- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00876993
Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors
A Phase I Study Of Irinotecan and Bevacizumab With Temozolomide in Children With Recurrent/Refractory Central Nervous System Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Bevacizumab dosing is 10 mg/kg on day 1 and day 15 of a 28 days course given IV.
Irinotecan dosing is 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the MTD of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150 mg/m2.
For dose level 0 Temozolomide, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO. Doses will be escalated according to standard phase I dose escalation criteria.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Saint Petersburg, Florida, United States, 33701
- Johns Hopkins All Children's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Level 0
Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 75 mg/m^2 PO
|
Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
Other Names:
Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels.
If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
Other Names:
For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course.
Doses will be escalated according to standard phase I dose escalation criteria.
Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
Other Names:
|
Experimental: Dose Level 1
Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 125 mg/m^2 PO
|
Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
Other Names:
Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels.
If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
Other Names:
For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course.
Doses will be escalated according to standard phase I dose escalation criteria.
Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
Other Names:
|
Experimental: Dose Level 2
Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 175 mg/m^2 PO
|
Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
Other Names:
Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels.
If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
Other Names:
For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course.
Doses will be escalated according to standard phase I dose escalation criteria.
Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
Other Names:
|
Experimental: Dose Level 3
Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 200 mg/m^2 PO
|
Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
Other Names:
Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels.
If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
Other Names:
For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course.
Doses will be escalated according to standard phase I dose escalation criteria.
Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
Other Names:
|
Experimental: Dose Level 4
Bevacizmuab 10 mg/kg IV Irinotecan 150 mg/m^2 IV Temozolomide 200 mg/m^2 PO
|
Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
Other Names:
Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels.
If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
Other Names:
For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course.
Doses will be escalated according to standard phase I dose escalation criteria.
Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measurement of Number of Adverse Events
Time Frame: Two 28-day cycles
|
Collect and grade the all of the adverse events to evaluate for safety.
This data was collected for the first 2 cycles for each participant.
|
Two 28-day cycles
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents.
Time Frame: Every 2 cycles up to 24 cycles
|
Best response by MRIs per definitions in the protocol (complete response, partial response, stable disease, progressive disease).
MRI's were obtained every 2 cycles and the best response was reported.
|
Every 2 cycles up to 24 cycles
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2 Year Event Free Survival With Children Treated With This Regimen.
Time Frame: 2 year
|
2 year actual event free survival.with
children treated with this protocol
|
2 year
|
To Provide Safety and Efficacy Data for to Recommend Further Larger Studies.
Time Frame: Two 28 day cycles
|
Number participants with grade 3 and 4 hematologic and non-hematologic toxicities.
All toxicities are for end of cycle 2.
|
Two 28 day cycles
|
Collaborators and Investigators
Investigators
- Principal Investigator: Stacie Stapleton, MD, Johns Hopkins All Children's Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Topoisomerase I Inhibitors
- Temozolomide
- Bevacizumab
- Irinotecan
Other Study ID Numbers
- ACH-CNS-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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