glioma
- Histologic confirmation not required
- Histologically confirmed medulloblastoma
- Histologically confirmed ependymoma
- Primary spinal cord malignant glioma with measurable metastatic disease within the brain
- Histologic confirmation required
- Neuraxis dissemination allowed provided there is bidimensionally measurable disease within the brain and spinal cord
- Low grade glioma at any site within the brain with or without spinal cord disease
- Recurrent, progressive, or refractory disease (must have received prior chemoradiotherapy)
- No more than 2 prior chemotherapy regimens following relapse
- Bidimensionally measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 2 planes
- If there is spinal cord disease as well, response assessment will be based only upon the measurable tumor in the brain
- No diffuse gliomatosis cerebri with grade 2) within the past 2 weeks
- No central non-cerebellar PNET's (e.g., cerebral PNET or pineoblastoma)
- No spinal cord tumors only
- Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)
- Absolute neutrophil count ≥ 1,500/mm³ (unsupported)
- Platelet count ≥ 100,000/mm³ (unsupported)
- Hemoglobin > 8 g/dL (support allowed)
- Creatinine normal
- BUN 95th percentile for age
- No stroke, myocardial infarction, or unstable angina within the past 6 months
- No clinically significant peripheral vascular disease
- No significant traumatic injury within the past 6 weeks
- No evidence of bleeding diathesis, coagulopathy, or PT INR > 1.5
- Urine protein/creatinine ratio ≤ 1.0
- No abdominal fistula or gastrointestinal perforation within the past 6 months
- No serious nonhealing wound, ulcer, or bone fracture
- At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas)
- At least 7 days since prior investigational or biologic agents (3 weeks if patient experienced ≥ grade 2 myelosuppression or if agent has a prolonged half-life)
- More than 7 days since prior minor surgery
- More than 12 weeks since prior craniospinal or focal irradiation to primary tumor or other sites
- At least 4 weeks since prior major surgery and recovered
- At least 3 months since prior autologous bone marrow or stem cell transplantation
- At least 2 weeks since prior colony-forming growth factors (i.e., filgrastim [G-CSF], sargramostim [GM-CSF], epoetin alfa)
- No prior bevacizumab or irinotecan hydrochloride
- No anticipated surgery during treatment
- No concurrent prophylactic G-CSF, GM-CSF, or epoetin alfa
- Concurrent dexamethasone allowed provided the dose is stable or decreasing over the past week
- No other concurrent anticancer or investigational drugs
- No concurrent medications that may interfere with study (e.g., immunosuppressive agents other than corticosteroids)
- No concurrent therapeutic anticoagulation
- No concurrent nonsteroidal anti-inflammatory drugs, clopidogrel bisulfate, dipyridamole, or acetylsalicylic acid (aspirin) > 81 mg/day
Data sourced from ClinicalTrials.gov (NCT00381797). 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.