Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors

• Sponsor: Johns Hopkins All Children's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00876993
• Collaborator: The V Foundation (Other), Brain Tumor Alliance (Other)
• Enrollment: 26
• Location: 1
• Arms: 5
• Duration (Months): 84
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Central Nervous System Tumors	Drug: Bevacizumab; Drug: Irinotecan; Drug: Temozolomide	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study Of Irinotecan and Bevacizumab With Temozolomide in Children With Recurrent/Refractory Central Nervous System Tumors
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Level 0 Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 75 mg/m^2 PO	Drug: Bevacizumab; Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle; Other Names: Irinotecan and temozolomide ; Drug: Irinotecan; 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: Bevacizumab and temozolomide ; Drug: Temozolomide; 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: Bevacizumab and irinotecan
Experimental: Dose Level 1 Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 125 mg/m^2 PO	Drug: Bevacizumab; Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle; Other Names: Irinotecan and temozolomide ; Drug: Irinotecan; 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: Bevacizumab and temozolomide ; Drug: Temozolomide; 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: Bevacizumab and irinotecan
Experimental: Dose Level 2 Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 175 mg/m^2 PO	Drug: Bevacizumab; Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle; Other Names: Irinotecan and temozolomide ; Drug: Irinotecan; 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: Bevacizumab and temozolomide ; Drug: Temozolomide; 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: Bevacizumab and irinotecan
Experimental: Dose Level 3 Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m^2 IV Temozolomide 200 mg/m^2 PO	Drug: Bevacizumab; Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle; Other Names: Irinotecan and temozolomide ; Drug: Irinotecan; 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: Bevacizumab and temozolomide ; Drug: Temozolomide; 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: Bevacizumab and irinotecan
Experimental: Dose Level 4 Bevacizmuab 10 mg/kg IV Irinotecan 150 mg/m^2 IV Temozolomide 200 mg/m^2 PO	Drug: Bevacizumab; Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle; Other Names: Irinotecan and temozolomide ; Drug: Irinotecan; 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: Bevacizumab and temozolomide ; Drug: Temozolomide; 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: Bevacizumab and irinotecan

Outcome Measures

Primary Outcome Measures

1. Measurement of Number of Adverse Events [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.

Secondary Outcome Measures

1. Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents. [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.

2. 2 Year Event Free Survival With Children Treated With This Regimen. [2 year]

   2 year actual event free survival.with children treated with this protocol

3. To Provide Safety and Efficacy Data for to Recommend Further Larger Studies. [Two 28 day cycles]

   Number participants with grade 3 and 4 hematologic and non-hematologic toxicities. All toxicities are for end of cycle 2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Months to 23 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701

Sponsors and Collaborators

• Johns Hopkins All Children's Hospital
• The V Foundation
• Brain Tumor Alliance

Investigators

• Principal Investigator: Stacie Stapleton, MD, Johns Hopkins All Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Stacie Stapleton, MD, Director, Pediatric Neuro-Oncology Program, Johns Hopkins All Children's Hospital
• ClinicalTrials.gov Identifier: NCT00876993
• Other Study ID Numbers: ACH-CNS-001
• First Posted: Apr 7, 2009
• Last Update Posted: Jun 5, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Bevacizumab; Irinotecan; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Cohort 1 - Dose Level 1	Cohort 2 - Dose Level 0	Cohort 3 - Dose Level 1	Cohort 4 - Dose Level 2	Cohort 5 - Dose Level 1
Arm/Group Description	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 75 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 175 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle
Period Title: Overall Study
STARTED	5	6	5	5	5
COMPLETED	4	6	3	5	3
NOT COMPLETED	1	0	2	0	2

