Phase 1
N=26
Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors
Central Nervous System Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00876993 ↗Enrolled (actual)
26
Serious AEs
30.8%
Results posted
Aug 2019
Primary outcome: Primary: Measurement of Number of Adverse Events — 4; 6; 3; 5 Adverse events
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Bevacizumab (Drug); Irinotecan (Drug); Temozolomide (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Johns Hopkins All Children's Hospital
- Primary completion
- Sep 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Measurement of Number of Adverse Events |
4; 6; 3; 5; 3; 4 | — |
| SECONDARY Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents. |
0; 0; 0; 1; 0; 1 | — |
| SECONDARY 2 Year Event Free Survival With Children Treated With This Regimen. |
4; 6; 3; 5; 3 | — |
| SECONDARY To Provide Safety and Efficacy Data for to Recommend Further Larger Studies. |
2; 0; 0; 1; 1; 0 | — |
Summary
Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
Eligibility Criteria
Inclusion Criteria
- Medulloblastomas, high-grade glioma, low-grade glioma, and ependymoma are eligible. Other central nervous system tumors may be considered for treatment at discretion of investigator. Pathology is required unless diffuse intrinsic pontine glioma or optic pathway tumor.
- The patient should have failed first line therapy and be considered refractory, relapsed, or recurrent. Exceptions are high grade gliomas including brain stem gliomas.
- Age 18 months though age 23 years are eligible for this protocol.
- The patient may have received any of the agents, but not in this combination. Patients will not be eligible if they have received the combination of bevacizumab and IV irinotecan as prior therapy. They will not be eligible if they had progressive disease on any of these agents. Investigator discretion may also be used.
- Bone marrow should be recovered from prior therapy with ANC >1500 and platelets >100,000.
- Serum creatinine should be less than institutional upper limit of norm.
- ALT/AST <3 times normal and bilirubin <1.5 times normal.
- Neurologic symptoms should be stable for 1 week with stable or decreasing doses of steroids.
- Patients should not be pregnant or breast feeding.
Exclusion Criteria
- Patients with bleeding disorders or on anticoagulants.
- Uncontrolled hypertension.
- Other risks of bleeding determined on individual basis.
- Patients receiving enzyme inducing anticonvulsants.
- Patients with significant cardiac or pulmonary dysfunction that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results.
- For patients receiving bevacizumab, those who have had surgical procedures should not receive bevacizumab within 28 days of a major procedure, 14 days of an intermediate procedure and 7 days of a minor procedure. Lumbar punctures or placement of PICC lines are not considered minor procedures and may occur at any time prior to or during therapy.
Data sourced from ClinicalTrials.gov (NCT00876993). 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.