Baseline Characteristics

Arm/Group Title	Cohort 1 - Dose Level 1	Cohort 2 - Dose Level 0	Cohort 3 - Dose Level 1	Cohort 4 - Dose Level 2	Cohort 5 - Dose Level 1	Total
Arm/Group Description	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 75 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 175 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Total of all reporting groups
Overall Participants	5	6	5	5	5	26
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	9.2	8.5	11.4	9.8	10.6	9.8
Sex: Female, Male (Count of Participants)
Female	2 40%	1 16.7%	3 60%	2 40%	0 0%	8 30.8%
Male	3 60%	5 83.3%	2 40%	3 60%	5 100%	18 69.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 20%	0 0%	1 20%	0 0%	0 0%	2 7.7%
Not Hispanic or Latino	2 40%	1 16.7%	3 60%	4 80%	3 60%	13 50%
Unknown or Not Reported	2 40%	5 83.3%	1 20%	1 20%	2 40%	11 42.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 16.7%	0 0%	0 0%	1 20%	2 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 33.3%	2 40%	1 20%	1 20%	6 23.1%
White	5 100%	2 33.3%	3 60%	3 60%	3 60%	16 61.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 16.7%	0 0%	1 20%	0 0%	2 7.7%
Region of Enrollment (Count of Participants)
United States	5 100%	6 100%	5 100%	5 100%	5 100%	26 100%
Diagnosis (Count of Participants)
Medulloblastoma	0 0%	0 0%	1 20%	0 0%	1 20%	2 7.7%
High Grade Glioma	3 60%	2 33.3%	2 40%	2 40%	2 40%	11 42.3%
Low Grade Glioma	1 20%	1 16.7%	1 20%	2 40%	1 20%	6 23.1%
Choroid Plexus Tumors	1 20%	0 0%	0 0%	0 0%	0 0%	1 3.8%
Ependymoma	0 0%	2 33.3%	0 0%	0 0%	0 0%	2 7.7%
PNET	0 0%	1 16.7%	0 0%	1 20%	1 20%	3 11.5%
Other	0 0%	0 0%	1 20%	0 0%	0 0%	1 3.8%

Outcome Measures

1. Primary Outcome

Title	Measurement of Number of Adverse Events
Description	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.
Time Frame	Two 28-day cycles

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Dose Level 1	Cohort 2 - Dose Level 0	Cohort 3 - Dose Level 1	Cohort 4 - Dose Level 2	Cohort 5 - Dose Level 1
Arm/Group Description	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 75 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	BBevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 175 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle
Measure Participants	4	6	3	5	3
Grade 1 adverse events	4	6	3	5	3
Grade 2 adverse events	4	3	3	5	2
Grade 3 adverse events	3	1	1	4	1
Grade 4 adverse events	1	0	0	0	0

2. Secondary Outcome

Title	Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents.
Description	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.
Time Frame	Every 2 cycles up to 24 cycles

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Dose Level 1	Cohort 2 - Dose Level 0	Cohort 3 - Dose Level 1	Cohort 4 - Dose Level 2	Cohort 5 - Dose Level 1
Arm/Group Description	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 75 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 175 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle
Measure Participants	4	6	3	5	3
Complete Response	0 0%	0 0%	0 0%	1 20%	0 0%
Partial Response	1 20%	1 16.7%	1 20%	3 60%	0 0%
Stable Disease	3 60%	3 50%	0 0%	1 20%	3 60%
Progressive Disease	0 0%	2 33.3%	2 40%	0 0%	0 0%

3. Secondary Outcome

Title	2 Year Event Free Survival With Children Treated With This Regimen.
Description	2 year actual event free survival.with children treated with this protocol
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Dose Level 1	Cohort 2 - Dose Level 0	Cohort 3 - Dose Level 1	Cohort 4 - Dose Level 2	Cohort 5 - Dose Level 1
Arm/Group Description	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 75 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 175 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle
Measure Participants	4	6	3	5	3
Number [Count of participants]	4 80%	6 100%	3 60%	5 100%	3 60%

4. Secondary Outcome

Title	To Provide Safety and Efficacy Data for to Recommend Further Larger Studies.
Description	Number participants with grade 3 and 4 hematologic and non-hematologic toxicities. All toxicities are for end of cycle 2.
Time Frame	Two 28 day cycles

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Dose Level 1	Cohort 2 - Dose Level 0	Cohort 3 - Dose Level 1	Cohort 4 - Dose Level 2	Cohort 5 - Dose Level 1
Arm/Group Description	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 75 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 175 mg/m^2 PO days 1-5 28 day cycle	BBevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle
Measure Participants	4	6	3	5	3
Grade 3 & 4 Blood/Bone Marrow	2 40%	0 0%	0 0%	1 20%	1 20%
Grade 3 & 4 Gastrointestinal	0 0%	0 0%	1 20%	1 20%	0 0%
Grade 3 & 4 Metabolic/Laboratory	0 0%	0 0%	0 0%	1 20%	0 0%
Grade 3 & 4 Musculoskelatal/Soft Tissue	0 0%	0 0%	0 0%	1 20%	0 0%
Grade 3 & 4 Neurology	1 20%	0 0%	0 0%	3 60%	0 0%
Grade 3 & 4 Pain	1 20%	0 0%	0 0%	2 40%	0 0%
Grade 3 & 4 Vascular	0 0%	1 16.7%	0 0%	0 0%	0 0%
Grade 3 & 4 Other	1 20%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Two 28 day cycles for each participant
Arm/Group Title	Cohort 1 - Dose Level 1		Cohort 2 - Dose Level 0		Cohort 3 - Dose Level 1		Cohort 4 - Dose Level 2		Cohort 5 - Dose Level 1
Arm/Group Description	Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle		Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 75 mg/m^2 PO days 1-5 28 day cycle		Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle		Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 175 mg/m^2 PO days 1-5 28 day cycle		Bevacizmuab 10 mg/kg IV days 1 and 15 Irinotecan 125 mg/m^2 IV days 1 and 15 Temozolomide 125 mg/m^2 PO days 1-5 28 day cycle
All Cause Mortality
	Cohort 1 - Dose Level 1		Cohort 2 - Dose Level 0		Cohort 3 - Dose Level 1		Cohort 4 - Dose Level 2		Cohort 5 - Dose Level 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1 - Dose Level 1		Cohort 2 - Dose Level 0		Cohort 3 - Dose Level 1		Cohort 4 - Dose Level 2		Cohort 5 - Dose Level 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/6 (16.7%)		1/5 (20%)		4/5 (80%)		1/5 (20%)
Blood and lymphatic system disorders
Hemolytic anemia	0/5 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/5 (20%)	1
Gastrointestinal disorders
GI illness	0/5 (0%)	0	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0
Vomiting	0/5 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Injury, poisoning and procedural complications
Injury	0/5 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	2/5 (40%)	2	0/5 (0%)	0
Nervous system disorders
Neurology, other - pneumocephalus	1/5 (20%)	1	0/6 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Neurologic deficits	0/5 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Shunt malfunction	0/5 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	2/5 (40%)	2	0/5 (0%)	0
Dystonic reaction	0/5 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Vascular disorders
Thrombus - embolism	0/5 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort 1 - Dose Level 1		Cohort 2 - Dose Level 0		Cohort 3 - Dose Level 1		Cohort 4 - Dose Level 2		Cohort 5 - Dose Level 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		1/6 (16.7%)		2/5 (40%)		3/5 (60%)		3/5 (60%)
Blood and lymphatic system disorders
Leukocytes	2/5 (40%)	2	0/6 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Neutrophils	2/5 (40%)	2	0/6 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	2/5 (40%)	2
Lymphocytes	1/5 (20%)	1	0/6 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/5 (0%)	0
Thrombus	0/5 (0%)	0	1/6 (16.7%)	1	0/5 (0%)	0	0/5 (0%)	0	0/5 (0%)	0
Gastrointestinal disorders
Vomiting	0/5 (0%)	0	0/6 (0%)	0	1/5 (20%)	1	1/5 (20%)	1	0/5 (0%)	0
ALT/AST	0/5 (0%)	0	0/6 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/5 (0%)	0
Nervous system disorders
Pain	1/5 (20%)	1	0/6 (0%)	0	0/5 (0%)	0	2/5 (40%)	2	0/5 (0%)	0
Syncope/Seizure	1/5 (20%)	1	0/6 (0%)	0	0/5 (0%)	0	3/5 (60%)	3	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.